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12,900 | 28,477,396 | In general , our study demonstrated that statins might have beneficial effects on reducing albuminuria in diabetic kidney disease patients .
However , there was no strong evidence that the same intervention had an effect on overt proteinuria or eGFR outcomes in these patients | Summary The effects of statins on renal outcomes in patients with diabetic kidney disease were conflicting .
The aim of the study was to investigate whether statins treatment could affect renal outcomes ( albuminuria or proteinuria , estimated glomerular filtration rate [ eGFR ] ) for diabetic kidney disease patients . | INTRODUCTION Diabetic Nephropathy ( DN ) is one of the main complications of diabetes mellitus , mostly ending to end-stage renal disease . Leptin and C-reactive protein ( CRP ) , as inflammatory markers implicated in the progression of DN , increase in diabetes mellitus , while transferrin and albumin , as members of anti-oxidant defense mechanism , are found to decline . MATERIAL S AND METHODS In a controlled clinical trial , 65 patients with type 2 DN were assigned to receive lovastatin or placebo , for 3 months , to assess statins ' impact on serum levels of leptin , CRP , transferrin , albumin , and lipid profile . RESULTS Serum levels of CRP ( 3.52 + /- 4.16 mg/dL to 2.84 + /- 3.06 mg/dL , P = .02 ) , leptin ( 10.78 + /- 8.30 mg/dL to 7.80 + /- 5.41 mg/dL , P = .006 ) , low-density lipoprotein cholesterol ( 116.16 + /- 46.54 mg/dL to 85.46 + /- 29.22 mg/dL , P = .001 ) , and total cholesterol ( 199.00 + /- 43.33 mg/dL to 164.67 + /- 35.19 mg/dL , P = .001 ) were lowered after lovastatin therapy . Mean serum level of high-density lipoprotein cholesterol increased ( 40.00 mg/dL to 42.80 mg/dL , P = .005 ) after the treatment . Lovastatin had no significant effect on albumin and transferrin . Placebo did not change any of the parameters after 3 months . CONCLUSIONS The effect of statins on the inflammatory markers involved in the development of DN is a new approach to evidence supporting the pleiotropic effect of this drug group Summary The effect of simvastatin ( 10–20 mg/day ) on kidney function , urinary albumin excretion rate and insulin sensitivity was evaluated in 18 Type 2 ( non-insulin-dependent ) diabetic patients with microalbuminuria and moderate hypercholesterolaemia ( total cholesterol ≥5.5 mmol·l−1 ) . In a double-blind , r and omized and placebo-controlled design treatment with simvastatin ( n=8 ) for 36 weeks significantly reduced total cholesterol ( 6.7±0.3 vs 5.1 mmol·l−1 ( p<0.01 ) ) , LDL-cholesterol ( 4.4±0.3 vs 2.9±0.2 mmol·l−1 ( p<0.001 ) ) and apolipoprotein B ( 1.05±0.04 vs 0.77±0.02 mmol·l−1 ( p<0.01 ) ) levels as compared to placebo ( n=10 ) . Both glomerular filtration rate ( mean±SEM ) ( simvastatin : 96.6±8.0 vs 96.0±5.7 ml·min−1·1.73 m−2 , placebo : 97.1±6.7 vs 88.8±6.0 ml·min−1·1.73 m−2 ) ( NS ) and urinary albumin excretion rate ( geometric mean x/÷ antilog SEM ) ( simvastatin : 18.4x/÷1.3vs 16.2 x/÷1.2 μg·min−1 , placebo 33.1 x/÷ 1.3 vs 42.7 x/÷ 1.3 μg·min−1)(NS ) were unchanged during the study . A euglycaemic hyperinsulinaemic clamp was performed at baseline and after 18 weeks in seven simvastatin- and nine placebo-treated patients . Isotopically determined basal and insulin-stimulated glucose disposal was similarly reduced before and during therapy in both the simvastatin ( 2.0±0.1 vs 1.9±0.1 ( NS ) and 3.1±0.6 vs 3.1±0.7 mg·kg−1·min−1 ( NS ) ) and the placebo group ( 1.9±0.1 vs 1.8±0.1 ( NS ) and 4.1±0.6 vs 3.8±0.2 mg·kg−1·min−1 ( NS ) ) . No different was observed in glucose storage or glucose and lipid oxidation before and after treatment . Further , the suppression of hepatic glucose production during hyperinsulinaemia was not influenced by simvastatin ( −0.7±0.8 vs −0.7±0.5 mg·kg−1·min−1 ( NS ) ) . In conclusion , despite marked improvement in the dyslipidaemia simvastatin had no impact on kidney function or urinary albumin excretion rate and did not reduce insulin resistance in these microalbuminuric and moderately hypercholesterolaemic Type 2 diabetic patients AIM We aim ed to assess the effects of rosuvastatin treatment on lipid levels , a biomarker of oxidative stress , albuminuria , and kidney function in patients with diabetic nephropathy . METHODS We conducted a prospect i ve , open-label , parallel group , controlled study of 104 patients with diabetic nephropathy , low-density lipoprotein cholesterol ( LDL-C ) levels of > 120 mg/dL , and well-controlled blood pressure who were undergoing treatment with renin angiotensin system inhibitors . Patients were r and omly assigned to two groups : the rosuvastatin group ( n = 52 ; 2.5 mg/day rosuvastatin , increased to 10 mg/day ) and the control group ( n = 52 ; no rosuvastatin administered ) . We determined the efficacy of rosuvastatin by monitoring serum lipid profiles , high sensitivity C-reactive protein ( hs-CRP ) , malondialdehyde-modified LDL ( MDA-LDL ) , and cystatin C levels . In addition , urinary albumin , 8-hydroxydeoxyguanosine ( 8-OHdG ) and liver-type fatty acid-binding protein ( L-FABP ) levels were measured before and 6 months after rosuvastatin was added to the treatment . RESULTS Rosuvastatin effectively reduced total cholesterol , LDL-C , triglycerides , non-high-density lipoprotein cholesterol ( non-HDL-C ) levels , and the LDL-C/ HDL-C ratio in the rosuvastatin group . These parameters remained unchanged in patients who were not treated with rosuvastatin . Although there was no significant change in the estimated glomerular filtration rate level , serum cystatin C levels and urinary albumin excretion rates were significantly decreased in the rosuvastatin group . In addition , rosuvastatin significantly reduced hs-CRP and MDA-LDL levels . Moreover , urinary 8-OHdG and L-FABP levels at baseline ( 13.5±5.1 and 41.7±26.1 ng/mgCr , respectively ) decreased significantly at 6 months ( 11.5±4.0 and 26.9±13.4 ng/mgCr , respectively ) , and there was a significant correlation ( r = 0.48 , p < 0.01 ) . Multivariate analysis revealed that albuminuria was significantly correlated with only rosuvastatin use ( p = 0.0006 , R(2)= 0.53 ) . CONCLUSION Rosuvastatin administration reduced albuminuria , oxidative stress , and serum cystatin C levels , independent of blood pressure and lipid levels OBJECTIVE Liver-type fatty acid-binding protein ( l-FABP ) is expressed in renal proximal tubules and is reported to be a useful marker for progression of chronic glomerulonephritis . The aim of this study was to determine whether urinary l-FABP levels are altered at various stages of diabetic nephropathy and whether pitavastatin affects urinary l-FABP levels in early diabetic nephropathy . RESEARCH DESIGN AND METHODS Fifty-eight patients with type 2 diabetes ( 34 men and 24 women , median age 52 years ) and 20 healthy , age-matched subjects ( group E ) were recruited for the study . The diabetic patients included 12 patients without nephropathy ( group A ) , 20 patients with microalbuminuria ( group B ) , 14 patients with macroalbuminuria and normal renal function ( group C ) , and 12 patients with chronic renal failure but not undergoing hemodialysis ( blood creatinine > 1.2 mg/dl ; mean 2.5 mg/dl , group D ) . Twenty group B patients were r and omly assigned to receive 1 mg/day pitavastatin ( 10 patients , group B1 ) or placebo ( 10 patients , group B2 ) . Treatment was continued for 12 months . Urinary l-FABP levels were measured by enzyme-linked immunosorbent assay . Urinary 8-hydroxydeoxyguanosine and serum free fatty acids ( FFAs ) were also measured in group B. RESULTS Urinary l-FABP levels in groups A-D were 6.2 + /- 4.6 microg/g creatinine , 19.6 + /- 13.5 microg/g creatinine , 26.8 + /- 20.4 microg/g creatinine , and 52.4 + /- 46.8 microg/g creatinine , respectively . Urinary l-FABP levels in groups B-D were significantly higher than those in healthy subjects ( group E , 5.8 + /- 4.0 microg/g creatinine ) ( group B , P < 0.05 ; group C , P < 0.01 ; group D , P < 0.01 ) . In group B1 , urinary albumin excretion ( UAE ) and urinary l-FABP levels were decreased after pitavastatin treatment ( UAE before , 110 + /- 74 microg/min ; 6 months , 88 + /- 60 microg/min , P < 0.05 ; 12 months , 58 + /- 32 microg/min , P < 0.01 ; l-FABP before , 18.6 + /- 12.5 microg/g creatinine ; 6 months , 12.2 + /- 8.8 microg/g creatinine , P < 0.05 ; 12 months , 8.8 + /- 6.4 microg/g creatinine , P < 0.01 ) . In group B2 , UAE and l-FABP levels showed little change during the experimental period . In group B1 , urinary 8-hydroxydeoxyguanosine was decreased 12 months after pitavastatin treatment ( before 32.5 + /- 19.5 ng/mg creatinine , after 18.8 + /- 14.5 ng/mg creatinine , P < 0.01 ) , but in group B2 , these showed little difference during the experimental period . In both groups B1 and B2 , serum FFAs showed little difference during the experimental period . CONCLUSIONS Urinary l-FABP levels appear to be associated with the progression of diabetic nephropathy , and pitavastatin may be effective in ameliorating tubulointerstitial damage in early diabetic nephropathy Background / Aims : To determine whether cerivastatin , a newly developed novel synthetic potent statin , exerts a renoprotective effect , we assessed urinary albumin excretion ( UAE ) and plasma and urinary endothelin (ET)-1 concentrations in normotensive microalbuminuric type 2 diabetes patients with dyslipidemia . Methods : Sixty normotensive type 2 diabetic patients ( 38 men and 22 women ; mean age 56.5 years ) with microalbuminuria ( 20–200 µg/min ) and dyslipidemia ( total cholesterol > 200 mg/dl , LDL cholesterol > 160 mg/dl , HDL cholesterol < 35 mg/dl , and triglyceride > 150 mg/dl ) were enrolled in a double-blind study for 6 months , receiving either cerivastatin ( 0.15 mg/day ) or placebo . Plasma and urinary ET-1 concentrations were measured by radioimmunoassay . Results : Cerivastatin did not affect serum creatinine and HbA1c levels , and reduced systolic blood pressure slightly , but not significantly . Plasma levels of total cholesterol and LDL cholesterol were significantly reduced ( p < 0.01 ) , and plasma triglyceride levels were also reduced significantly ( p < 0.05 ) after 6 months of cerivastatin treatment . A concomitant significant decrease in UAE ( p < 0.01 ) , and urinary and plasma ET-1 concentrations ( p < 0.01 ) were found during this period . Conclusion : The use of cerivastatin is associated with decreased microalbuminuria and plasma and urinary ET-1 levels in microalbuminuric patients with type 2 diabetic mellitus and speculate that this may represent an amelioration of renal injury The effects of pravastatin on plasma lipid levels , in vitro oxidizability of the non-HDL fraction , metabolic control , urinary albumin excretion , and four serum enzymes ( SGPT , SGOT , GT and CPK ) were studied in 20 insulin-dependent diabetic patients ( IDDM ) with incipient nephropathy . The patients were divided into two groups and the study was carried out by a crossover design . After 12 weeks pravastatin treatment ( 20 mg daily ) , plasma cholesterol , LDL-cholesterol and apolipoprotein B ( Apo B ) decreased by 22 , 19 and 15 % , respectively . The thiobarbituric acid reactive substances ( TBARS ) formation and the oxidation lagtime of the non-HDL fraction during the in vitro incubation with copper were not changed before and after treatment . The HbA1c and blood glucose levels , urinary albumin excretion , SGOT , SGPT and GT were not influenced by pravastatin treatment . CPK activity was elevated after 12 weeks of pravastatin treatment , and this elevation persisted even after the 12 weeks placebo period . So , pravastatin could be used as an effective drug for IDDM patients with incipient nephropathy , but close monitoring of the CPK activity is recommended Summary The aim of this study was to assess the effect of simvastatin on plasma lipoproteins and renal function in hypercholesterolaemic Type 1 ( insulin-dependent ) diabetic patients with diabetic nephropathy . Twenty-six hypercholesterolaemic ( total cholesterol ≽ 5.5 mmol/l ) Type 1 diabetic patients with nephropathy were enrolled in a double-blind r and omized placebo-controlled study for 12 weeks . The active treatment group ( n -14 ) received simvastatin ( 10–20 mg/day ) for 12 weeks while the remaining 12 patients received treatment with placebo . The results during simvastatin treatment ( baseline vs 12 weeks ) : total cholesterol 6.6 vs 4.8 mmol/1 ( p < 0.01 ) , LDL-cholesterol 4.25 vs 2.57 mmol/l ( p < 0.01 ) and apolipoprotein B 1.37 vs 1.06 mmol/l ( p < 0.01 ) . HDL-cholesterol , and apolipoprotein A-I remained unchanged . Total cholesterol , LDL-cholesterol , HDL-cholesterol , apolipoprotein A – I , apolipoprotein B remained unchanged during placebo treatment . Albuminuria measured during the simvastatin and the placebo treatment ( baseline vs 12 weeks ) ( the data are logarithmically transformed before analysis because of their positively skewed transformation ; geometric mean ( ×/÷ antilog SE ) is indicated ) was 458 ( ×/÷ 1.58 ) vs 393 ( ×/÷ 1.61 ) and 481 ( ×/÷ 1.62 ) vs 368 ( ×/÷ 1.78 μg/min ( NS ) . Glomerular filtration rate during simvastatin and placebo treatment ( baseline vs 12 weeks ) was 64 vs 63 and 72 vs 74 ml·min−1·1.73 m−2 , respectively . Two patients receiving simvastatin treatment were withdrawn , one due to gastrointestinal side effects and one due to myalgia . In conclusion , our short-term study in Type 1 diabetic patients with diabetic nephropathy did not reveal any beneficial effect on albuminuria despite a striking lipid-lowering effect of simvastatin in diabetic nephropathy OBJECTIVE To study the long-term effects of simvastatin on urinary albumin excretion rate ( AER ) in normotensive microalbuminuric type 2 diabetic patients with hypercholesterolemia . RESEARCH DESIGN AND METHODS A total of 19 normotensive microalbuminuric hypercholesterolemic type 2 diabetic patients entered a double-blind crossover study for 2 years , receiving either simvastatin ( 20 mg/day ) or placebo ( each treatment for 1 year ) . RESULTS Simvastatin significantly decreased plasma cholesterol ( total and LDL ) after 52 weeks of treatment . A concomitant significant decrease of AER ( 25 % from basal ) with no significant changes in creatinine clearance was observed during the same period . CONCLUSIONS Our data are in keeping with the hypothesis that simvastatin might be used as an additional means to preserve renal function in microalbuminuric hypercholesterolemic type 2 diabetic patients correlates of prevalent coronary calcification . Int J Cardiol 2005 ; 98 : 325–330 45 . Shisen J , Leung DY , Juergens CP . Gender and age differences in the prevalence of coronary artery calcification in 953 Chinese subjects . Hearth Lung Circ 2005 ; 14 : 69–73 46 . London GM , Marchais SJ , Guerin AP et al. Association of bone activity , calcium load , aortic stiffness , and calcifications in ESRD . J Am Soc Nephrol 2008 ; 19 : 1827–1835 47 . Kidney Disease : Improving Global Outcomes ( KDIGO ) CKD-MBD Work Group . KDIGO Clinical Practice Guideline for the Diagnosis , Evaluation , Prevention , and Treatment of Chronic Kidney DiseaseMineral and Bone Disorder ( CKD-MBD ) . Kidney Int Suppl 2009 ; 113 : S1–S130 48 . Stenvinkel P , Wang K , Qureshi AR et al. Low fetuin-A levels are associated with cardiovascular death : impact of variations in the gene encoding fetuin . Kidney Int 2005 ; 67 : 2383–2392 49 . Chiu YW , Teitelbaum I , Misra M et al. Pill burden , adherence , hyperphosphatemia , and quality of life in maintenance dialysis patients . Clin J Am Soc Nephrol 2009 ; 4 : 1089–1096 50 . Giachelli CM . The emerging role of phosphate in vascular calcification . Kidney Int 2009 ; 75 : 890–897 51 . Fan S , Ross C , Mitra S et al. A r and omized , crossover design study of sevelamer carbonate powder and sevelamer hydrochloride tablets in chronic kidney disease patients on haemodialysis . Nephrol Dial Transplant 2009 ; 24 : 3794–3799 52 . Fishbane S , Delmez J , Suki WN et al. A r and omized , parallel , openlabel study to compare once-daily sevelamer carbonate powder dosing with thrice-daily sevelamer hydrochloride tablet dosing in CKD patients on hemodialysis . Am J Kidney Dis 2010 ; 55 : 307–315 53 . Oliveira RB , Cancela AL , Graciolli FG et al. Early control of PTH and FGF23 in normophosphatemic CKD patients : a new target in CKD-MBD therapy ? . Clin J Am Soc Nephrol 2010 ; 5 : 286–291 54 . Br and enburg VM , Jahnen-Dechent W , Ketteler M. Sevelamer and the bone-vascular axis in chronic kidney disease : bone turnover , inflammation , and calcification regulation . Kidney Int Suppl 2009 ; 114 : BACKGROUND The role of lipid-lowering treatments in renoprotection for patients with diabetes is debated . We studied the renal effects of two statins in patients with diabetes who had proteinuria . METHODS PLANET I was a r and omised , double-blind , parallel-group trial done in 147 research centres in Argentina , Brazil , Bulgaria , Canada , Denmark , France , Hungary , Italy , Mexico , Romania , and the USA . We enrolled patients with type 1 or type 2 diabetes aged 18 years or older with proteinuria ( urine protein : creatinine ratio [ UPCR ] 500 - 5000 mg/g ) and taking stable angiotensin-converting enzyme inhibitors , angiotensin receptor blockers , or both . We r and omly assigned participants to atorvastatin 80 mg , rosuvastatin 10 mg , or rosuvastatin 40 mg for 52 weeks . The primary endpoint was change from baseline to week 52 of mean UPCR in each treatment group . The study is registered with Clinical Trials.gov , number NCT00296374 . FINDINGS We enrolled 353 patients : 118 were assigned to rosuvastatin 10 mg , 124 to rosuvastatin 40 mg , and 111 to atorvastatin 80 mg ; of these , 325 were included in the intention-to-treat population . UPCR baseline : week 52 ratio was 0·87 ( 95 % CI 0·77 - 0·99 ; p=0·033 ) with atorvastatin 80 mg , 1·02 ( 0·88 - 1·18 ; p=0·83 ) with rosuvastatin 10 mg , and 0·96 ( 0·83 - 1·11 ; p=0·53 ) with rosuvastatin 40 mg . In a post-hoc analysis to compare statins , we combined data from PLANET I with those from PLANET II ( a similar r and omised parallel study of 237 patients with proteinuria but without diabetes ; registered with Clinical Trials.gov , NCT00296400 ) . In this analysis , atorvastatin 80 mg lowered UPCR significantly more than did rosuvastatin 10 mg ( -15·6 % , 95 % CI -28·3 to -0·5 ; p=0·043 ) and rosuvastatin 40 mg ( -18·2 % , -30·2 to -4·2 ; p=0·013 ) . Adverse events occurred in 69 ( 60 % ) of 116 patients in the rosuvastatin 10 mg group versus 79 ( 64 % ) of 123 patients in the rosuvastatin 40 mg group versus 63 ( 57 % ) of 110 patients in the atorvastatin 80 mg group ; renal events occurred in nine ( 7·8 % ) versus 12 ( 9·8 % ) versus five ( 4·5 % ) . INTERPRETATION Despite high-dose rosuvastatin lowering plasma lipid concentrations to a greater extent than did high-dose atorvastatin , atorvastatin seems to have more renoprotective effects for the studied chronic kidney disease population . FUNDING AstraZeneca |
12,901 | 30,198,405 | No significant intergroup difference was observed in the pain score on the first postoperative day or the incidence of perioperative adverse events .
Conclusions Compared with conventional analgesia , SPI-guided analgesia can reduce intraoperative opioid consumption and facilitate extubation .
Moreover , no intergroup difference was observed in the degree of postoperative pain or incidence of perioperative adverse events | Objective Previous studies comparing surgical pleth index (SPI)-guided and conventional analgesia have shown differing results .
Therefore , we compared the intraoperative opioid requirement , extubation time , postoperative pain scores , and perioperative adverse events between these two modalities . | BACKGROUND Surgical noxious stimuli generate a stress response with an increased sympathetic activity , potentially affecting the perioperative outcome . Surgical Pleth Index ( SPI ) , derived from the pulse plethysmogram , has been proposed as a tool to assess nociception-antinociception balance . The relationship between SPI and autonomic nervous system ( ANS ) during general anesthesia is poorly understood and it is doubtful if SPI-guided analgesia may offer advantages over the st and ard clinical practice . The study was design ed to evaluate if SPI-guided analgesia leads to a lower sympathetic modulation compared with st and ard clinical practice . METHODS Electrocardiographic wave , non-invasive blood pressure and SPI were recorded in ASA I-II patients undergoing elective laparoscopic cholecystectomy , r and omized to receive SPI-guided analgesia or st and ard analgesia . Hemodynamic parameters , SPI , mean and variance of heart rate , low ( LF ) and high frequency ( HF ) spectral components of heart rate variability were measured at four time points : ( T0 ) baseline , ( T1 ) after induction of general anesthesia , ( T2 ) after pneumoperitoneum insufflation and ( T3 ) after pneumoperitoneum withdrawal . RESULTS SPI , hemodynamic and ANS parameters changed significantly in both groups during the study period ( P<0.0001 ) . At T2 SPI and markers of sympathetic modulation were significantly lower in SPI group ( mean [ SD ] SPI 38.1 [ 15.3 ] vs. 48.1 [ 16.2 ] normalized units , P<0.05 ; LF 38 [ 8.6 ] vs. 56.2 [ 20.6 ] normalized units , P<0.01 ; LF/HF 1.01 [ 1.1 ] vs. 2.68 [ 2.07 ] , P<0.01 ) . There was no difference in remifentanil consumption , recovery time from anesthesia , or postoperative pain and complications . CONCLUSION SPI-guided analgesia led to a more stable sympathetic modulation but did n't seem to offer clinical ly relevant advantages over the st and ard clinical practice for laparoscopic cholecystectomy Background : Surgical stress index ( SSI ) , a novel multivariate index , has recently been proven to react well to surgical nociceptive stimuli and analgesic drug concentration changes during general anesthesia . We investigated the feasibility of application of SSI for guidance of remifentanil administration during propofol – remifentanil anesthesia . Methods : Eighty patients scheduled for elective ear – nose – throat surgery were r and omized into two groups , SSI-guided analgesia group ( SSI group ) and st and ard practice analgesia group ( control group ) . In both groups , anesthesia was maintained with a propofol target-controlled infusion and adjusted stepwise by 0.5 & mgr;g/ml to keep bispectral index values between 40 and 60 . In the SSI group , the predicted effect-site concentration of remifentanil was adjusted stepwise by 1 ng/ml to keep SSI values between 20 and 50 , whereas in the control group , predicted effect-site concentration of remifentanil was adjusted according to traditional inadequate analgesia criteria . Anesthetics consumption , recovery times , and incidence of unwanted events were recorded . Results : Remifentanil consumption ( average normalized infusion rate ) was lower in the SSI group than in the control group ( mean ± SD , 9.5 ± 3.8 & mgr;g · kg−1 · h−1 vs. 12.3 ± 5.2 & mgr;g · kg−1 · h−1 ; P < 0.05 ) . The number of unwanted events was less in the SSI group ( 84 ) than in the control group ( 556 ; P < 0.01 ) . Recovery times were comparable between groups . No patient reported intraoperative recall . Conclusions : SSI-guided anesthesia result ed in lower remifentanil consumption , more stable hemodynamics , and a lower incidence of unwanted events BACKGROUND Autonomic nervous system ( ANS ) sensitively responds to intraoperative stress . Several indices characterizing the state and responses of autonomic signs to nociceptive stimuli have been introduced . This study evaluated the behaviour of ANS descriptors after induction , before and during tracheal intubation , and during bilateral tonsillectomies after r and om and blinded unilateral infiltration of lidocaine 1 % until emergence from anaesthesia . METHODS Twelve patients undergoing bilateral tonsillectomy were anaesthetized with fentanyl and propofol ( induction ) and sevoflurane ( maintenance ) . All patients were monitored throughout anaesthesia for middle finger temperature , non-invasive arterial pressure , heart rate ( HR ) and pulse rate ( PR ) , state entropy ( SE ) and response entropy ( RE ) , and surgical pleth index ( SPI ) . New parameters complementing the above and characterizing the ANS state ( ANSS ) and responses are pulse-to-pulse interval ( PPI ) , pulse plethysmographic amplitude ( PPGA ) , ANSS , and an index based on maximal ANSS for the subject ( ANSSI ) . Serial data were stored as 10 s averages into a laptop computer . RESULTS Anaesthesia induction was associated with an increase in finger temperature to > 30 degrees C within 10 min , whereas PPGA increased to their maximum levels within 5 min . Laryngoscopy and intubation were associated with transient autonomic responses in most patients . All autonomic signs indicated statistically significant sympathetic activation during saline-infiltrated tonsillectomies when compared with lidocaine-infiltrated sides ( P<0001 ) . Hypnotic measures ( SE and RE ) and finger temperatures did not differ between the sides . CONCLUSIONS HR , PPI , PPGA , ANSS , ANSSI , SPI , and RE-SE detect autonomic responses to nociceptive stimuli and differentiate between tonsillectomies on locally anaesthetized tonsils from controls Being highly unstable , the critically ill polytrauma patient represents a challenge for the anaesthesia team . The aim of this study was to compare the Entropy and Surgical Pleth Index (SPI)—guided general anaesthesia with st and ard haemodynamic monitoring methods used in the critically ill polytrauma patients and to evaluate the incidence of hemodynamic events , as well as the opioid and vasopressor dem and . 72 patients were included in this prospect i ve observational study , divided in two groups , the ESPI Group ( N = 37 , patients that benefited from Entropy and SPI monitoring ) and the STDR Group ( N = 35 patients that benefited from st and ard hemodynamic monitoring ) . In the ESPI Group general anaesthesia was modulated in order to maintain the Entropy levels between 40 and 60 . Analgesia control was achieved by maintaining the SPI levels between 20 and 50 . In the STDR Group hypnosis and analgesia were maintained using the st and ard criteria based on hemodynamic changes . Clinical Trials.gov identifier NCT03095430 . The incidence of hypotension episodes was significantly lower in the ESPI Group ( N = 3 ) , compared to the STDR Group ( N = 71 ) ( p < 0.05 ) . Moreover , the Fentanyl dem and was significantly lower in the ESPI Group ( p < 0.0001 , difference between means 5.000 ± 0.038 , 95 % confidence interval 4.9250–5.0750 ) , as well as vasopressor medication dem and ( p < 0.0001 , difference between means 0.960 ± 0.063 , 95 % confidence interval 0.8.334–1.0866 ) . The implementation of multimodal monitoring in the critically ill polytrauma patient brings substantial benefits both to the intraoperative clinical status and to the clinical outcome of these patients by reducing the incidence of anesthesia-related complications Background : The effectiveness of surgical pleth index ( SPI ) for managing nociception-antinociception balance during general anesthesia with vasodilators , including nicardipine has not been demonstrated . We aim ed to compare the time course during surgery in SPI values in patients receiving nicardipine or remifentanil infusion during thyroidectomy . Methods : Forty patients undergoing thyroidectomy were r and omly assigned to receive nicardipine ( group N ; n = 19 ) or remifentanil ( group R ; n = 21 ) along with induction ( propofol , fentanyl , and rocuronium ) and maintenance ( 50 % desflurane/nitrous oxide in oxygen ) anesthesia ( goal bispectral index [ BIS ] ∼50 ) . The infusion of nicardipine or remifentanil was started before the 1st incision and adjusted to keep mean blood pressure ( MBP ) within ±20 % of the preoperative value . SPI , BIS , end-tidal desflurane concentration ( EtDes ) , MBP , and heart rate were recorded at 2.5 minute intervals from the 1st incision to the end of surgery . Extubation and recovery times , pain score/rescue ketorolac consumption , and adverse events in postanesthesia care unit ( PACU ) were recorded . Results : The trend of SPI during surgery was comparable between the 2 groups ( P = 0.804 ) , although the heart rates in group N were significantly higher than those in group R ( P = 0.040 ) . The patient characteristics , trends of BIS , EtDes , and MBP during surgery , extubation and recovery times , and incidence of nausea/vomiting were comparable between the groups . Group N had significantly lower pain scores and rescue ketorolac consumption at PACU . Conclusion : SPI was comparable between patients receiving nicardipine or remifentanil infusion during thyroidectomy under general anesthesia , which suggests that the administration of nicardipine may confound the interpretation of SPI values during general anesthesia . Clinical trial registration : This trial was registered in the UMIN clinical trials registry ( unique trial number : UMIN000019058 ; registration number : R000022028 ; principal investigator 's name : Young Ju Won ; date of registration : September 17 , 2015 ) BACKGROUND Monitoring of analgesia remains a challenge during general anaesthesia . The surgical stress index ( SSI ) is derived from the photoplethysmographic waveform amplitude and the heart beat-to-beat interval . We evaluated the ability of SSI to measure surgical stress in patients undergoing gynaecological laparoscopy . Our hypothesis was that while keeping State Entropy ( SE ) at a predetermined level , SSI would be higher in patients receiving a beta-blocking agent ( esmolol ) than in those receiving an opioid ( remifentanil ) during laparoscopy . METHODS Thirty women undergoing gynaecological laparoscopy were assigned r and omly to receive esmolol ( n = 15 ) or remifentanil ( n = 15 ) . Anaesthesia was induced with propofol and fentanyl and maintained with desflurane and nitrous oxide 50 % in oxygen to keep SE at 50(5 ) . The infusion of esmolol or remifentanil was started before laparoscopy and adjusted to keep the systolic blood pressure at -20 to + 10 % from the preoperative value . RESULTS During the fentanyl phase , before surgery , both groups behaved similarly , with an increase in SSI after intubation . In the patients receiving esmolol , the SSI reacted to the initial incision ( P < 0.05 ) , and remained high after trocar insertion ( P < 0.05 ) . In patients receiving remifentanil , it did not react to the initial incision , but increased after trocar insertion ( P < 0.05 ) , and it remained lower both after incision ( P < 0.05 ) and after trocar insertion ( P < 0.05 ) . CONCLUSION SSI was higher in patients receiving esmolol . The index seems to reflect the level of surgical stress and may help guide the use of opioids during general anaesthesia Background : The surgical pleth index ( SPI ) is proposed for titration of analgesic drugs during general anesthesia . Several reports have investigated the effect of SPI on the consumption of opioids including remifentanil , fentanyl , and sufentanil during anesthesia , but there are no reports about oxycodone . We aim ed to investigate intravenous oxycodone consumption between SPI-guided analgesia and conventional analgesia practice s during sevoflurane anesthesia in patients undergoing thyroidectomy . Methods : Forty-five patients undergoing elective thyroidectomy were r and omly assigned to an SPI group ( SPI-guided analgesia group , n = 23 ) or a control group ( conventional analgesia group , n = 22 ) . Anesthesia was maintained with sevoflurane to achieve bispectral index values between 40 and 60 . In the SPI group , oxycodone 1 mg was administered intravenously at SPI values over 50 ; in the control group , oxycodone 1 mg was administered intravenously at the occurrence of tachycardia or hypertension event . Intraoperative oxycodone consumption and extubation time were recorded . The number of hemodynamic and somatic movement events was recorded , as were postoperative pain and recovery scores . Results : Patients ’ characteristics were comparable between the groups . Intraoperative oxycodone consumption in the SPI group was significantly lower than the control group ( 3.5 ± 2.4 vs 5.1 ± 2.4 mg ; P = 0.012 ) . Extubation time was significantly shorter in the SPI group ( 10.6 ± 3.5 vs 13.4 ± 4.6 min ; P = 0.026 ) . Hemodynamic and somatic movement events during anesthesia were comparable between the groups , as were numeric rating scales for pain and modified Aldrete scores at postanesthesia care unit . Conclusions : SPI-guided analgesia reduces intravenous oxycodone consumption and extubation time compared with conventional analgesia based on clinical parameters during sevoflurane anesthesia in patients undergoing thyroidectomy BACKGROUND The surgical pleth index ( SPI ) is an index based on changes in plethysmographic characteristics that correlate with the balance between the sympathetic and parasympathetic nervous system . It has been proposed as a measure of the balance between nociception and anti-nociception . The goal of this study was to test whether it could be used to titrate remifentanil in day-case anaesthesia . METHODS A total of 170 out patients were given total i.v . anaesthesia with propofol and remifentanil . The patients were r and omized to have the remifentanil dose either adjusted according to the SPI ( SPI group ) or to clinical parameters ( control group ) . The propofol dose was adjusted according to entropy in both groups . The consumption of anaesthetic drugs , recovery times , and complications were compared . RESULTS The mean [ st and ard deviation ( SD ) ] remifentanil and propofol infusion rates in the SPI and control groups were 0.06 ( 0.04 ) vs 0.08 ( 0.05 ) µg kg(-1 ) min(-1 ) and 6.0 ( 2.1 ) vs 7.5 ( 2.2 ) mg kg(-1 ) h(-1 ) , respectively ( both P<0.05 ) . The mean ( SD ) times to eye opening were -0.08 ( 4.4 ) and 3.5 ( 4.3 ) min and to extubation were 1.2 ( 4.4 ) and 4.4 ( 4.5 ) min in the SPI and control groups , respectively ( both P<0.05 ) . There was no difference between the groups with regard to satisfaction with the anaesthetic or intensity of postoperative pain . No patient reported intraoperative awareness . CONCLUSIONS Adjusting the remifentanil dosage according to the SPI in outpatient anaesthesia reduced the consumption of both remifentanil and propofol and result ed in faster recovery BACKGROUND Evaluation of analgesia and antinociception during anaesthesia is still a challenging issue and routinely based on indirect and non-specific signs such as movement , tachycardia , or lacrimation . Recently , the surgical pleth index ( SPI ) derived by finger plethysmography was introduced to detect nociceptive stimulation during anaesthesia . While SPI guidance reduced the number of unwanted events during total i.v . anaesthesia ( TIVA ) , the impact of SPI during volatile-based anaesthesia with intermittent opioid administration has not yet been eluci date d. METHODS Ninety-four patients were r and omized into either SPI-guided analgesia or st and ard practice ( Control ) . In both groups , anaesthesia was maintained with sevoflurane to keep bispectral index values between 40 and 60 . In the SPI group , patients received a sufentanil bolus ( 10 μg ) whenever SPI value increased above 50 , whereas in the control group , sufentanil was administered according to st and ard clinical practice . The number of unwanted somatic events , haemodynamics , sufentanil consumption , and recovery times were recorded . RESULTS The incidence of intraoperative unwanted somatic events was comparable between the groups ( P=0.89 ) . No significant differences with respect to hypotensive or hypertensive events were found . The mean ( 95 % confidence interval ) sufentanil consumption was non-significantly ( P=0.07 ) reduced in the SPI group , 0.64 ( 0.57 - 0.71 ) vs 0.78 ( 0.64 - 0.91 ) µg min(-1 ) . Recovery times were comparable between the groups . CONCLUSIONS Sufentanil administration guided by SPI during sevoflurane anaesthesia is clinical ly feasible . In contrast to TIVA , it did not improve anaesthesia conduct with respect to unwanted somatic events , haemodynamic stability , sufentanil consumption , emergence time , or post-anaesthesia care unit care . Therefore , we conclude that anaesthesia regimen has an impact on beneficial effects by SPI guidance . Clinical trial registration NCT01525537 . ( Registered at Clinical trials.gov . ) BACKGROUND The Surgical Pleth Index ( SPI ) is proposed as a means to assess the balance between noxious stimulation and the anti-nociceptive effects of anaesthesia . In this study , we compared SPI , mean arterial pressure ( MAP ) , and heart rate ( HR ) as a means of assessing this balance . METHODS We studied a st and ard stimulus [ head-holder insertion ( HHI ) ] and varying remifentanil concentrations ( CeREMI ) in a group of patients undergoing neurosurgery . Patients receiving target-controlled infusions were r and omly assigned to one of the three CeREMI ( 2 , 4 , or 6 ng m⁻¹ ) , whereas propofol target was fixed at 3 µg ml⁻¹. Steady state for both targets was achieved before HHI . Intravascular volume status ( IVS ) was evaluated using respiratory variations in arterial pressure . Prediction probability ( Pk ) and ordinal regression were used to assess SPI , MAP , and HR performance at indicating CeREMI , and the influence of IVS and chronic treatment for high arterial pressure , as possible confounding factors . RESULTS The maximum SPI , MAP , or HR observed after HHI correctly indicated CeREMI in one of the two patients [ accurate prediction rate (APR)=0.5 ] . When IVS and chronic treatment for high arterial pressure were taken into account , the APR was 0.6 for each individual variable and 0.8 when all of them predicted the same CeREMI . That increase in APR paralleled an increase in Pk from 0.63 to 0.89 . CONCLUSIONS SPI , HR , and MAP are of comparable value at gauging noxious stimulation-CeREMI balance . Their interpretation is improved by taking account of IVS , treatment for chronic high arterial pressure , and concordance between their predictions BACKGROUND The surgical pleth index ( SPI ) is a measurement of intraoperative nociception . Evidence of its usability in children is limited . Given that the autonomic nervous system is still developing during the first years of life , the performance of the SPI on small children can not be concluded from studies carried out in older age groups . METHODS Thirty children aged < 2 yr , planned for elective open inguinal hernia repair or open correction of undescended testicle , were recruited . The children were r and omized into two groups ; the saline group received ultrasound-guided saline injection in the ilioinguinal and iliohypogastric nerve region before surgery and ropivacaine after surgery , whereas the block group received the injections in the opposite order . The SPI was recorded blinded and was analysed at the time points of intubation , incision , and when signs of inadequate anti-nociception were observed . RESULTS There was a significant increase in the SPI after intubation ( P=0.019 ) and after incision in the saline group ( P=0.048 ) , but not at the time of surgical incision in the block group ( P=0.177 ) . An increase in the SPI was also seen at times of clinical ly apparent inadequate anti-nociception ( P=0.008 ) . The between-patient variability of the SPI was large . CONCLUSIONS The SPI is reactive in small children after intubation and after surgical stimuli , but the reactivity of the SPI is rather small , and there is marked inter-individual variability in reactions . The reactivity is blunted by the use of ilioinguinal and iliohypogastric nerve block . CLINICAL TRIAL REGISTRATION NCT02045810 BACKGROUND Pupillometry has shown promising results for assessing nociception in anesthetized patients . However , its benefits in clinical practice are not demonstrated . The aim of this prospect i ve r and omized study was to evaluate the impact of intraoperative pupillometry monitoring on perioperative opioid consumption in major gynecologic surgery . METHODS After receiving ethics committee approval and written consent of patients , American Society of Anesthesiologists status I to II women undergoing gynecologic surgery were included in this single-blinded , prospect i ve , parallel-arm r and omized study . General anesthesia was st and ardized with propofol-remifentanil target-controlled infusion . Patients were r and omly assigned into two groups . In the pupillometry group , remifentanil administration was guided by pupillary diameter changes . In the st and ard group , remifentanil administration was left to the discretion of the anesthesiologist . The primary outcome was intraoperative remifentanil consumption . RESULTS Fifty-five patients were analyzed . Remifentanil consumption was markedly decreased in the pupillometry group ( 3.8 [ 3.4 to 4.8 µg · kg · h ] vs. 7.9 µg · kg · h [ 6.5 to 9.0 µg · kg · h ] in the st and ard group ; difference = 4.2 µg · kg · h [ 95 % CI , 3.0 to 5.3 µg · kg · h ] ; P < 0.001 ) . Cumulative 0- to 12-h morphine consumption was reduced in the pupillometry group ( two-way repeated measures ANOVA 0.3 ± 0.1 vs. 0.4 ± 0.2 mg/kg ; P = 0.048 ) . A telephone survey 3 months after surgery revealed that 15 of 29 patients in the st and ard group still experienced procedure-related pain versus 3 of 23 in the pupillometry group ( chi-square P = 0.037 ) . No adverse events associated with pupillometry were observed during the study . CONCLUSIONS The use of pupillometry to guide intraoperative analgesia reduced intraoperative remifentanil consumption and postoperative morphine requirements . The possible consequences of decreasing intraoperative remifentanil in terms of chronic pain require further investigation Background : To compare surgical pleth index (SPI)-guided analgesia with conventional analgesia by evaluating intraoperative analgesic requirements , postoperative pain , and emergence agitation in children . Methods : This study was design ed as a parallel , two-arm , double-blind , r and omized controlled trial . Forty-five children undergoing elective adenotonsillectomy were r and omly allocated to SPI-guided group ( SPI-guided analgesia group , n = 21 ) or control group ( conventional analgesia group , n = 24 ) . Anesthesia was maintained with sevoflurane 2 to 3 vol% in 50 % nitrous oxide and oxygen to achieve state entropy between 40 and 60 . Intraoperative fentanyl 0.5 & mgr;g/kg was administered for the first event persisting 3 min and subsequent events persisting 5 min . An event was defined as an SPI over 50 ( SPI-guided group ) or a blood pressure or heart rate 20 % above the baseline ( control group ) . The primary outcome was intraoperative fentanyl requirement . Secondary outcomes included intraoperative sevoflurane consumption , postoperative emergence agitation and pain score , and postoperative rescue analgesic requirements . Results : Intraoperative fentanyl requirement was lower in SPI-guided group than in control group ( 0.43 ± 0.53 vs. 1.73 ± 0.59 & mgr;g/kg ; P < 0.001 ) . Intraoperative sevoflurane consumption was similar . The proportion of patients with high emergence agitation scores ( 4 to 5 ) was greater in SPI-guided group ( 61.9 vs. 25.0 % ; P = 0.01 ) . The postoperative pain score and rescue fentanyl consumption were higher in SPI-guided group ( 7 [ 4.5 ; 9 ] vs. 3 [ 2 ; 6.75 ] ; P = 0.002 ; 0.50 ± 0.34 vs. 0.29 ± 0.30 & mgr;g/kg ; P = 0.04 ) . Conclusions : As currently constructed , SPI does not appear to be valid in children . This may be due to both differences in blood vessel distensibility and baseline increased heart rates in children versus adults |
12,902 | 25,938,479 | There is no current evidence to support the use of homocysteine lowering therapy for cardiovascular disease prevention in kidney transplant recipients | BACKGROUND Elevated homocysteine levels have been shown to be an independent risk factor for cardiovascular disease .
However studies of homocysteine lowering in general and end-stage kidney disease ( ESKD ) population s have not demonstrated a reduction in cardiovascular event rates .
Kidney transplant recipients have high homocysteine levels , high cardiovascular event rates and , unlike the ESKD population , may achieve normalisation of homocysteine levels with homocysteine lowering therapies .
Thus may benefit from homocysteine lowering therapy .
OBJECTIVES To evaluate the effects of established homocysteine lowering therapy on cardiovascular mortality in patients with functioning kidney transplants . | The aim of this study was to assess the relationship between total plasma homocysteine ( tHC ) and several markers of endothelial function , coagulation , and pro-inflammatory status in renal transplant recipients . Our own previous study demonstrated the efficacy of folic acid ( FA ) and vitamin B(12 ) ( B(12 ) ) treatment to reduce tHC . Using 70 stable recipients , 56 of whom showed hyperhomocisteinemia ( HHC ) ( tHC > or = 14 micromol/L ) and a control group ( n = 14 , tHC < 14 micromol/L ) , we treated 29 patients in the HHC group ( 10 mg FA and 500 mg B(12 ) daily ) and determined their endothelial function , inflammatory activity , and coagulation status . We assessed plasma levels of von Willebr and Factor and fibrinogen as the prothrombotic profile and C-reactive protein and plasma albumin as inflammation markers . We performed Doppler sonography of the brachial artery to assess endothelial function . The mean value of plasma tHC of 19.05 + /- 3.70 micromol/L before treatment decreased to 13.45 + /- 3.25 micromol/L after 3 months of treatment ( P < .001 ) . The vWF was significantly correlated with tHC ( P < .05 ) and was higher in the HHC patients ( P < .05 ) . The fibrinogen mean level was also significantly higher in HHC patients ( P < .05 ) . The C-reactive protein level was significantly higher and the albumin level was lower among patients with HHC . The endothelium-dependent dilation ( EDD ) correlated with baseline tHC ( P < .05 ) . In preliminary data we observed that homocysteine-lowering therapy may provide cardiovascular protection by enhancing endothelial function , limiting oxidative stress , and reducing procoagulation status BACKGROUND The hyperhomocysteinemia regularly found in hemodialysis patients is largely refractory to combined oral B-vitamin supplementation featuring supraphysiological doses of folic acid . We evaluated whether a high-dose L-5-methyltetrahydrofolate-based regimen provided improved total homocysteine (tHcy)-lowering efficacy in chronic hemodialysis patients . METHODS AND RESULTS We block-r and omized 50 chronic , stable hemodialysis patients on the basis of their screening predialysis tHcy levels , sex , and dialysis center into 2 groups of 25 subjects treated for 12 weeks with oral folic acid at 15 mg/d ( FA group ) or an equimolar amount ( 17 mg/d ) of oral L-5-methyltetrahydrofolate ( MTHF group ) . All 50 subjects also received 50 mg/d of oral vitamin B(6 ) and 1.0 mg/d of oral vitamin B(12 ) . The mean percent reductions ( + /-95 % CIs ) in predialysis tHcy were not significantly different : MTHF , 17.0 % ( 12.0 % to 22.0 % ) ; FA , 14.8 % ( 9.6 % to 20.1 % ) ; P=0.444 by matched ANCOVA adjusted for pretreatment tHcy . Final on-treatment values ( mean with 95 % CI ) were MTHF , 20.0 micromol/L ( 18.8 to 21.2 micromol/L ) ; FA , 19.5 micromol/L ( 18.3 to 20.7 micromol/L ) . Moreover , neither treatment result ed in " normalization " of tHcy levels ( ie , final on-treatment values < 12 micromol/L ) among a significantly different or clinical ly meaningful number of patients : MTHF , 2 of 25 ( 8 % ) ; FA , 0 of 25 ( 0 % ) ; Fisher 's exact test of between-groups difference , P=0.490 . CONCLUSIONS Relative to high-dose folic acid , high-dose oral L-5-methyltetrahydrofolate-based supplementation does not afford improved tHcy-lowering efficacy in hemodialysis patients . The preponderance of hemodialysis patients ( ie , > 90 % ) exhibit mild hyperhomocysteinemia refractory to treatment with either regimen . This treatment refractoriness is not related to defects in folate absorption or circulating plasma and tissue distribution The mild fasting hyperhomocysteinemia commonly observed in chronic ( ie , > /=6 months posttransplantation ) renal transplant recipients ( RTRs ) can be effectively treated with combined B-vitamin supplementation featuring supraphysiological doses of folic acid . There are no controlled data evaluating the comparative efficacy of supraphysiological versus st and ard multivitamin dose folic acid supplementation in reducing fasting total homocysteine ( tHcy ) levels among RTRs . We block-r and omized 60 chronic , stable RTRs on the basis of their screening fasting tHcy level to 3 groups of 20 subjects treated for 12 weeks with folic acid at either 2.4 ( group 1 ) , 0.4 ( ie , st and ard multivitamin dose ) ( group 2 ) , or 0.0 ( group 3 ) mg/d . All 60 study participants also received 50 mg/d vitamin B(6 ) and 0.4 mg/d vitamin B(12 ) . The mean percent reductions ( + /-SEM ) in fasting tHcy were as follows : group 1 , 32.3+/-2.4 % ; group 2 , 23.4+/-2.3 % ; and group 3 , 19.1+/-2.3 % . ANCOVA accounting for the pretreatment matching and adjusted for pretreatment levels of fasting tHcy , folate , and albumin ; change in creatinine during the study ; and cyclosporine A use revealed significant overall group differences ( P=0.005 ) and significant differences between groups 1 and 2 ( P=0 . 038 ) and groups 1 and 3 ( P=0.001 ) , but not between groups 2 and 3 ( P=0.153 ) . Moreover , a chi(2 ) analysis of participants with pretreatment tHcy levels > /=15 micromol/L ( n=29 ) indicated that a significantly greater proportion of those in group 1 achieved posttreatment levels < 12 micromol/L : group 1 , 5 of 10 ( 50 % ) ; group 2 , 1 of 11 ( 9 % ) ; and group 3 , 0 of 8 ( 0 % ) ( P=0.016 ; test of trend P=0 . 007 ) . We conclude that a supraphysiological dose of folic acid is superior to st and ard multivitamin dosing for the reduction of fasting tHcy levels in chronic RTRs BACKGROUND Mild hyperhomocysteinemia is common among maintenance hemodialysis ( HD ) patients and renal transplant recipients ( RTR ) and may contribute to the excess incidence of arteriosclerotic outcomes experienced by both patient groups . Relative to their RTR counterparts , the hyperhomocysteinemia of HD patients seems to be considerably more refractory to treatment with high-dose folic acid (FA)-based B-vitamin supplementation regimens , although controlled comparison data are lacking . METHODS We compared the relative responsiveness of ( n=10 ) RTR and ( n=39 ) HD patients with equivalent baseline total homocysteine ( tHcy ) levels ( i.e. , RTR range=14.2 - 23.6 micromol/L ; HD range=14.4 - 24.9 micromol/L ) to 12 weeks of tHcy-lowering treatment . The RTR received 2.4 mg/day of FA , 50.0 mg/day of vitamin B6 , and 0.4 mg/day of vitamin B12 , while the HD patients received 15 mg/day of FA or an equimolar amount ( 17 mg/day ) of the reduced folate , L-5-methyltetrahydrofolate , in addition to 50.0 mg/day of vitamin B6 , and 1.0 mg/day of vitamin B12 . RESULTS The mean percent ( % ) reductions ( + /-95 % confidence interval ) in tHcy were : RTR=28.1 % ( 16.2 - 40.0 % ) ; HD=12.1 % ( 6.6 - 17.7 % ) , P=0.027 for comparison of between-groups differences by analysis of covariance adjusted for baseline tHcy levels . Moreover , ( 50.0 % ) of 10 of the RTR versus only ( 5.1 % ) of 39 of the HD patients had final on-treatment tHcy levels < 12 micromol/L ; P=0.002 for comparison of between-groups differences by Fisher 's exact test . CONCLUSION Relative to RTR with comparable baseline tHcy levels , the mild hyperhomocysteinemia of maintenance HD patients is much more refractory to tHcy-lowering B-vitamin treatment regimens featuring supraphysiological amounts of FA or the reduced folate , L-5-methyltetrahydrofolate . Accordingly , RTR are a preferable target population for controlled clinical trials testing the hypothesis that tHcy-lowering B-vitamin intervention may reduce arteriosclerotic cardiovascular disease event rates in patients with chronic renal disease BACKGROUND Homocysteine is a risk factor for cardiovascular disease . We evaluated the efficacy of homocysteine-lowering treatment with B vitamins for secondary prevention in patients who had had an acute myocardial infa rct ion . METHODS The trial included 3749 men and women who had had an acute myocardial infa rct ion within seven days before r and omization . Patients were r and omly assigned , in a two-by-two factorial design , to receive one of the following four daily treatments : 0.8 mg of folic acid , 0.4 mg of vitamin B12 , and 40 mg of vitamin B6 ; 0.8 mg of folic acid and 0.4 mg of vitamin B12 ; 40 mg of vitamin B6 ; or placebo . The primary end point during a median follow-up of 40 months was a composite of recurrent myocardial infa rct ion , stroke , and sudden death attributed to coronary artery disease . RESULTS The mean total homocysteine level was lowered by 27 percent among patients given folic acid plus vitamin B12 , but such treatment had no significant effect on the primary end point ( risk ratio , 1.08 ; 95 percent confidence interval , 0.93 to 1.25 ; P=0.31 ) . Also , treatment with vitamin B6 was not associated with any significant benefit with regard to the primary end point ( relative risk of the primary end point , 1.14 ; 95 percent confidence interval , 0.98 to 1.32 ; P=0.09 ) . In the group given folic acid , vitamin B12 , and vitamin B6 , there was a trend toward an increased risk ( relative risk , 1.22 ; 95 percent confidence interval , 1.00 to 1.50 ; P=0.05 ) . CONCLUSIONS Treatment with B vitamins did not lower the risk of recurrent cardiovascular disease after acute myocardial infa rct ion . A harmful effect from combined B vitamin treatment was suggested . Such treatment should therefore not be recommended . ( Clinical Trials.gov number , NCT00266487 . ) OBJECTIVE To study the effect of vitamin B on treatment of hyperhomocysteinemia and endothelial dysfunction in renal-transplant recipients . METHODS Thirty-six stable hyperhomocysteinemic renal-transplant recipients were r and omly assigned to vitamin treatment ( group A , n = 18 , folic acid 5 mg/d , vitamin B(6 ) 50 mg/d , B(12 ) 1000 microg/d ) or controlled group ( group B , n = 18 ) for 6 months . All subjects underwent assessment of levels for creatinine , creatinine clearance , average pressure , total cholesterol , triglyceride and fasting homocysteine . Endothelial function was evaluated using high-resolution vascular ultrasound . RESULTS The levels of homocysteine markedly decreased in group A [ ( 13 + /- 4 ) micromol/L vs ( 20 + /- 5 ) micromol/L , t = 5.3 , P < 0.01 ] after treatment , whereas no significant changes were observed in group B. In group A , endothelium dependent [ ( 12 + /- 5)% vs ( 9 + /- 5)% , t = 2.9 , P < 0.01 ] and independent [ ( 18 + /- 4)% vs ( 12 + /- 5)% , t = 3.4 , P < 0.01 ] vasodilatation responses significantly increased after treatment , no significant changes were observed in group B. Endothelium dependent [ ( 9 + /- 6)% , t = 2.8 , P < 0.01 ] and independent [ ( 12 + /- 5)% , t = 3.5 , P < 0.01 ] vasodilatation responses of group A were significantly lower than that of group B after treatment . CONCLUSIONS Vitamin B supplementation can reduce the levels of homocysteine and improve the endothelial function in hyperhomocysteinemic renal-transplant recipients Renal transplant recipients have disproportionately high rates of arteriosclerotic outcomes , and recent studies provided controlled evidence that clinical ly stable renal transplant recipients have an excess prevalence of hyperhomocysteinemia . Few studies suggest that hyperhomocysteinemia may be a cardiovascular risk factor in renal transplant recipients . In the study presented here , the association between atherosclerotic events and homocysteine concentrations was examined in 207 stable renal transplant recipients . The role of hyperhomocysteinemia was analyzed with respect to other known cardiovascular risk factors . The mean follow-up was 21.2 + /- 1.9 mo ( range , 14 to 26 ) . Mean total homocysteine ( tHcy ) was 21.1 + /-9.5 micromol/L and median concentration was 19 micromol/L. Seventy percent of patients ( n = 153 ) were hyperhomocysteinemic ( values > 15 micromol/L ) . tHcy correlated negatively with folate concentration ( r = -0.3 ; P < 0.01 ) . tHcy was closely related to creatinine concentration ( r = 0.54 ; P < 0.001 ) . Cardiovascular disease events ( CVE ) including death were observed in 30 patients ( 14.5 % ; 7.34 events per 1000 person-months of follow-up ) . Fasting tHcy values were higher in patients who experienced CVE ( 31.5 + /- 10.3 versus 17.8 + /- 7.5 ; P < 0.001 ) . Cox regression analysis showed that tHcy was a risk factor for cardiovascular complications ( relative risk [ RR ] 1.06 ; 95 % confidence interval ( 95 % CI ) , 1.04 to 1.09 ; P < 0.0001 ) . This corresponds to an increase in RR for CVE of 6 % per micromol/L increase in tHcy concentration . Age ( RR 1.55 ; 95 % CI , 1.09 to 2.19 ; P < 0.01 ) and creatinine concentration ( RR 1.34 ; 95 % CI , 1.08 to 1.66 ; P < 0.01 ) were also independent predictors for CVE . This study demonstrates that elevated fasting tHcy is an independent risk factor for the development of CVE in chronic stable renal transplant recipients . R and omized , placebo-controlled homocysteine studies of the effect of tHcy lowering on CVE rates are urgently required in this patient population Background — Kidney transplant recipients , like other patients with chronic kidney disease , experience excess risk of cardiovascular disease and elevated total homocysteine concentrations . Observational studies of patients with chronic kidney disease suggest increased homocysteine is a risk factor for cardiovascular disease . The impact of lowering total homocysteine levels in kidney transplant recipients is unknown . Methods and Results — In a double-blind controlled trial , we r and omized 4110 stable kidney transplant recipients to a multivitamin that included either a high dose ( n=2056 ) or low dose ( n=2054 ) of folic acid , vitamin B6 , and vitamin B12 to determine whether decreasing total homocysteine concentrations reduced the rate of the primary composite arteriosclerotic cardiovascular disease outcome ( myocardial infa rct ion , stroke , cardiovascular disease death , resuscitated sudden death , coronary artery or renal artery revascularization , lower-extremity arterial disease , carotid endarterectomy or angioplasty , or abdominal aortic aneurysm repair ) . Mean follow-up was 4.0 years . Treatment with the high-dose multivitamin reduced homocysteine but did not reduce the rates of the primary outcome ( n=547 total events ; hazards ratio [ 95 confidence interval]=0.99 [ 0.84 to 1.17 ] ) , secondary outcomes of all-cause mortality ( n=431 deaths ; 1.04 [ 0.86 to 1.26 ] ) , or dialysis-dependent kidney failure ( n=343 events ; 1.15 [ 0.93 to 1.43 ] ) compared to the low-dose multivitamin . Conclusions — Treatment with a high-dose folic acid , B6 , and B12 multivitamin in kidney transplant recipients did not reduce a composite cardiovascular disease outcome , all-cause mortality , or dialysis-dependent kidney failure despite significant reduction in homocysteine level . Clinical Trial Registration — http://www . clinical trials.gov . Unique identifier : NCT00064753 BACKGROUND Patients with chronic kidney disease , including kidney transplant recipients , are at high risk for cardiovascular disease ( CVD ) . In addition to the constellation of traditional CVD risk factors in chronic kidney disease , elevated total homocysteine ( tHcy ) is notably more prevalent among the general population . The Folic Acid for Vascular Outcome Reduction In Transplantation ( FAVORIT ) trial is design ed to evaluate whether lowering tHcy using vitamin supplementation reduces CVD events in renal transplant recipients . METHODS FAVORIT is a multicenter double-blind r and omized controlled clinical trial . Participants are clinical ly stable renal transplant recipients who are 6 months or longer posttransplant with elevated tHcy . Patients are r and omized to a multivitamin that includes either a high-dose or low-dose of folic acid ( 5 or 0 mg ) , vitamin B6 ( 50 or 1.4 mg ) , and vitamin B12 ( 1000 or 2 microg ) . The primary end point is a composite of incident or recurrent CVD outcomes , that is , coronary heart , cerebrovascular , or abdominal aortic/lower extremity arterial events . A sample size of 4000 is estimated to provide 87 % power to detect a 20 % treatment effect . Recruitment is expected to continue until July 2006 , with follow-up through June 2010 . RESULTS From August 2002 through December 2004 , 2234 of the target 4000 patients were enrolled . In accordance with trial design , mean ( SD ) screening tHcy was elevated ( 17.4 + /- 6.2 micromol/L ) , and mean ( SD ) estimated creatinine clearance was consistent with stable renal function ( 58.0 + /- 18.6 mL/min ) . Evaluating baseline results to date , 42 % of the r and omized participants had a history of diabetes mellitus , and 21 % had prevalent CVD . CONCLUSIONS The FAVORIT trial is design ed with sufficient power and follow-up time to detect a clinical ly relevant change in CVD risk between renal transplant recipients receiving a high or low tHcy-lowering folic acid multivitamin . Preliminary screening and baseline data support the trial 's objectives BACKGROUND Renal transplant recipients are at increased risk of premature cardiovascular disease . Although statins reduce cardiovascular risk in the general population , their efficacy and safety in renal transplant recipients have not been established . We investigated the effects of fluvastatin on cardiac and renal endpoints in this population . METHODS We did a multicentre , r and omised , double-blind , placebo-controlled trial in 2102 renal transplant recipients with total cholesterol 4.0 - 9.0 mmol/L. We r and omly assigned patients fluvastatin ( n=1050 ) or placebo ( n=1052 ) and follow up was for 5 - 6 years . The primary endpoint was the occurrence of a major adverse cardiac event , defined as cardiac death , non-fatal myocardial infa rct ion ( MI ) , or coronary intervention procedure . Secondary endpoints were individual cardiac events , combined cardiac death or non-fatal MI , cerebrovascular events , non-cardiovascular death , all-cause mortality , and graft loss or doubling of serum creatinine . Analysis was by intention to treat . FINDINGS After a mean follow-up of 5.1 years , fluvastatin lowered LDL cholesterol concentrations by 32 % . Risk reduction with fluvastatin for the primary endpoint ( risk ratio 0.83 [ 95 % CI 0.64 - 1.06 ] , p=0.139 ) was not significant , although there were fewer cardiac deaths or non-fatal MI ( 70 vs 104 , 0.65 [ 0.48 - 0.88 ] p=0.005 ) in the fluvastatin group than in the placebo group . Coronary intervention procedures and other secondary endpoints did not differ significantly between groups . INTERPRETATION Although cardiac deaths and non-fatal MI seemed to be reduced , fluvastatin did not generally reduce rates of coronary intervention procedures or mortality . Overall effects of fluvastatin were similar to those of statins in other population Moderate hyperhomocysteinaemia has been shown to constitute an independent risk factor for cardiovascular disease ( CVD ) , a frequent cause of morbidity and mortality in renal transplant recipients ( RTR ) . In these patients few data regarding both total homocysteine levels and their influence on cardiovascular risk have been reported . We therefore studied serum homocysteine levels in deep-frozen sera from 42 kidney transplant recipients with a follow-up of 11 + /- 4.5 years ( mean + /- SD ) after transplantation . Eighteen patients had one or more ischaemic events ( CVD ( + ) ) and 24 patients had none ( CVD ( - ) ) . Serum sample s had been drawn 1 - 6 months prior to the first vascular event in CVD ( + ) patients and serum storage time was comparable in both CVD ( - ) and CVD ( + ) patients . Serum homocysteine levels were measured using a radioenzymatic method . Mean homocysteine level was significantly higher in 42 RTR males and females ( 15.5 + /- 6.3 , 13.5 + /- 5.5 microM respectively ) compared with 35 control subjects matched for age and sex ( 8.7 + /- 1.9 , 7.5 + /- 1.9 microM , P < 0.001 ) . The difference in serum homocysteine levels between CVD ( + ) and CVD ( - ) RTR nearly reached statistical significance in male patients ( 18.6 + /- 7.8 versus 13.1 + /- 3.4 microM , P < 0.06 ) but not in female patients ( P = NS ) . In the CVD ( + ) group 11/18 patients had homocysteine levels > 14 microM ( the upper limit in healthy controls ) versus 7/24 in the CVD ( - ) group ( P = 0.04 ) . In these patients we simultaneously measured in the same serum sample s , serum triglycerides , and total and HDL cholesterol , and calculated LDL cholesterol . By stepwise discriminant analysis and by logistic regression analysis in this relatively small patient population , only serum triglycerides and homocysteine were selected as risk factors associated with CVD . We conclude that significant hyperhomocysteinaemia is present in renal transplant recipients and represents a potential risk factor for cardiovascular disease in these patients BACKGROUND In observational studies , lower homocysteine levels are associated with lower rates of coronary heart disease and stroke . Folic acid and vitamins B6 and B12 lower homocysteine levels . We assessed whether supplementation reduced the risk of major cardiovascular events in patients with vascular disease . METHODS We r and omly assigned 5522 patients 55 years of age or older who had vascular disease or diabetes to daily treatment either with the combination of 2.5 mg of folic acid , 50 mg of vitamin B6 , and 1 mg of vitamin B12 or with placebo for an average of five years . The primary outcome was a composite of death from cardiovascular causes , myocardial infa rct ion , and stroke . RESULTS Mean plasma homocysteine levels decreased by 2.4 micromol per liter ( 0.3 mg per liter ) in the active-treatment group and increased by 0.8 micromol per liter ( 0.1 mg per liter ) in the placebo group . Primary outcome events occurred in 519 patients ( 18.8 percent ) assigned to active therapy and 547 ( 19.8 percent ) assigned to placebo ( relative risk , 0.95 ; 95 percent confidence interval , 0.84 to 1.07 ; P=0.41 ) . As compared with placebo , active treatment did not significantly decrease the risk of death from cardiovascular causes ( relative risk , 0.96 ; 95 percent confidence interval , 0.81 to 1.13 ) , myocardial infa rct ion ( relative risk , 0.98 ; 95 percent confidence interval , 0.85 to 1.14 ) , or any of the secondary outcomes . Fewer patients assigned to active treatment than to placebo had a stroke ( relative risk , 0.75 ; 95 percent confidence interval , 0.59 to 0.97 ) . More patients in the active-treatment group were hospitalized for unstable angina ( relative risk , 1.24 ; 95 percent confidence interval , 1.04 to 1.49 ) . CONCLUSIONS Supplements combining folic acid and vitamins B6 and B12 did not reduce the risk of major cardiovascular events in patients with vascular disease . ( Clinical Trials.gov number , NCT00106886 ; Current Controlled Trials number , IS RCT N14017017 . ) CONTEXT Recent r and omized trials among patients with preexisting cardiovascular disease ( CVD ) have failed to support benefits of B-vitamin supplementation on cardiovascular risk . Observational data suggest benefits may be greater among women , yet women have been underrepresented in published r and omized trials . OBJECTIVE To test whether a combination of folic acid , vitamin B6 , and vitamin B12 lowers risk of CVD among high-risk women with and without CVD . DESIGN , SETTING , AND PARTICIPANTS Within an ongoing r and omized trial of antioxidant vitamins , 5442 women who were US health professionals aged 42 years or older , with either a history of CVD or 3 or more coronary risk factors , were enrolled in a r and omized , double-blind , placebo-controlled trial to receive a combination pill containing folic acid , vitamin B6 , and vitamin B12 or a matching placebo , and were treated for 7.3 years from April 1998 through July 2005 . INTERVENTION Daily intake of a combination pill of 2.5 mg of folic acid , 50 mg of vitamin B6 , and 1 mg of vitamin B12 . MAIN OUTCOME MEASURES A composite outcome of myocardial infa rct ion , stroke , coronary revascularization , or CVD mortality . RESULTS Compared with placebo , a total of 796 women experienced a confirmed CVD event ( 406 in the active group and 390 in the placebo group ) . Patients receiving active vitamin treatment had similar risk for the composite CVD primary end point ( 226.9/10,000 person-years vs 219.2/10,000 person-years for the active vs placebo group ; relative risk [ RR ] , 1.03 ; 95 % confidence interval [ CI ] , 0.90 - 1.19 ; P = .65 ) , as well as for the secondary outcomes including myocardial infa rct ion ( 34.5/10,000 person-years vs 39.5/10,000 person-years ; RR , 0.87 ; 95 % CI , 0.63 - 1.22 ; P = .42 ) , stroke ( 41.9/10,000 person-years vs 36.8/10,000 person-years ; RR , 1.14 ; 95 % CI , 0.82 - 1.57 ; P = .44 ) , and CVD mortality ( 50.3/10,000 person-years vs 49.6/10,000 person-years ; RR , 1.01 ; 95 % CI , 0.76 - 1.35 ; P = .93 ) . In a blood sub study , geometric mean plasma homocysteine level was decreased by 18.5 % ( 95 % CI , 12.5%-24.1 % ; P < .001 ) in the active group ( n = 150 ) over that observed in the placebo group ( n = 150 ) , for a difference of 2.27 micromol/L ( 95 % CI , 1.54 - 2.96 micromol/L ) . CONCLUSION After 7.3 years of treatment and follow-up , a combination pill of folic acid , vitamin B6 , and vitamin B12 did not reduce a combined end point of total cardiovascular events among high-risk women , despite significant homocysteine lowering . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000541 OBJECTIVES We investigated the effects of folic acid supplementation on plasma total homocysteine levels and carotid intima-media thickness after kidney transplant . MATERIAL S AND METHODS Sixty patients who had undergone a kidney transplant were studied in this double-blind , r and omized , placebo-controlled clinical trial . Those subjects were r and omized to receive either 5 mg/d of oral folic acid or an equivalent dosage of placebo . The main outcome variables were the plasma total homocysteine level and carotid intima-media thickness ( determined via B-mode sonography ) at baseline and 2 , 4 , and 6 months after kidney transplant . We used independent and paired sample t tests for data analysis . RESULTS The mean age of the patients was 40.9 -/+ 10 years , and 32 of those subjects ( 58.2 % ) were men . In the control group , the plasma total homocysteine levels were 19 micromol/L at baseline , 18.7 micromol/L after 2 months , 19.3 micromol/L after 4 months , and 20 micromol/L after 6 months ; and the carotid intima-media thickness measurements were 0.81 mm at baseline , 0.82 mm after 2 months , 0.84 mm after 4 months , and 0.85 mm after 6 months . In the folic acid group , the plasma total homocysteine levels were 18.5 micromol/L at baseline , 4.7 micromol/L after 2 months , 12.9 micromol/L after 4 months , and 10.9 micromol/L after 6 months ; and the carotid intima-media thickness measurements were 0.73 mm at baseline , 0.73 mm after 2 months , 0.72 mm after 4 months , and 0.71 mm after 6 months . CONCLUSIONS Folic acid supplementation reduces both the plasma total homocysteine level and carotid intima-media thickness shortly after kidney transplant BACKGROUND Hyperhomocysteinemia may be a modifiable risk factor for the prevention of arteriosclerotic outcomes in patients with chronic kidney disease ( CKD ) . Few clinical trials of homocysteine lowering have been conducted in persons with CKD before reaching end-stage renal disease . Kidney transplant recipients are considered individuals with CKD . OBJECTIVES To describe the baseline characteristics of renal transplant recipients enrolled in a clinical trial of homocysteine lowering with a st and ard multivitamin containing high doses of folic acid and vitamins B(6 ) and B(12 ) aim ed at reducing arteriosclerotic outcomes . Factors considered were level of kidney function , total homocysteine concentration , and prevalence of diabetes and previous cardiovascular disease ( CVD ) . STUDY DESIGN Cross-sectional survey within a r and omized controlled trial cohort . SETTING & PARTICIPANTS Participants were recruited from kidney transplant clinics in the United States , Canada , and Brazil . Eligible participants had increased levels of homocysteine ( > or = 12.0 micromol/L in men and > or = 11.0 micromol/L in women ) and kidney function measured by means of Cockroft-Gault estimated creatinine clearance of 30 mL/min or greater . RESULTS Of 4,110 r and omly assigned participants , 38.9 % had diabetes and 19.5 % had previous CVD . Mean total homocysteine concentration was 17.1 + /- 6.3 ( SD ) micromol/L , whereas mean creatinine clearance was 66.4 + /- 23.2 mL/min . Approximately 90 % of the trial cohort had an estimated glomerular filtration rate consistent with stages 2 to 3 CKD ( i.e. , 30 to 89 mL/min ) . LIMITATIONS Analysis is based on cross-sectional data from a r and omized controlled trial , self-report of comorbid illnesses , and level of kidney function was estimated . CONCLUSIONS A large population of stable renal transplant recipients who are at high risk of the development of CVD ( both de novo and recurrent ) has been recruited into the Folic Acid for Vascular Outcome Reduction in Transplantation Trial and are likely to experience a sufficient number of events to address the primary hypothesis of the trial Background . The reduction in renal transplant rejection rates achieved over the last 20 years have not translated into a commensurate improvement in long-term graft survival . Cyclosporine has been central to immunosuppressive regimens throughout this period but its effect on long-term transplant outcomes remains unclear . Methods . This r and omized controlled trial allocated first cadaveric renal transplant recipients in seven centers around Australia to three immunosuppressive regimens : azathioprine and prednisolone ( AP ) , long-term cyclosporine alone ( Cy ) , or cyclosporine initiation followed by withdrawal at 3 months and azathioprine and prednisolone replacement ( WDL ) . Results . Between 1983 and 1986 , 489 patients were r and omized with 98 % follow-up to a median of 20.6 years . Mean graft survival ( censoring deaths ) was superior in the WDL group ( 14.8 years ) when compared with both AP ( 12.4 years , P=0.01 log-rank test ) and Cy ( 12.5 years , P=0.01 log-rank test ) groups by intention-to-treat . Without death censoring , graft survival with WDL was superior to AP ( 9.5 years vs. 6.7 years , P=0.04 ) and of borderline superiority to Cy ( 9.5 years vs. 8.5 years , P=0.06 ) . Patient survival was not different between the three groups . Renal function was superior in AP ( at 1 , 10 , and 15 years posttransplant ) and WDL ( at 1 , 5 , 10 , 15 , and 20 years ) groups when compared with Cy . Conclusion . This study illustrates superior long-term renal transplant survival and preservation of renal function with a protocol using cyclosporine withdrawal . If long-term renal transplant outcomes are to improve , we should reconsider guidelines recommending universal maintenance use of cyclosporine Homocysteine is implicated to be an atherogenic amino acid and has been associated with increased risk of adverse cardiovascular outcomes . The prognostic significance of plasma total homocysteine ( tHcy ) levels for mortality and allograft loss in kidney transplant recipients has not been established . A total of 733 kidney transplant recipients who were seen for a routine visit at this transplant clinic in 1996 to 1998 were studied prospect ively . During that visit , clinical information was collected and blood was drawn for laboratory evaluation . Information on the previous transplant procedure and the organ donor was obtained from the Eurotransplant Foundation data base . Patients were followed prospect ively using the Austrian Dialysis and Transplant Registry . With the use of proportional-hazards regression , the independent relations of fasting plasma tHcy levels to the risk of death from any cause and kidney allograft loss were examined . During a median follow-up of 6.1 yr , 154 participants died and 260 kidney allografts were lost . After adjustment for several important risk factors , elevated tHcy levels ( > /=12 micromol/L ) were associated with 2.44 times the mortality risk of patients with normal tHcy levels ( hazards ratio 2.44 ; 95 % confidence interval 1.45 to 4.12 ; P < 0.001 ) . Similarly , elevated tHcy levels were associated with 1.63 times increased risk of kidney allograft loss ( hazards ratio 1.63 ; 95 % confidence interval 1.09 to 2.44 ; P = 0.02 ) . In this single-center sample , baseline fasting plasma tHcy levels were independently associated with the risk of death and kidney allograft loss . The clinical utility of homocysteine-lowering therapy , such as multivitamin therapy , to reduce the rates of these end points needs to be studied Homocysteine is a risk factor for atherosclerosis in the general population , and serum homocysteine levels are almost universally elevated in chronic renal failure patients . When such patients are treated with dialysis , cardiovascular disease accounts for more than 50 % of their mortality , which , in some proportion , may be pathophysiologically related to the elevated serum homocysteine levels . From April 2003 to March 2005 , we conducted a 2-year , double-blind , r and omized , placebo-controlled trial of 186 patients with end-stage kidney disease due to any cause , who were older than 18 years and stable on hemodialysis . Patients were assigned to receive either oral folic acid 10 mg 3 times a week immediately after every dialysis session under nurse supervision or an identical-appearing placebo for the entire study . On admission , plasma total homocysteine ( tHcy ) levels were above 13.9 micromol/L in 96.7 % of patients ( median 25.0 micromol/L , range 9.3 - 104.0 micromol/L ) . In the placebo group , tHcy levels remained elevated at 6 , 12 , and 24 months , while oral folate significantly decreased tHcy to a median value of 10.5 ( 2.8 - 20.3 ) micromol/L , ( p<0.01 ) . During the study , 38 patients ( folic acid group 17 vs. placebo group 21 ; p=0.47 ) died from cardiovascular disease . Kaplan-Meier life table analysis dealing with the incidence of cardiovascular events , both fatal and nonfatal ( myocardial infa rct ion , arrhythmias , angina , heart failure , cerebrovascular accident ) , showed that 2 years of folic acid treatment and the lowering of the homocysteine blood levels had no effect on cardiovascular events ( p=0.41 ; hazard ratio 1.24 , 95 % CI 0.74 - 2.10 ) . However , the carotid artery intima-media wall thickness measured in a blinded fashion decreased from 1.94 + /- 0.59 mm to 1.67 + /- 0.38 mm ( p<0.01 ) after 2 years of folate therapy . In this short-term study of uremic patients , 2 years of folic acid supplementation normalized the tHcy blood levels in 92.3 % of patients but did not change the incidence of cardiovascular events compared with the control group . However , ultrasonography of the common carotid arteries performed at entry and 24 months later showed a significant decrease in intima-media thickness with folate supplementation . This suggests that early folate supplementation may benefit patients with chronic renal failure by preventing cardiovascular deterioration The aim of this study was to document , in hyperhomocysteinemic renal transplant recipients , the effect of vitamin supplementation on carotid intima-media thickness ( cIMT ) . Fifty-six hyperhomocysteinemic stable renal transplant recipients were r and omly assigned to either vitamin supplementation ( group A ) or placebo treatment ( group B ) . All patients underwent high-resolution B mode ultrasound to measure IMT of common carotid arteries before and after 6 months of vitamin supplementation . In group A , cIMT significantly decreased after treatment , whereas no significant changes were observed in group B. In conclusion , our results demonstrate a beneficial effect of the treatment of hyperhomocysteinemia by vitamin supplementation on an early sign of atherosclerosis in a group of renal transplant recipients CONTEXT Plasma homocysteine level has been recognized as an important cardiovascular risk factor that predicts adverse cardiac events in patients with established coronary atherosclerosis and influences restenosis rate after percutaneous coronary intervention . OBJECTIVE To evaluate the effect of homocysteine-lowering therapy on clinical outcome after percutaneous coronary intervention . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind placebo-controlled trial involving 553 patients referred to the University Hospital in Bern , Switzerl and , from May 1998 to April 1999 and enrolled after successful angioplasty of at least 1 significant coronary stenosis ( > or = 50 % ) . INTERVENTION Participants were r and omly assigned to receive a combination of folic acid ( 1 mg/d ) , vitamin B12 ( cyanocobalamin , 400 micro g/d ) , and vitamin B6 ( pyridoxine hydrochloride , 10 mg/d ) ( n = 272 ) or placebo ( n = 281 ) for 6 months . MAIN OUTCOME MEASURE Composite end point of major adverse events defined as death , nonfatal myocardial infa rct ion , and need for repeat revascularization , evaluated at 6 months and 1 year . RESULTS After a mean ( SD ) follow-up of 11 ( 3 ) months , the composite end point was significantly lower at 1 year in patients treated with homocysteine-lowering therapy ( 15.4 % vs 22.8 % ; relative risk [ RR ] , 0.68 ; 95 % confidence interval [ CI ] , 0.48 - 0.96 ; P = .03 ) , primarily due to a reduced rate of target lesion revascularization ( 9.9 % vs 16.0 % ; RR , 0.62 ; 95 % CI , 0.40 - 0.97 ; P = .03 ) . A nonsignificant trend was seen toward fewer deaths ( 1.5 % vs 2.8 % ; RR , 0.54 ; 95 % CI , 0.16 - 1.70 ; P = .27 ) and nonfatal myocardial infa rct ions ( 2.6 % vs 4.3 % ; RR , 0.60 ; 95 % CI , 0.24 - 1.51 ; P = .27 ) with homocysteine-lowering therapy . These findings remained unchanged after adjustment for potential confounders . CONCLUSION Homocysteine-lowering therapy with folic acid , vitamin B12 , and vitamin B6 significantly decreases the incidence of major adverse events after percutaneous coronary intervention Background . We previously demonstrated among renal-transplant recipients ( RTRs ) a high prevalence of hyperhomocysteinemia , which might account for their elevated cardiovascular risk . The purpose of our study was to document , in hyperhomocysteinemic RTRs , the effect of vitamin supplementation on carotid intima-media thickness ( cIMT ) , which is an early sign of atherosclerosis . Methods . A total of 56 stable hyperhomocysteinemic RTRs were r and omly assigned to vitamin supplementation ( folic acid 5 mg/day ; vitamin B6 50 mg/day ; vitamin B12 400 & mgr;g ) ( group A ) or placebo treatment ( group B ) for 6 months . All subjects underwent cardiovascular risk-factor assessment , including fasting homocysteine ( Hcy ) levels assay , and high resolution B-mode ultrasound to measure the intima-media thickness of common carotid arteries , at time of enrollment and after 6 months . Results . Fasting Hcy levels markedly decreased in group A after treatment ( 21.8 [ 15.5–76.6 ] & mgr;mol/L vs. 9.3 [ 5.8–13 ] & mgr;mol/L;P < 0.0001 ) , whereas no significant changes were observed in group B ( 20.5 [ 17–37.6 ] & mgr;mol/L vs. 20.7 [ 15–34 ] & mgr;mol/L;P = not significant ) . In group A , cIMT significantly decreased after treatment ( 0.95±0.20 mm vs. 0.64±0.17 mm;P < 0.0001 ) . All except one patient showed a reduction of cIMT and the mean percentage of cIMT decrease was −32.2±12.9 % . Patients with methylenetetrahydrofolate reductase ( MTHFR ) C677 T + /+ genotype , with higher Hcy levels , had the major percentage of decrease of Hcy with respect to the other genotypes ( mean decrease : MTHFR + /+ 74.8±5.7 % ; MTHFR ± 58.1±10 % ; MTHFR −/− 56.3±8.6 % ) . In hyperhomocysteinemic patients without vitamin supplementation ( group B ) we documented a significant increase in cIMT after 6 months ( 0.71±0.16 mm vs. 0.87±0.19 mm;P < 0.05 ) . In 19 of 28 subjects we observed an increase in cIMT , and in 9 of 28 the cIMT was unmodified . The mean percentage of cIMT increase was + 23.3±21.1 % . Conclusions . Our results demonstrate a beneficial effect of the treatment of hyperhomocysteinemia by vitamin supplementation on cIMT in a group of RTRs High serum total homocysteine ( tHcy ) is gaining scrutiny as a risk factor for cardiovascular disease in the general population . The relationship between tHcy and mortality and cardiovascular events in patients with end-stage renal disease ( ESRD ) is unsettled . This r and omized trial evaluates the efficacy of high-dose folic acid in preventing events in ESRD . A total of 510 patients on chronic dialysis were r and omized to 1 , 5 , or 15 mg of folic acid contained in a renal multivitamin with a median follow-up of 24 mo . Mortality , cardiovascular events , and homocysteine levels were assessed . There were 189 deaths , and 121 patients experienced at least one cardiovascular event . Composite rates of mortality and cardiovascular events among the folic acid groups did not differ ( at 24 mo : 43.7 % in 1 mg group , 38.6 % in 5 mg group , 47.1 % in 15 mg group ; log-rank P = 0.47 ) . Unexpectedly , high baseline tHcy was associated with lower event rates . From lowest to highest quartile , event rates at 24 mo were 54.5 % for Q1 , 41.8 % for Q2 , 41.2 % for Q3 , and 34.7 % for Q4 ( log-rank P = 0.033 ) . In contrast to some studies describing tHcy as a risk factor for mortality and cardiovascular events , this study found a reverse relationship between tHcy and events in ESRD patients . Administration of high-dose folic acid did not affect event rates CONTEXT High plasma homocysteine levels are a risk factor for mortality and vascular disease in observational studies of patients with chronic kidney disease . Folic acid and B vitamins decrease homocysteine levels in this population but whether they lower mortality is unknown . OBJECTIVE To determine whether high doses of folic acid and B vitamins administered daily reduce mortality in patients with chronic kidney disease . DESIGN , SETTING , AND PARTICIPANTS Double-blind r and omized controlled trial ( 2001 - 2006 ) in 36 US Department of Veterans Affairs medical centers . Median follow-up was 3.2 years for 2056 participants aged 21 years or older with advanced chronic kidney disease ( estimated creatinine clearance < or = 30 mL/min ) ( n = 1305 ) or end-stage renal disease ( n = 751 ) and high homocysteine levels ( > or = 15 micromol/L ) . INTERVENTION Participants received a daily capsule containing 40 mg of folic acid , 100 mg of pyridoxine hydrochloride ( vitamin B6 ) , and 2 mg of cyanocobalamin ( vitamin B12 ) or a placebo . MAIN OUTCOME MEASURES The primary outcome was all-cause mortality . Secondary outcomes included myocardial infa rct ion ( MI ) , stroke , amputation of all or part of a lower extremity , a composite of these 3 plus all-cause mortality , time to initiation of dialysis , and time to thrombosis of arteriovenous access in hemodialysis patients . RESULTS Mean baseline homocysteine level was 24.0 micromol/L in the vitamin group and 24.2 micromol/L in the placebo group . It was lowered 6.3 micromol/L ( 25.8 % ; P < .001 ) in the vitamin group and 0.4 micromol/L ( 1.7 % ; P = .14 ) in the placebo group at 3 months , but there was no significant effect on mortality ( 448 vitamin group deaths vs 436 placebo group deaths ) ( hazard ratio [ HR ] , 1.04 ; 95 % CI , 0.91 - 1.18 ) . No significant effects were demonstrated for secondary outcomes or adverse events : there were 129 MIs in the vitamin group vs 150 for placebo ( HR , 0.86 ; 95 % CI , 0.67 - 1.08 ) , 37 strokes in the vitamin group vs 41 for placebo ( HR , 0.90 ; 95 % CI , 0.58 - 1.40 ) , and 60 amputations in the vitamin group vs 53 for placebo ( HR , 1.14 ; 95 % CI , 0.79 - 1.64 ) . In addition , the composite of MI , stroke , and amputations plus mortality ( P = .85 ) , time to dialysis ( P = .38 ) , and time to thrombosis in hemodialysis patients ( P = .97 ) did not differ between the vitamin and placebo groups . CONCLUSION Treatment with high doses of folic acid and B vitamins did not improve survival or reduce the incidence of vascular disease in patients with advanced chronic kidney disease or end-stage renal disease . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00032435 OBJECTIVES The Atherosclerosis and Folic Acid Supplementation Trial ( ASFAST ) aim ed to establish whether high-dose folic acid would slow the progression of atherosclerosis and reduce cardiovascular events in patients with chronic renal failure ( CRF ) . BACKGROUND Hyperhomocysteinemia is a potential contributor to the high rates of cardiovascular morbidity and mortality in patients with CRF . METHODS A total of 315 subjects with CRF , mean age 57 years ( range 24 to 79 years ) were r and omized to 15 mg folic acid daily or placebo and followed for a median of 3.6 years . The primary intima-media thickness ( IMT ) and clinical end points were : rate of progression of mean maximum carotid IMT and a composite of myocardial infa rct ion ( MI ) , stroke , and cardiovascular death . Secondary end points included all cardiovascular events and change in pulse wave velocity , systemic arterial compliance and augmentation index . Data were analyzed by intention-to-treat . RESULTS Plasma total homocysteine was reduced by 19 % in the folic acid group . There was no significant difference between the treatment groups in rate of change of IMT or any measure of artery function . Seventy-seven events occurred in the folic acid group ( 14.9 per 100 patient-years ) as compared with 86 in the placebo group ( 16.3 per 100 patient-years ) . The rates of the primary and secondary clinical end points at five years were not significantly different after adjustment for baseline differences between the groups ( adjusted hazard ratio for MI , stroke , and cardiovascular death : 0.98 [ 95 % confidence interval : 0.66 to 1.47 ] ; p = 0.94 ; for all cardiovascular events : 0.95 [ 95 % confidence interval : 0.69 to 1.30 ] ; p = 0.75 ) . CONCLUSIONS High-dose folic acid does not slow atheroma progression or improve cardiovascular morbidity or mortality in patients with CRF Regular physical activity is usually associated with significant health benefits , but therapeutic exercise is seldom routine in renal transplant recipients . We report a r and omized clinical trial of exercise training after renal transplantation . Sixty-nine patients were r and omly recruited on the first or second day after kidney transplantation into two groups : exercise intervention ( PT ) and st and ard care ( CT ) as controls . The exercise training program consisted of tailored exercises to be performed under a physiotherapist 's supervision for 15 to 30 minutes every second hospital day . At that time , biochemical markers of graft function were assessed including specific tests for atherosclerosis . Repeated measures analysis of variance was performed to determine differences between the two groups . We found an inverse correlation between total homocysteine as well as interleukin-18 ( IL:18 ) levels and muscle strength of the upper limbs ( r = -.78 , P < .0001 ) . There was a positive correlation between muscle strength and improved graft function in the PT group versus CT groups ( r = .05 ; P < .05 ) . Hyperhomocysteinemia and high IL-18 expression in renal allograft recipients may be independent markers of early atherosclerosis development Despite reduced risk of acute rejection and increased 1-year graft survival with modern immunosuppressive regimens , chronic allograft nephropathy and death with a functioning graft remain major causes of allograft loss beyond the first year post-transplant . Anti-rejection agents may influence renal transplant outcome not solely through their immunosuppressive activity but also through their effects on other prognostic risk factors . We have analysed 6-year follow-up data from 232 renal transplant recipients r and omized to treatment with tacrolimus or cyclosporin microemulsion at the University Hospital of Wales , Cardiff . Tacrolimus-based therapy was associated with a more favourable cardiovascular risk profile than therapy with cyclosporin microemulsion , with an improved lipid profile , lower arterial blood pressure and lower homocysteine levels . Renal function at 1-year post-transplant is probably the most significant factor influencing long-term graft survival . In our analyses , renal function determined by the glomerular filtration rate was significantly better in tacrolimus-treated patients from month 3 post-transplant . Moreover , normal renal function was maintained throughout a 5-year follow-up in a significantly higher proportion of non-rejecting patients treated with tacrolimus than with cyclosporin microemulsion ( 58 versus 10 % , respectively , at 5 years ; P=0.002 ) . Morphometric analysis of protocol biopsies revealed that the degree of interstitial fibrosis , similar in both treatment groups at baseline , was significantly greater in the cyclosporin microemulsion group over 12 months . Importantly , patients receiving tacrolimus had significantly greater 6-year graft survival ( 81 versus 60 % , P=0.0496 ) and a higher projected graft half-life ( 15 versus 10 years ) than those receiving cyclosporin microemulsion . Tacrolimus treatment is associated with a significantly better cardiovascular risk profile and superior renal function compared with cyclosporin microemulsion treatment , which appears to translate into improved long-term graft survival BACKGROUND Hyperhomocysteinemia , a putative atherothrombotic risk factor , is observed in at least 85 % of patients undergoing maintenance hemodialysis ( HD ) , as well as 65 to 70 % of renal transplant recipients ( RTRs ) . The hyperhomocysteinemia regularly found in HD patients is largely refractory to combined oral vitamin B supplementation featuring supraphysiological doses of folic acid ( FA ) . Relative to their HD counterparts , the hyperhomocysteinemia of RTRs appears to be considerably less refractory to treatment with high-dose FA-based vitamin B supplementation regimens , although controlled comparison data are lacking . We evaluated whether improved total homocysteine (tHcy)-lowering efficacy could be achieved in chronic HD patients with a high-dose L-5-methyltetrahydrofolate (MTHF)-based regimen , as suggested by recent uncontrolled findings , and compared the relative responsiveness of RTRs and HD patients with equivalent baseline tHcy levels , to 12 weeks of tHcy lowering with combined folate-based vitamin B treatment . METHODS First , we blocked r and omized 50 chronic , stable HD patients based on their screening predialysis tHcy levels , sex , and dialysis center into two groups of 25 subjects treated for 12 weeks with oral FA at 15 mg/day , or an equimolar amount ( 17 mg/day ) of oral MTHF . All 50 subjects also received 50 mg/day of oral vitamin B6 and 1.0 mg/day of oral vitamin B12 . RESULTS The mean percentage ( % ) reductions ( + /- 95 % confidence intervals ) in predialysis tHcy were not significantly different [ MTHF 17.0 % ( 12.0 to 22.0 % ) , FA 14.8 % ( 9.6 to 20.1 % ) , P = 0.444 by matched analysis of covariance adjusted for pretreatment tHcy ] . Final on-treatment values ( mean with 95 % confidence interval ) were : MTHF , 20.0 micromol/L ( 18.8 to 21.2 ) ; and FA , 19.5 micromol/L ( 18.3 to 20.7 ) . Moreover , neither treatment result ed in " normalization " of tHcy levels ( that is , final on-treatment values < 12 micromol/L ) among a significantly different or clinical ly meaningful number of patients [ MTHF , 2 out of 25 ( 8 % ) ; FA , 0 out of 25 ( 0 % ) ; Fisher 's exact test of between groups difference , P = 0.490 ] . Second , we compared the relative responsiveness of ( N = 10 ) RTRs and ( N = 39 ) HD patients with equivalent baseline tHcy levels ( RTR range of 14.2 to 23.6 micromol/L , and HD range of 14.4 to 24.9 micromol/L ) to 12 weeks of tHcy-lowering treatment . The RTRs received 2.4 mg/day of FA , 50.0 mg/day of vitamin B6 , and 0.4 mg/day of vitamin B12 , while the HD patients received 15 mg/day of FA or an equimolar amount ( 17 mg/day ) of the reduced folate , MTHF , in addition to 50.0 mg/day of vitamin B6 and 1.0 mg/day of vitamin B12 . The mean percentage ( % ) reductions ( + /- 95 % confidence interval ) in tHcy were as follows : RTR 28.1 % ( 16.2 to 40.0 % ) ; HD 12.1 % ( 6.6 to 17.7 % , P = 0.027 for comparison of between groups differences by analysis of covariance adjusted for baseline tHcy levels ) . Moreover , 5 out of 10 ( 50.0 % ) of the RTR versus only 2 out of 39 ( 5.1 % ) of the HD patients had final on-treatment tHcy levels < 12 micromol/L ( P = 0.002 for comparison of between groups differences by Fisher 's exact test ) . CONCLUSIONS First , in comparison to high-dose FA , high-dose oral MTHF-based supplementation does not afford improved tHcy-lowering efficacy among HD patients . The preponderance of HD patients ( that is , > 90 % ) exhibits mild hyperhomocysteinemia refractory to treatment with either regimen . This treatment refractoriness is not related to defects in folate absorption or circulating plasma and tissue distribution . Second , relative to RTR with comparable baseline tHcy levels , the mild hyperhomocysteinemia of maintenance HD patients is much more refractory to tHcy-lowering vitamin B treatment regimens featuring supraphysiological amounts of FA or the reduced folate MTHF . Accordingly , RTRs are a preferable target population for controlled clinical trials testing the hypothesis that tHcy-lowering vitamin B intervention may reduce arteriosclerotic cardiovascular disease event rates in patients with chronic renal disease |
12,903 | 27,262,287 | Conclusions The present study suggests that TKA patients who receive ACB can achieve similar or even better recovery of quadriceps strength and mobilization ability than those treated with FNB .
Taken as a whole , ACB may be a better analgesia strategy after TKA at present | Purpose Although several studies have compared the clinical efficacy of an adductor canal block ( ACB ) to that of a femoral nerve block ( FNB ) for analgesia after total knee arthroplasty ( TKA ) , disputes mainly exist in the recovery of quadriceps strength and mobilization ability between the two methods .
The aim of the present study was to compare , in a systematic review and meta- analysis , the clinical efficacy of ACB with that of FNB . | Background and Objectives Femoral nerve block ( FNB ) , a commonly used postoperative pain treatment after total knee arthroplasty ( TKA ) , reduces quadriceps muscle strength essential for mobilization . In contrast , adductor canal block ( ACB ) is predominately a sensory nerve block . We hypothesized that ACB preserves quadriceps muscle strength as compared with FNB ( primary end point ) in patients after TKA . Secondary end points were effects on morphine consumption , pain , adductor muscle strength , morphine-related complications , and mobilization ability . Methods We performed a double-blind , r and omized , controlled study of patients scheduled for TKA with spinal anesthesia . The patients were r and omized to receive either a continuous ACB or an FNB via a catheter ( 30-mL 0.5 % ropivacaine given initially , followed by a continuous infusion of 0.2 % ropivacaine , 8 mL/h for 24 hours ) . Muscle strength was assessed with a h and held dynamometer , and we used the percentile change from baseline for comparisons . The trial was registered at clinical trials.gov ( Identifier : NCT01470391 ) . Results We enrolled 54 patients , of which 48 were analyzed . Quadriceps strength as a percentage of baseline was significantly higher in the ACB group compared with the FNB group : ( median [ range ] ) 52 % [ 31–71 ] versus 18 % [ 4–48 ] , ( 95 % confidence interval , 8–41 ; P = 0.004 ) . There was no difference between the groups regarding morphine consumption ( P = 0.94 ) , pain at rest ( P = 0.21 ) , pain during flexion of the knee ( P = 0.16 ) , or adductor muscle strength ( P = 0.39 ) ; neither was there a difference in morphine-related adverse effects or mobilization ability ( P > 0.05 ) . Conclusions Adductor canal block preserved quadriceps muscle strength better than FNB , without a significant difference in postoperative pain Purpose Providing effective analgesia for total knee arthroplasty ( TKA ) patients remains challenging . Femoral nerve block ( FNB ) offers targeted pain control ; however , its effect on motor function , related fall risk and impact on rehabilitation has been the source of controversy . Adductor canal block ( ACB ) potentially spares motor fibres of the femoral nerve , but the comparative effect of the two approaches has not yet been well defined due to considerable variability in pain perception . Our study compares both single-shot FNB and ACB , side to side , in the same patients undergoing bilateral TKA . Methods Sixty patients scheduled for bilateral TKA were r and omised to receive ultrasound-guided FNB on one leg and ACB on the other , in addition to combined spinal epidural anaesthesia . The primary outcome was comparative postoperative pain in either extremity at six to eight , 24 and 48 hours postoperatively . Secondary comparative outcomes included motor strength ( manually and via dynamometer ) , physical therapy milestones and patient satisfaction . Results While pain levels were lowest at six to eight hours postoperatively and increased thereafter ( P < 0.001 ) , no significant differences were seen between extremities at any time point with regard to pain in the quantitative comparison using visual analogue scale ( VAS ) scores ( P = 0.4154 ) , motor strength ( P = 0.7548 ) , physical therapy milestones or patient satisfaction . However , in the qualitative comparison , a significant proportion of patients reported the leg receiving ACB to be more painful than that receiving FNB at 24 h [ 50.9 % ( n = 30 ) vs 25.42 % ( n = 15 ) , P = 0.0168 ) ] . Conclusions Although we could not confirm a benefit in motor function between ACB and FNB , given the equivalent analgesic potency combined with its potentially lower overall impact if neuropraxia should occur , ACB may represent an attractive alternative to FNB Background There are several methods for postoperative analgesia for knee surgery . The commonly utilized method is multimodal analgesia based on continuous femoral nerve block . The aim of this study was to investigate the application of continuous adductor canal block for analgesia after total knee replacement and compare this method with continuous femoral nerve block . Methods Sixty patients scheduled for total knee replacement from June 2013 to March 2014 were r and omly divided into a femoral group and an adductor group . Catheters were placed under the guidance of nerve stimulation in the femoral group and under the guidance of ultrasound in the adductor group . Operations were performed under combined spinal and epidural anesthesia . After the operations , 0.2 % ropivacaine was given at a speed of 5 ml/h through catheters in all patients . Visual analogue scale ( VAS ) pain scores at rest and while moving were noted at 4 , 24 , and 48 hours after the operation , and quadriceps strength was also assessed at these time‐points . Secondary parameters such as doses of complementary analgesics and side effects were also recorded . Results There were no significant differences between the groups in VAS pain scores at rest or while moving , at 4 , 24 , or 48 hours after the operation ( P > 0.05 ) . At these time‐points , mean quadriceps strengths in the adductor group were 3.0 ( 2.75‐3.0 ) , 3.0 ( 3.0‐4.0 ) , and 4.0 ( 3.0‐4.0 ) , respectively , all of which were significantly stronger than the corresponding means in the femoral group , which were 2.0 ( 2.0‐3.0 ) , 2.0 ( 2.0‐3.0 ) , and 3.0 ( 2.0‐4.0 ) , respectively ( P < 0.05 ) . There were no significant differences between the groups in doses of complementary analgesics or side effects ( P > 0.05 ) . X‐ray images of some patients showed that local anesthetic administered into the adductor canal could diffuse upward and reach the femoral triangle . Conclusions Continuous adductor canal block with 0.2 % ropivacaine could be used effectively for analgesia after total knee replacement . Compared with continuous femoral nerve block , this analgesic method has similar analgesic effects and is associated with less weakness of quadriceps muscle Background : This prospect i ve double-blinded , r and omized controlled trial compared adductor canal block ( ACB ) with femoral nerve block ( FNB ) in patients undergoing total knee arthroplasty . The authors hypothesized that ACB , compared with FNB , would exhibit less quadriceps weakness and demonstrate noninferior pain score and opioid consumption at 6 to 8 h postanesthesia . Methods : Patients received an ACB or FNB as a component of a multimodal analgesic . Quadriceps strength , pain score , and opioid consumption were assessed on both legs preoperatively and at 6 to 8 , 24 , and 48 h postanesthesia administration . In a joint hypothesis test , noninferiority was first evaluated on the primary outcomes of strength , pain score , and opioid consumption at 6 to 8 h ; superiority on each outcome at 6 to 8 h was then assessed only if noninferiority was established . Results : Forty-six patients received ACB ; 47 patients received FNB . At 6 to 8 h postanesthesia , ACB patients had significantly higher median dynamometer readings versus FNB patients ( median [ interquartile range ] , 6.1 kgf [ 3.5 , 10.9 ] ( ACB ) vs. 0 kgf [ 0.0 , 3.9 ] ( FNB ) ; P < 0.0001 ) , but was not inferior to FNB with regard to Numeric Rating Scale pain scores ( 1.0 [ 0.0 , 3.5 ] ACB vs. 0.0 [ 0.0 , 1.0 ] FNB ; P = 0.019 ) , or to opioid consumption ( 32.2 [ 22.4 , 47.5 ] ACB vs. 26.6 [ 19.6 , 49.0 ] ; P = 0.0115 ) . At 24 and 48 h postanesthesia , there was no significant statistical difference in dynamometer results , pain scores , or opioid use between the two groups . Conclusion : At 6 to 8 h postanesthesia , the ACB , compared with the FNB , exhibited early relative sparing of quadriceps strength and was not inferior in both providing analgesia or opioid intake Total knee replacement ( TKR ) produces severe postoperative pain . Peripheral nerve blocks can be used as analgesic adjuncts for TKR , but the efficacy of femoral nerve blocks alone is controversial . The sciatic nerve innervates posterior regions of the knee ; thus , performance of both sciatic and femoral nerve blocks may be necessary to improve analgesia after TKR . We performed this study to determine whether peripheral nerve blocks improve analgesia after TKR . In a r and omized , double-blind fashion , 36 patients undergoing TKR received either femoral , sciatic-femoral , or sham nerve blocks after a st and ardized spinal anesthetic . Further postoperative analgesia was provided by patient-controlled IV morphine and ketorolac . Pain at rest and with physical therapy , morphine use , nausea , pruritus , sedation , and patient satisfaction were assessed . Patients receiving peripheral nerve blocks reported better analgesia at rest for at least 8 h after transfer to the hospital ward ( P < 0.05 ) . Morphine use was decreased by approximately 50 % in the peripheral nerve block groups until the second postoperative day ( P < 0.02 ) . Side effect profiles and patient satisfaction were similar between groups . We conclude that femoral nerve blocks improve analgesia and decrease morphine use after TKR . The addition of a sciatic nerve block to the femoral nerve block did not further improve analgesic efficacy . Implication s : Performance of femoral nerve blocks improves analgesia and decreases the need for morphine after total knee replacement surgery . The addition of a sciatic nerve block to the femoral nerve block does not provide additional benefits . ( Anesth Analg 1998;87:93 - 7 Background and Objectives Adductor canal block ( ACB ) has been suggested as an analgesic alternative to femoral nerve block ( FNB ) for procedures on the knee , but its effect on quadriceps motor function is unclear . We performed a r and omized , blinded study to compare quadriceps strength following adductor canal versus FNB in volunteers . Our hypothesis was that quadriceps strength would be preserved following ACB , but not FNB . Secondary outcomes included relative preservation of hip adduction and degree of balance impairment . Methods The ACB was performed in one leg and the FNB in the contralateral leg in 16 volunteers using a r and omized block sequence . For all blocks , 15 mL of 3 % chloroprocaine was injected under ultrasonographic guidance . Maximal voluntary isometric contraction of knee extension and hip adduction was measured at baseline and at 30 and 60 minutes after block . After 60-minute assessment s were complete , the second block was placed . A test of balance ( Berg Balance Scale ) was performed 30 minutes after the first block only . Results Quadriceps strength and balance scores were similar to baseline following ACB . Following FNB , there was a significant reduction in quadriceps strength ( 95.1 % ± 17.1 % vs 11.1 % ± 14.0 % ; P < 0.0001 ) and balance scores ( 56 ± 0 vs 37 ± 17.2 ; P = 0.02 ) compared with baseline . There was no difference in hip adductor strength ( 97.0 % ± 10.8 % vs 91.8 % ± 9.6 % ; P = 0.17 ) . Conclusions Compared with FNB , ACB results in significant quadriceps motor sparing and significantly preserved balance Background : Whether decreasing the local anesthetic concentration during a continuous femoral nerve block results in less quadriceps weakness remains unknown . Methods : Preoperatively , bilateral femoral perineural catheters were inserted in subjects undergoing bilateral knee arthroplasty ( n = 36 ) at a single clinical center . Postoperatively , right-sided catheters were r and omly assigned to receive perineural ropivacaine of either 0.1 % ( basal 12 ml/h ; bolus 4 ml ) or 0.4 % ( basal 3 ml/h ; bolus 1 ml ) , with the left catheter receiving the alternative concentration/rate in an observer- and subject-masked fashion . The primary endpoint was the maximum voluntary isometric contraction of the quadriceps femoris muscles the morning of postoperative day 2 . Equivalence of treatments would be concluded if the 95 % CI for the difference fell within the interval −20%–20 % . Secondary endpoints included active knee extension , passive knee flexion , tolerance to cutaneous electrical current applied over the distal quadriceps tendon , dynamic pain scores , opioid requirements , and ropivacaine consumption . Results : Quadriceps maximum voluntary isometric contraction for limbs receiving 0.1 % ropivacaine was a mean ( SD ) of 13 ( 8) N · m , versus 12 ( 8) N · m for limbs receiving 0.4 % [ intrasubject difference of 3 ( 40 ) percentage points ; 95 % CI −10–17 ; P = 0.63 ] . Because the 95 % CI fell within prespecified tolerances , we conclude that the effect of the two concentrations were equivalent . Similarly , there were no statistically significant differences in secondary endpoints . Conclusions : For continuous femoral nerve blocks , we found no evidence that local anesthetic concentration and volume influence block characteristics , suggesting that local anesthetic dose ( mass ) is the primary determinant of perineural infusion effects UNLABELLED Total knee arthroplasty is associated with intense , early post-operative pain . Femoral nerve block is known to provide optimal pain relief but reduces the strength of the quadriceps muscle and associated with the risk of falling . Adductor canal block is almost pure sensory blockade with minimal effect on quadriceps muscle strength . We prospect ively r and omized 100 patients in two groups ' continuous adductor and femoral block group . Ambulation ability ( Timed up go , 10-m walk , 30 s chair test ) , time to active SLR , quadsticks , staircase competency , ambulation distance was significantly better ( P value < 0.001 ) in adductor canal group whereas pain scores , opioid consumption showed no significant difference . Adductor canal block provided better ambulation and early functional recovery but without superior analgesia than femoral nerve block post TKA . LEVEL OF EVIDENCE Level III , therapeutic study BACKGROUND : Continuous peripheral nerve blocks ( CPNB ) may induce muscle weakness , and multiple recently published series emphasize patient falls after postarthroplasty CPNB . However , none have included an adequate control group , and therefore the relationship between CPNB and falls remains speculative . METHODS : We pooled data from 3 previously published , r and omized , triple-masked , placebo-controlled studies of CPNB involving the femoral nerve after knee and hip arthroplasty . RESULTS : No patients receiving perineural saline ( n = 86 ) fell ( 0 % ; 95 % confidence interval [ CI ] = 0%–5 % ) , but there were 7 falls in 6 patients receiving perineural ropivacaine ( n = 85 ; 7 % ; 95 % CI = 3%–15 % ; Fisher 's exact test P = 0.013 ) . CONCLUSIONS : Our analysis suggests that there is a causal relationship between CPNB and the risk of falling after knee and hip arthroplasty In a well‐defined fast‐track setup for total hip and knee arthroplasty , with a multimodal analgesic regimen consisting of intra‐operative local anaesthetic infiltration and oral celecoxib , gabapentin and paracetamol for 6 days postoperatively , we conducted a prospect i ve , consecutive , observational study . The purpose was to describe the prevalence and intensity of subacute postoperative pain and opioid related side effects , use of analgesics and functional ability 1–10 and 30 days postoperatively . Fast‐track total hip and knee arthroplasty with early discharge ( < 3 days ) result ed in acceptable levels of pain and postoperative nausea and vomiting with concomitant low use of opioids in > 95 % of patients after discharge before day 10 after total hip arthroplasty . However , after total knee arthroplasty 52 % patients reported moderate pain ( VAS 30–59 mm ) , and 16 % severe pain ( VAS ≥ 60 mm ) when walking 1 month after surgery with a concomitant increase in the use of strong opioids . These results emphasise the need for improvement in analgesia after discharge following total knee arthroplasty , to facilitate rehabilitation Because both the saphenous nerve and in part the obturator nerve are traversing the adductor canal of the thigh , we hypothesised that repeated administration of a local anaesthetic ( LA ) into this aponeurotic space could be a useful option for post‐operative analgesia after knee replacement surgery . A systematic search of the literature pertinent to the blockade of the saphenous and /or obturator nerves for pain relief after knee surgery was conducted . Further , pain and opioid requirements were evaluated in eight patients receiving a continuous blockade of the saphenous and obturator nerve ( adductor‐canal‐blockade ) after total knee arthroplasty ( TKA ) . Finally , we performed cross‐sectional MR scans of the adductor canal after injection of ropivacaine 30 ml in one patient . The systematic literature search revealed only one controlled study , where selective blockade of the saphenous nerve was investigated for the purpose of clinical pain relief after knee arthroscopy . We located no studies reporting on saphenous and /or obturator nerve block for pain relief after TKA . Preliminary findings in eight patients demonstrated that a continuous adductor‐canal‐blockade for 48 h after TKA was associated with low mean pain scores at rest and low mean requirements for supplemental morphine . MR scans in one patient demonstrated that 30 ml of LA filled the adductor canal , including the distal part , where the posterior branch of the obturator nerve joins the vessels and the saphenous nerve . Continuous adductor‐canal‐blockade may be a valuable adjunct for post‐operative analgesia after major knee surgery . These preliminary results should be confirmed in r and omised , controlled trials |
12,904 | 18,326,601 | Low-GI and /or low-GL diets are independently associated with a reduced risk of certain chronic diseases .
In diabetes and heart disease , the protection is comparable with that seen for whole grain and high fiber intakes .
The findings support the hypothesis that higher postpr and ial glycemia is a universal mechanism for disease progression | BACKGROUND Inconsistent findings from observational studies have prolonged the controversy over the effects of dietary glycemic index ( GI ) and glycemic load ( GL ) on the risk of certain chronic diseases .
OBJECTIVE The objective was to evaluate the association between GI , GL , and chronic disease risk with the use of meta- analysis techniques . | Hyperinsulinemia may explain excess colorectal cancer among individuals who are overweight or inactive . Recent studies have observed elevated colorectal cancer risk among individuals with elevated insulin levels 2 hours after oral glucose challenge or with elevated plasma C-peptide levels . The effect of consuming a high glycemic diet on colorectal risk , however , remains uncertain . Two prospect i ve cohort studies , the Nurses ' Health Study and the Health Professionals Follow-up Study , contributed up to 20 years of follow-up . After exclusions , 1,809 incident colorectal cancers were available for analyses . Dietary glycemic load ( GL ) was calculated as a function of glycemic index ( postpr and ial blood glucose response as compared with a reference food ) , carbohydrate content , and frequency of intake of individual foods reported on food frequency question naires . Multivariable Cox proportional hazards models were used to adjust for potential confounders . Intakes of dietary carbohydrate , GL , overall glycemic index , sucrose , and fructose were not associated with colorectal cancer risk in women . A small increase in risk was observed in men with high dietary GL ( multivariate relative risk , 1.32 ; 95 % confidence interval , 0.98 - 1.79 ; highest versus lowest quintile ) , sucrose or fructose ( multivariate relative risk , 1.37 ; 95 % confidence interval , 1.05 - 1.78 ; highest versus lowest quintile of fructose , P = 0.008 ) . Associations were slightly stronger among men with elevated body mass index ( > or = 25 kg/m(2 ) ) . Results among women were similar after stratifying by body mass index or physical activity . High intakes of GL , fructose , and sucrose were related to an elevated colorectal cancer risk among men . For women , however , these factors did not seem to increase the risk of colorectal cancer OBJECTIVE To examine associations between type 2 diabetes and fiber , glycemic load ( GL ) , dietary glycemic index ( GI ) , and fiber-rich foods . RESEARCH DESIGN AND METHODS This was a prospect i ve study of 36,787 men and women aged 40 - 69 years without diabetes . For all self-reported cases of diabetes at 4-year follow-up , confirmation of diagnosis was sought from medical practitioners . Case subjects were those who reported diabetes at follow-up and for whom there was no evidence that they did not have type 2 diabetes . Data were analyzed with logistic regression , adjusting for country of birth , physical activity , family history of diabetes , alcohol and energy intake , education , 5-year weight change , sex , and age . RESULTS Follow-up was completed by 31,641 ( 86 % ) participants , and 365 cases were identified . The odds ratio ( OR ) for the highest quartile of white bread intake compared with the lowest was 1.37 ( 95 % CI 1.04 - 1.81 ; P for trend = 0.001 ) . Intakes of carbohydrate ( OR per 200 g/day 0.58 , 0.36 - 0.95 ) , sugars ( OR per 100 g/day 0.61 , 0.47 - 0.79 ) , and magnesium ( OR per 500 mg/day 0.62 , 0.43 - 0.90 ) were inversely associated with incidence of diabetes , whereas intake of starch ( OR per 100 g/day 1.47 , 1.06 - 2.05 ) and dietary GI ( OR per 10 units 1.32 , 1.05 - 1.66 ) were positively associated with diabetes . These relationships were attenuated after adjustment for BMI and waist-to-hip ratio . CONCLUSIONS Reducing dietary GI while maintaining a high carbohydrate intake may reduce the risk of type 2 diabetes . One way to achieve this would be to substitute white bread with low-GI breads BACKGROUND Little is known about the effects of the amount and type of carbohydrates on risk of coronary heart disease ( CHD ) . OBJECTIVE The objective of this study was to prospect ively evaluate the relations of the amount and type of carbohydrates with risk of CHD . DESIGN A cohort of 75521 women aged 38 - 63 y with no previous diagnosis of diabetes mellitus , myocardial infa rct ion , angina , stroke , or other cardiovascular diseases in 1984 was followed for 10 y. Each participant 's dietary glycemic load was calculated as a function of glycemic index , carbohydrate content , and frequency of intake of individual foods reported on a vali date d food-frequency question naire at baseline . All dietary variables were up date d in 1986 and 1990 . RESULTS During 10 y of follow-up ( 729472 person-years ) , 761 cases of CHD ( 208 fatal and 553 nonfatal ) were documented . Dietary glycemic load was directly associated with risk of CHD after adjustment for age , smoking status , total energy intake , and other coronary disease risk factors . The relative risks from the lowest to highest quintiles of glycemic load were 1.00 , 1.01 , 1 . 25 , 1.51 , and 1.98 ( 95 % CI : 1.41 , 2.77 for the highest quintile ; P for trend < 0.0001 ) . Carbohydrate classified by glycemic index , as opposed to its traditional classification as either simple or complex , was a better predictor of CHD risk . The association between dietary glycemic load and CHD risk was most evident among women with body weights above average ¿ ie , body mass index ( in kg/m(2 ) ) > /= 23 . CONCLUSION These epidemiologic data suggest that a high dietary glycemic load from refined carbohydrates increases the risk of CHD , independent of known coronary disease risk factors BACKGROUND Dietary carbohydrates may influence the development of type 2 ( non-insulin-dependent ) diabetes , for example , through effects on blood glucose and insulin concentrations . OBJECTIVE We examined the relations of baseline intake of carbohydrates , dietary fiber , dietary magnesium , and carbohydrate-rich foods and the glycemic index with incidence of diabetes . DESIGN This was a prospect i ve cohort study of 35988 older Iowa women initially free of diabetes . During 6 y of follow-up , 1141 incident cases of diabetes were reported . RESULTS Total grain , whole-grain , total dietary fiber , cereal fiber , and dietary magnesium intakes showed strong inverse associations with incidence of diabetes after adjustment for potential nondietary confounding variables . Multivariate-adjusted relative risks of diabetes were 1.0 , 0.99 , 0.98 , 0.92 , and 0.79 ( P for trend : 0.0089 ) across quintiles of whole-grain intake ; 1.0 , 1.09 , 1.00 , 0.94 , and 0.78 ( P for trend : 0.005 ) across quintiles of total dietary fiber intake ; and 1.0 , 0.81 , 0.82 , 0.81 , and 0.67 ( P for trend : 0.0003 ) across quintiles of dietary magnesium intake . Intakes of total carbohydrates , refined grains , fruit and vegetables , and soluble fiber and the glycemic index were unrelated to diabetes risk . CONCLUSION These data support a protective role for grains ( particularly whole grains ) , cereal fiber , and dietary magnesium in the development of diabetes in older women BACKGROUND Metabolism of many of the most commonly consumed carbohydrates in the United States results in a high plasma glucose response , which can be quantified by the glycemic load . Although hyperglycemia is a risk factor for cataract , there is no information on the potential effect of a high dietary glycemic load on the incidence of age-related cataract . OBJECTIVE Our objective was to prospect ively examine the association between dietary glycemic load and incident age-related cataract . DESIGN We studied 2 cohorts-71 919 women and 39 926 men-aged > or = 45 y who had no previous diagnosis of cataract , diabetes mellitus , or cancer and who were followed for 14 and 12 y , respectively , for the occurrence of cataract extraction . We calculated dietary glycemic load from data reported on multiple vali date d food-frequency question naires and used pooled logistic regression models to estimate the association with incident cataract extraction . We performed analyses separately for each cohort and then calculated pooled estimates across cohorts . RESULTS During 980 683 person-years of follow-up , we confirmed 4865 incident age-related cataract extraction s. After adjustment for age , cigarette smoking , body mass index , total caloric intake , dietary intake of lutein and zeaxanthin , and alcohol consumption , there was no significant relation of dietary glycemic load to risk of cataract extraction ( P for trend = 0.10 ) . The pooled relative risk between the highest and lowest quintiles of dietary glycemic load was 0.95 ( 95 % CI : 0.81 , 1.11 ; P for heterogeneity by cohort = 0.1 ) . CONCLUSION These prospect i ve epidemiologic data do not support the hypothesis that a high dietary glycemic load , primarily a result of consumption of refined carbohydrates , increases the risk of cataract extraction BACKGROUND Reducing the glycemic load ( GL ) is considered beneficial for managing insulin resistance . The GL can be reduced either by reducing carbohydrate intake or by reducing the glycemic index ( GI ) . OBJECTIVE We studied whether these 2 dietary maneuvers have the same long-term effects on postpr and ial plasma glucose , insulin , triacylglycerol , and free fatty acid ( FFA ) concentrations in subjects with impaired glucose tolerance ( IGT ) . DESIGN Thirty-four subjects with IGT were r and omly assigned to high-carbohydrate , high-GI ( high-GI ) ; high-carbohydrate , low-GI ( low-GI ) ; and low-carbohydrate , high-monounsaturated fatty acid ( MUFA ) diets for 4 mo . Plasma glucose , insulin , and FFAs were measured from 0800 to 1600 at baseline in response to high-GI meals ( 60 % carbohydrate , GI = 61 , GL = 63 ) and after 4 mo in response to meals representative of the study diet . RESULTS Carbohydrate intake ( % of energy ) , GI , and GL in the high-GI , low-GI , and MUFA groups ( breakfast and lunch meals combined ) , respectively , were 60 % , 61 , and 63 ; 60 % , 53 , and 55 ; and 49 % , 61 , and 52 . Compared with the change after 4 mo of the high-GI diet , both the low-GI and MUFA diets reduced 0 - 8-h mean plasma glucose concentrations by 0.35 mmol/L ( P < 0.05 ) . Mean plasma insulin was approximately 20 % higher ( P < 0.05 ) and FFAs approximately 12 % lower ( P < 0.05 ) after the low-GI diet than after the high-GI diet , with no significant effect of MUFA . Changes in 0 - 8-h mean plasma triacylglycerols in the 3 treatment groups differed significantly : -0.14 , 0.04 , and 0.18 mmol/L , respectively , with the high-GI , MUFA , and low-GI diets . CONCLUSIONS In subjects with IGT , reducing the GI of the diet for 4 mo reduced postpr and ial plasma glucose by the same amount as did reducing carbohydrate intake . The 2 dietary maneuvers had different effects on postpr and ial plasma insulin , triacylglycerols , and FFAs BACKGROUND Increasing evidence suggests an important role of carbohydrate quality in the development of type 2 diabetes . OBJECTIVE Our objective was to prospect ively examine the association between glycemic index , glycemic load , and dietary fiber and the risk of type 2 diabetes in a large cohort of young women . DESIGN In 1991 , 91249 women completed a semiquantitative food-frequency question naire that assessed dietary intake . The women were followed for 8 y for the development of incident type 2 diabetes , and dietary information was up date d in 1995 . RESULTS We identified 741 incident cases of confirmed type 2 diabetes during 8 y ( 716 300 person-years ) of follow-up . After adjustment for age , body mass index , family history of diabetes , and other potential confounders , glycemic index was significantly associated with an increased risk of diabetes ( multivariate relative risks for quintiles 1 - 5 , respectively : 1 , 1.15 , 1.07 , 1.27 , and 1.59 ; 95 % CI : 1.21 , 2.10 ; P for trend = 0.001 ) . Conversely , cereal fiber intake was associated with a decreased risk of diabetes ( multivariate relative risks for quintiles 1 - 5 , respectively : 1 , 0.85 , 0.87 , 0.82 , and 0.64 ; 95 % CI : 0.48 , 0.86 ; P for trend = 0.004 ) . Glycemic load was not significantly associated with risk in the overall cohort ( multivariate relative risks for quintiles 1 - 5 , respectively : 1 , 1.31 , 1.20 , 1.14 , and 1.33 ; 95 % CI : 0.92 , 1.91 ; P for trend = 0.21 ) . CONCLUSIONS A diet high in rapidly absorbed carbohydrates and low in cereal fiber is associated with an increased risk of type 2 diabetes The determine the effect of different foods on the blood glucose , 62 commonly eaten foods and sugars were fed individually to groups of 5 to 10 healthy fasting volunteers . Blood glucose levels were measured over 2 h , and expressed as a percentage of the area under the glucose response curve when the same amount of carbohydrate was taken as glucose . The largest rises were seen with vegetables ( 70 + /- 5 % ) , followed by breakfast cereals ( 65 + /- 5 % ) , cereals and biscuits ( 60 + /- 3 % ) , fruit ( 50 + /- 5 % ) , dairy products ( 35 + /- 1 % ) , and dried legumes ( 31 + /- 3 % ) . A significant negative relationship was seen between fat ( p less than 0.01 ) and protein ( p less than 0.001 ) and postpr and ial glucose rise but not with fiber or sugar content Although diet is believed to influence colorectal cancer risk , the long-term effects of a diet with a high glycemic load are unclear . The growing recognition that colorectal cancer may be promoted by hyperinsulinemia and insulin resistance suggests that a diet inducing high blood glucose levels and an elevated insulin response may contribute to a metabolic environment conducive to tumor growth . We prospect ively followed a cohort of 38 451 women for an average of 7.9 years and identified 174 with incident colorectal cancer . We used baseline dietary intake measurements , assessed with a semiquantitative food-frequency question naire , to examine the associations of dietary glycemic load , overall dietary glycemic index , carbohydrate , fiber , nonfiber carbohydrate , sucrose , and fructose with the subsequent development of colorectal cancer . Cox proportional hazards models were used to estimate relative risks ( RRs ) . Dietary glycemic load was statistically significantly associated with an increased risk of colorectal cancer ( adjusted RR = 2.85 , 95 % confidence interval [ CI ] = 1.40 to 5.80 , comparing extreme quintiles of dietary glycemic load ; P(trend ) = .004 ) and was associated , although not statistically significantly , with overall glycemic index ( corresponding RR = 1.71 , 95 % CI = 0.98 to 2.98 ; P(trend ) = .04 ) . Total carbohydrate ( adjusted RR = 2.41 , 95 % CI = 1.10 to 5.27 , comparing extreme quintiles of carbohydrate ; P(trend ) = .02 ) , nonfiber carbohydrate ( corresponding RR = 2.60 , 95 % CI = 1.22 to 5.54 ; P(trend ) = .02 ) , and fructose ( corresponding RR = 2.09 , 95 % CI = 1.13 to 3.87 ; P(trend ) = .08 ) were also statistically significantly associated with increased risk . Thus , our data indicate that a diet with a high dietary glycemic load may increase the risk of colorectal cancer in women Evidence that the insulin pathway may be involved in breast carcinogenesis has increased the interest in dietary factors that influence insulin secretion and resistance . We investigated dietary carbohydrate , fibre , glycaemic index ( GI ) and glycaemic load ( GL ) in a prospect i ve study of 324 breast cancers diagnosed in 12,273 post‐menopausal women . Although an increase of 1 st and ard deviation in carbohydrate was marginally associated with risk of breast cancer , relative risk ( RR ) 1.31 ( 95 % CI , 0.98 , 1.75 ) , there were no significant associations with fibre , 1.08 ( 0.92 , 1.26 ) , GI , 0.98 ( 0.88 , 1.10 ) or GL , 1.19 ( 0.93 , 1.52 ) or with carbohydrate foods ( bread , rice , pasta ) . The RR for carbohydrate and localized disease was elevated , 1.40 ( 1.02 , 1.92 ) , but like those for fibre , GI and GL did not differ significantly between localized and non‐localized disease . RRs for grade I , but not grade II or III , tumours were elevated for fibre , 1.38 ( 1.08 , 1.75 ) , carbohydrate , 1.56 ( 1.08 , 2.25 ) and GL , 1.41 ( 1.01 , 1.98 ) but not for GI , 0.84 ( 0.65 , 1.09 ) . The RRs for fibre and oestrogen receptor ( ER ) positive ( + ) and progesterone receptor ( PR ) positive ( + ) tumours , 1.36 ( 1.10 , 1.67 ) , differed significantly from those for ER positive ( + ) and PR negative ( − ) tumours , 1.01 ( 0.61 , 1.69 ) and ER−/PR− tumours , 0.65 ( 0.43 , 0.99 ) , p = 0.005 . Our data do not support a strong role for GI and GL in breast carcinogenesis but suggest that increased intake of fibre and carbohydrate may be associated with the diagnosis of cancers of more favourable prognosis . © 2005 Wiley‐Liss , Controversy exists about the optimal amount and source of dietary carbohydrate for managing insulin resistance . Therefore , we compared the effects on insulin sensitivity ( SI ) , pancreatic responsivity ( AIRglu ) and glucose disposition index of dietary advice aim ed at reducing the amount or altering the source of dietary carbohydrate in subjects with impaired glucose tolerance ( IGT ) . Subjects were r and omized to high-carbohydrate-high-glycaemic index ( GI ) ( high-GI , n 11 ) , high-carbohydrate-low-GI ( low-GI , n 13 ) , or low-carbohydrate-high-monounsaturated fat ( MUFA , n 11 ) dietary advice , with SI , AIRglu and DI measured using a frequently sample d , intravenous glucose tolerance test before and after 4 months treatment . Carbohydrate and fat intakes and diet GI , respectively , were : high-GI , 53 % , 28 % , 83 ; low-GI , 55 % , 25 % , 76 ; MUFA , 47 % , 35 % , 82 . Weight changes on each diet differed significantly from each other : high-GI , -0.49 ( sem 0.29 ) kg ; low-GI , -0.19 ( sem 0.40 ) kg ; MUFA + 0.27 ( sem 0.45 ) kg . Blood lipids did not change , but glycated haemoglobin increased significantly on MUFA , 0.02 ( sem 0.11 ) % , relative to low-GI , -0.19 ( sem 0.08 ) % , and high-GI , -0.13 ( sem 0.14 ) % . Diastolic blood pressure fell by 8 mmHg on low-GI relative to MUFA ( P=0.038 ) . Although SI and AIRglu did not change significantly , DI , a measure of the ability of beta-cells to overcome insulin resistance by increasing insulin secretion , increased on low-GI by > 50 % ( P=0.02 ) . After adjusting for baseline values , the increase in DI on low-GI , 0.17 ( sem 0.07 ) , was significantly greater than those on MUFA , -0.09 ( sem 0.08 ) and high-GI , -0.03 ( sem 0.02 ) ( P=0.019 ) . Thus , the long-term effects of altering the source of dietary carbohydrate differ from those of altering the amount . High-carbohydrate-low-GI dietary advice improved beta-cell function in subjects with IGT , and may , therefore , be useful in the management of IGT Dietary fiber , fiber fractions , carbohydrate , glycemic index , and glycemic load were prospect ively assessed five times over 18 years with a vali date d food frequency question naire in relation to breast cancer risk among 88,678 women ( aged 34 - 59 years at baseline ) in the Nurses ' Health Study . Incident breast cancer occurred in 4,092 of these women between 1980 and 1998 . The authors observed no material association between carbohydrate intake , glycemic index and glycemic load , total dietary fiber intake , and breast cancer risk . The relative risks for the highest versus the lowest quintile of intake were 0.97 ( 95 % confidence interval ( CI ) : 0.87 , 1.08 ) for carbohydrates , 1.08 ( 95 % CI : 0.97 , 1.19 ) for glycemic index , 0.99 ( 95 % CI : 0.89 , 1.10 ) for glycemic load , and 0.98 ( 95 % CI : 0.87 , 1.11 ) for fiber . The relative risk comparing those in the highest 0.7 % of fiber intake ( > 30 g/day ) with those in the lowest 10 % of fiber intake ( < or = 10 g/day ) was 0.68 ( 95 % CI : 0.43 , 1.06 ) . Analyses stratified by menopausal status and body mass index also showed no clear risk pattern . In this cohort of middle-aged women , no overall association was found for dietary carbohydrates , glycemic index and glycemic load , and breast cancer risk . This study also confirmed the lack of an overall association between intake of fiber and fiber types and breast cancer risk observed in other prospect i ve studies BACKGROUND There is some evidence that plasma insulin levels might influence ovarian cancer risk . Glycaemic index ( GI ) and glycaemic load ( GL ) are measures that allow the carbohydrate content of individual foods to be classified according to their postpr and ial glycaemic effects and hence their effects on circulating insulin levels . Therefore , we examined ovarian cancer risk in association with GI and GL , and intake of dietary carbohydrate and sugar . METHODS The study was conducted in a prospect i ve cohort of 49 613 Canadian women enrolled in the National Breast Screening Study ( NBSS ) who completed a self-administered food-frequency question naire ( FFQ ) between 1980 and 1985 . Linkages to national mortality and cancer data bases yielded data on deaths and cancer incidence , with follow-up ending between 1998 and 2000 . Data from the FFQ were used to estimate overall GI and GL , and Cox proportional hazards models were used to estimate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) for the association between energy-adjusted quartile levels of GL , overall GI , total carbohydrates , total sugar and ovarian cancer risk . RESULTS During a mean 16.4 years of follow-up , we observed 264 incident ovarian cancer cases . GI and total carbohydrate and sugar intakes were not associated with ovarian cancer risk in the total cohort . GL was positively associated with a 72 % increase in risk of ovarian cancer ( HR=1.72 , 95 % CI=1.13 - 2.62 , Ptrend=0.01 ) and the magnitude of the association was slightly greater among postmenopausal ( HR=1.89 , 95 % CI=0.98 - 3.65 , Ptrend=0.03 ) than among premenopausal women ( HR=1.64 , 95 % CI=0.95 - 2.88 , Ptrend=0.07 ) . CONCLUSIONS Our data suggest that consumption of diets with high GL values may be associated with increased risk of ovarian cancer Mounting evidence suggests that high circulating levels of insulin might be associated with increased colorectal cancer risk . The glycemic effects of diets high in refined starch may increase colorectal cancer risk by affecting insulin and /or insulin-like growth factor-I levels . We examined the association between dietary intake and colorectal cancer risk in a cohort of 49 124 women participating in a r and omized , controlled trial of screening for breast cancer in Canada . Linkages to Canadian mortality and cancer data bases yielded data on mortality and cancer incidence up to December 31 , 2000 . During an average 16.5 years of follow-up , we observed 616 incident cases of colorectal cancer ( 436 colon cancers , 180 rectal cancers ) . Rate ratios for colorectal cancer for the highest versus the lowest quintile level were 1.05 ( 95 % confidence interval [ CI ] = 0.73 to 1.53 ; P(trend ) = .94 ) for glycemic load , 1.01 ( 95 % CI = 0.68 to 1.51 ; P(trend ) = .66 ) for total carbohydrates , and 1.03 ( 95 % CI = 0.73 to 1.44 ; P(trend ) = .71 ) for total sugar . Our data do not support the hypothesis that diets high in glycemic load , carbohydrates , or sugar increase colorectal cancer risk A diet with a high glycemic load ( GL ) may contribute to a metabolic environment that enhances tumorigenesis . Little is known , however , about whether high glycemic diets increase breast cancer risk in women . We examined the associations between baseline measurements of dietary GL and overall glycemic index ( GI ) and subsequent breast cancer in a cohort of 39,876 women , ages 45 years or older , participating in the Women ’s Health Study . During a mean of 6.8 years of follow-up there were 946 confirmed cases of breast cancer . We found no association between dietary GL [ multivariable-adjusted relative risk ( RR ) , 1.01 ; confidence interval ( CI ) , 0.76–1.35 , comparing extreme quintiles ; P for trend = 0.96 ] or overall GI ( corresponding RR , 1.03 ; CI , 0.84–1.28 ; P for trend = 0.66 ) and breast cancer risk in the cohort as a whole . Exploratory analyses stratified by baseline measurements of menopausal status , physical activity , smoking history , alcohol use , and history of diabetes mellitus , hypertension , or hypercholesterolemia showed no significant associations , except in the subgroup of women who were premenopausal and reported low levels of physical activity ( GL multivariable-adjusted RR , 2.35 ; CI , 1.03–5.37 ; P for trend = 0.07 ; GI multivariable-adjusted RR , 1.56 ; CI , 0.88–2.78 ; P for trend = 0.02 , comparing extreme quintiles ) . Although we did not find evidence that a high glycemic diet increases overall breast cancer risk , the increase in risk in premenopausal women with low levels of physical activity suggests the possibility that the effects of a high glycemic diet may be modified by lifestyle and hormonal factors . Prospect i ve studies of a larger sample size and longer duration are warranted to confirm our findings OBJECTIVE High-glycaemic-load diets may increase endometrial cancer risk by increasing circulating insulin levels and , as a consequence , circulating oestrogen levels . Given the paucity of epidemiological data regarding the relationship between dietary glycaemic index and glycaemic load and endometrial cancer risk , we sought to examine these associations using data from a prospect i ve cohort study . DESIGN , SETTING AND SUBJECTS We examined the association between dietary glycaemic load and endometrial cancer risk in a cohort of 49,613 Canadian women aged between 40 and 59 years at baseline who completed self-administered food-frequency question naires between 1982 and 1985 . Linkages to national mortality and cancer data bases yielded data on deaths and cancer incidence , with follow-up ending between 1998 and 2000 . RESULTS During a mean of 16.4 years of follow-up , we observed 426 incident cases of endometrial cancer . Hazard ratios for the highest versus the lowest quartile level of overall glycaemic index and glycaemic load were 1.47 ( 95 % confidence interval ( CI ) = 0.90 - 2.41 ; P for trend = 0.14 ) and 1.36 ( 95 % CI = 1.01 - 1.84 ; P for trend = 0.21 ) , respectively . No association was observed between total carbohydrate or total sugar consumption and endometrial cancer risk . Among obese women ( body mass index > 30 kg m(-2 ) ) the hazard ratio for the highest versus the lowest quartile level of glycaemic load was 1.88 ( 95 % CI = 1.08 - 3.29 ; P for trend = 0.54 ) and there was a 55 % increased risk for the highest versus the lowest quartile level of glycaemic load among premenopausal women . There was also evidence to support a positive association between glycaemic load and endometrial cancer risk among postmenopausal women who had used hormone replacement therapy . CONCLUSIONS Our data suggest that diets with high glycaemic index or high glycaemic load may be associated with endometrial cancer risk overall , and particularly among obese women , premenopausal women and postmenopausal women who use hormone replacement therapy Diets with a high glycemic index and glycemic load have been hypothesized to be implicated in the etiology of colorectal cancer owing to their potential to increase postpr and ial glucose and insulin levels . Prospect i ve data on glycemic index and glycemic load in relation to colorectal cancer risk are limited and inconsistent . Therefore , the authors prospect ively investigated the associations of dietary carbohydrate , glycemic index , and glycemic load with the incidence of colorectal cancer among 61,433 Swedish women who were free of cancer in 1987 - 1990 and completed a 67-item food frequency question naire . During follow-up through June 2005 , 870 incident cases of colorectal adenocarcinoma were diagnosed . Carbohydrate intake , glycemic index , and glycemic load were not associated with risk of colorectal cancer , colon cancer , or rectal cancer . The multivariate hazard ratios for colorectal cancer comparing the highest with the lowest quintile were 1.10 ( 95 % confidence interval : 0.85 , 1.44 ) for carbohydrate intake , 1.00 ( 95 % confidence interval : 0.75 , 1.33 ) for glycemic index , and 1.06 ( 95 % confidence interval : 0.81 , 1.39 ) for glycemic load . Results did not vary by body mass index . The findings from this prospect i ve study do not support the hypothesis that a high carbohydrate intake , a high glycemic index , and a high glycemic load increase the risk of colorectal cancer OBJECTIVE To examine prospect ively the relationship between glycemic diets , low fiber intake , and risk of non-insulin-dependent diabetes mellitus . DESIGN Cohort study . SETTING In 1986 , a total of 65173 US women 40 to 65 years of age and free from diagnosed cardiovascular disease , cancer , and diabetes completed a detailed dietary question naire from which we calculated usual intake of total and specific sources of dietary fiber , dietary glycemic index , and glycemic load . MAIN OUTCOME MEASURE Non-insulin-dependent diabetes mellitus . RESULTS During 6 years of follow-up , 915 incident cases of diabetes were documented . The dietary glycemic index was positively associated with risk of diabetes after adjustment for age , body mass index , smoking , physical activity , family history of diabetes , alcohol and cereal fiber intake , and total energy intake . Comparing the highest with the lowest quintile , the relative risk ( RR ) of diabetes was 1.37 ( 95 % confidence interval [ CI ] , 1.09 - 1.71 , P trend=.005 ) . The glycemic load ( an indicator of a global dietary insulin dem and ) was also positively associated with diabetes ( RR= 1.47 ; 95 % CI , 1.16 - 1.86 , P trend=.003 ) . Cereal fiber intake was inversely associated with risk of diabetes when comparing the extreme quintiles ( RR=0.72 , 95 % CI , 0.58 - 0.90 , P trend=.001 ) . The combination of a high glycemic load and a low cereal fiber intake further increased the risk of diabetes ( RR=2.50 , 95 % CI , 1.14 - 5.51 ) when compared with a low glycemic load and high cereal fiber intake . CONCLUSIONS Our results support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of diabetes in women . Further , they suggest that grains should be consumed in a minimally refined form to reduce the incidence of diabetes BACKGROUND One in 5 American children is overweight , despite a decrease in total fat consumption . This has sparked an interest in the carbohydrate composition of diets , including the glycemic index ( GI ) . OBJECTIVE To investigate whether a low-GI meal replacement ( LMR ) produced similar metabolic , hormonal , and satiety responses in overweight adolescents as a low-GI whole-food meal ( LWM ) when compared with a moderately high-GI meal replacement ( HMR ) . METHODS R and omized , crossover study comparing LMR , HMR , and LWM in 16 ( 8 male/8 female ) adolescents during 3 separate 24-hour admissions . The meal replacements consisted of a shake and a nutrition bar . Identical test meals were provided at breakfast and lunch . Metabolic and hormonal indices were assessed between meals . Measures of participants ' perceived satiety included hunger scales and ad libitum food intake . RESULTS The incremental areas under the curve for glucose were 46 % and 43 % lower after the LMR and LWM , respectively , compared with the HMR . Insulin 's incremental area under the curve was also significantly lower after both low GI test meals ( LMR = 36 % ; LWM = 51 % ) compared with the HMR . Additional food was requested earlier after the HMR than the LMR ( 3.1 vs 3.9 hours , respectively ) , although voluntary energy intake did not differ . CONCLUSIONS Differences in insulin response between the meal replacements occurred , and prolongation of satiety after the LMR , based on time to request additional food , was observed . We speculate that the prolonged satiety associated with low GI foods may prove an effective method for reducing caloric intake and achieving long-term weight control We examined breast cancer risk in association with overall glycemic index ( GI ) , glycemic load ( GL ) , and dietary carbohydrate and sugar intake in a prospect i ve cohort of 49,613 Canadian women enrolled in the National Breast Screening Study who completed a self-administered food frequency question naire between 1980 and 1985 . Linkages to national mortality and cancer data bases yielded data on deaths and cancer incidence , with follow-up ending between 1998 and 2000 . During a mean follow-up of 16.6 years , we observed 1,461 incident breast cancer cases . GI , GL , total carbohydrate and total sugar intake were not associated with breast cancer risk in the total cohort . However , there was evidence of effect modification of the association between GI and breast cancer risk by menopausal status ( p = 0.01 ) , the hazard ratio for the highest versus the lowest quintile level of GI being 0.78 ( 95 % CI = 0.52 - 1.16 ; ptrend = 0.12 ) in premenopausal women and 1.87 ( 95 % CI = 1.18 - 2.97 ; ptrend = 0.01 ) in postmenopausal women . The associations between GI and GL were not modified by body mass index ( BMI ) or by vigorous physical activity among pre- or postmenopausal women . Similarly , the associations between GI/GL and risk in postmenopausal women were not modified by BMI , vigorous physical activity , or ever use of hormone replacement therapy ( HRT ) , although the associations were slightly stronger among those who reported no vigorous physical activity ( ptrend = 0.02 ) , among those who reported ever using HRT ( ptrend = 0.02 ) and among normal-weight women ( BMI < 25 kg/m2 ; ptrend = 0.03 ) . Our data suggest that consumption of diets with high GI values may be associated with increased risk of breast cancer among postmenopausal women , possibly more so among subgroups defined by participation in vigorous physical activity , ever use of HRT and those who are not overweight There is some evidence that plasma insulin and postload plasma glucose may be associated with risk of pancreatic cancer . Glycemic index and glycemic load are measures , which allow the carbohydrate content of individual foods to be classified according to their postpr and ial glycemic effects and hence their effects on circulating insulin levels . Therefore , we examined pancreatic cancer risk in association with glycemic index ( GI ) , glycemic load ( GL ) , and intake of dietary carbohydrate and sugar in a prospect i ve cohort of 49,613 Canadian women enrolled in the National Breast Screening Study ( NBSS ) who completed a self-administered food frequency question naire between 1980 and 1985 . Linkages to national cancer and mortality data bases yielded data on cancer incidence and deaths , with follow-up ending between 1998 and 2000 . During a mean 16.5 years of follow-up , we observed 112 incident pancreatic cancer cases . There was no association between overall glycemic index , glycemic load , total carbohydrate and total sugar intake and pancreatic cancer risk . In multivariate adjusted models , the hazard ratio ( HR ) for the highest versus lowest quartile levels of overall GI and GL were 1.43 ( 95 % confidence interval [CI]=0.56–3.65 , Ptrend=0.58 ) and 0.80 ( 95 % CI=0.45–1.41 , Ptrend=0.41 ) , respectively . Our data suggest that overall glycemic index and glycemic load , as well as total sugar and total carbohydrate intake , are not associated with pancreatic cancer risk . However , given the limited literature regarding the role of diet in the etiology of pancreatic cancer , particularly with respect to glycemic index/load , further investigation is warranted OBJECTIVE Intake of carbohydrates that provide a large glycemic response has been hypothesized to increase the risk of NIDDM , whereas dietary fiber is suspected to reduce incidence . These hypotheses have not been evaluated prospect ively . RESEARCH DESIGN AND METHODS We examined the relationship between diet and risk of NIDDM in a cohort of 42,759 men without NIDDM or cardiovascular disease , who were 40–75 years of age in 1986 . Diet was assessed at baseline by a vali date d semiquantitative food frequency question naire . During 6-years of follow-up , 523 incident cases of NIDDM were documented . RESULTS The dietary glycemic index ( an indicator of carbohydrate 's ability to raise blood glucose levels ) was positively associated with risk of NIDDM after adjustment for age , BMI , smoking , physical activity , family history of diabetes , alcohol consumption , cereal fiber , and total energy intake . Comparing the highest and lowest quintiles , the relative risk ( RR ) of NIDDM was 1.37 ( 95 % CI , 1.02–1.83 , P trend = 0.03 ) . Cereal fiber was inversely associated with risk of NIDDM ( RR = 0.70 ; 95 % CI , 0.51–0.96 , P trend = 0.007 ; for > 8.1 g/day vs. < 3.2 g/day ) . The combination of a high glycemic load and a low cereal fiber intake further increased the risk of NIDDM ( RR = 2.17 , 95 % CI , 1.04–4.54 ) when compared with a low glycemic load and high cereal fiber intake . CONCLUSIONS These findings support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of NIDDM in men . Further , they suggest that grains should be consumed in a minimally refined form to reduce the incidence of NIDDM The aim of the present cross-sectional study was to examine the agreement and disagreement between a 7 d diet diary ( 7DD ) and a self-administered machine-readable food-frequency question naire ( FFQ ) asking about diet in the previous year , and to vali date both methods with biomarkers of nutrient intake . The subjects were an age- and employment- grade -stratified r and om sub sample of London-based civil servants ( 457 men and 403 women ) , aged 39 - 61 years , who completed both a 7DD and a FFQ at phase 3 follow-up ( 1991 - 1993 ) of the Whitehall II study . Mean daily intakes of dietary energy , total fat , saturated , monounsaturated and polyunsaturated fatty acids , linoleic acid , total carbohydrate excluding fibre , sugars , starch , dietary fibre , protein , vitamin C , vitamin E ( as alpha-tocopherol equivalents ) , folate , carotenes ( as total beta-carotene activity ) , Fe , Ca , Mg , K and alcohol were measured . Serum cholesteryl ester fatty acids ( CEFA ) , plasma alpha-tocopherol and beta-carotene were also measured as biomarkers . Estimates of mean energy intake from the two methods were similar in men , and some 10 % higher according to the FFQ in women . Compared with the 7DD , the FFQ tended to overestimate plant-derived micronutrient intakes ( carotenes from FFQ v. 7DD men 2713 ( SD 1455 ) v. 2180 ( SD 1188 ) microg/d , women 3100 ( SD 1656 ) v. 2221 ( SD 1180 ) microg/d , both differences P<0.0001 ) and to underestimate fat intake . Against plasma beta-carotene/cholesterol , carotene intake was as well estimated by the FFQ as the 7DD ( Spearman rank correlations , men 0.32 v. 0.30 , women 0.27 v. 0.22 , all P < or = 0.0001 , energy-adjusted data ) . Ranking of participants by other nutrient intakes tended to be of the same order according to the two dietary methods , e.g. rank correlations for CEFA linoleic acid against FFQ and 7DD estimates respectively , men 0.38 v. 0.41 , women 0.53 v. 0.62 , all P < or = 0.0001 , energy-adjusted % fat ) . For alpha-tocopherol there were no correlations between plasma level and estimated intakes by either dietary method . Quartile agreement for energy-adjusted nutrient intakes between the two self-report methods was in the range 37 - 50 % for men and 32 - 44 % for women , and for alcohol , 57 % in both sexes . Disagreement ( misclassification into extreme quartiles of intake ) was in the range 0 - 6 % for both sexes . The dietary methods yielded similar prevalences ( about 34 % ) of low energy reporters . The two methods show satisfactory agreement , together with an expected level of systematic differences , in their estimates of nutrient intake . Against the available biomarkers , the machine-readable FFQ performed well in comparison with the manually coded 7DD in this study population . For both methods , regression-based adjustment of nutrient intake to mean dietary energy intake by gender appears on balance to be the optimal approach to data presentation and analysis , in view of the complex problem of low energy reporting The glycemic effects of diets high in refined grains and starchy foods might increase stomach cancer risk by affecting circulating glucose , insulin and insulin-like growth factor-I levels . No prospect i ve data on the role of high glycemic load and glycemic index diets on stomach cancer risk have been reported . We therefore prospect ively investigated dietary glycemic load , overall glycemic index and carbohydrate intake in relation to the incidence of stomach cancer among 61,433 women in the population -based Swedish Mammography Cohort . Diet was assessed at baseline ( 1987 - 1990 ) and again in 1997 . During 903,586 person-years of follow-up , a total of 156 incident cases of stomach cancer were ascertained . We observed no material associations of dietary glycemic load , overall glycemic index and total carbohydrate intake with the risk of stomach cancer . The multivariate hazard ratios for the highest versus the lowest quintile were 0.76 ( 95 % CI = 0.46 - 1.25 ) for glycemic load , 0.77 ( 95 % CI = 0.46 - 1.30 ) for overall glycemic index and 0.85 ( 95 % CI = 0.50 - 1.43 ) for carbohydrate intake . The associations did not vary according to body mass index . Lack of information on Helicobacter pylori infection status did not allow stratification by this potential effect modifier . Findings from this population -based prospect i ve cohort of middle-aged and elderly women did not provide evidence of a positive association between glycemic load , glycemic index and carbohydrate intake with risk of stomach cancer The aim of this study was to evaluate the reproducibility and validity of a 61-item semiquantitative food frequency question naire used in a large prospect i ve study among women . This form was administered twice to 173 participants at an interval of approximately one year ( 1980 - 1981 ) , and four one-week diet records for each subject were collected during that period . Intraclass correlation coefficients for nutrient intakes estimated by the one-week diet records ( range = 0.41 for total vitamin A without supplements to 0.79 for vitamin B6 with supplements ) were similar to those computed from the question naire ( range = 0.49 for total vitamin A without supplements to 0.71 for sucrose ) , indicating that these methods were generally comparable with respect to reproducibility . With the exception of sucrose and total carbohydrate , nutrient intakes from the diet records tended to correlate more strongly with those computed from the question naire after adjustment for total caloric intake . Correlation coefficients between the mean calorie-adjusted intakes from the four one-week diet records and those from the question naire completed after the diet records ranged from 0.36 for vitamin A without supplements to 0.75 for vitamin C with supplements . Overall , 48 % of subjects in the lowest quintile of calorie-adjusted intake computed from the diet records were also in the lowest question naire quintile , and 74 % were in the lowest one of two question naire quintiles . Similarly , 49 % of those in the highest diet record quintile were also in the highest question naire quintile , and 77 % were in the highest one or two question naire quintiles . These data indicate that a simple self-administered dietary question naire can provide useful information about individual nutrient intakes over a one-year period |
12,905 | 22,987,094 | Conclusions Of the cytokine and growth factor agents studied for oral mucositis , the evidence only supports use of palifermin in the specific population listed above . | Purpose The aim of this project was to review the literature and define clinical practice guidelines for the use of cytokines and growth factor agents for the prevention or treatment of oral mucositis induced by cancer chemotherapy or radiotherapy . | BACKGROUND The aim of this study was to evaluate the effectiveness of granulocyte-macrophage colony-stimulating factor ( GM-CSF ) mouthwashes in the prevention of severe mucositis induced by high doses of chemotherapy . PATIENTS AND METHODS Ninety consecutive patients affected by solid tumors and undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue were r and omized to receive placebo versus GM-CSF mouthwash 150 micro g/day . Patients were stratified on the basis of the conditioning treatment and the consequent different risk of severe oral mucositis . Treatment was administered from the day after the end of chemotherapy until the resolution of stomatitis and /or neutrophil recovery . RESULTS The statistical analyses were intention-to-treat and involved all patients who entered the study . The severity of stomatitis was evaluated daily by the physicians according to National Cancer Institute Common Toxicity Criteria . Both study and control groups were compared with respect to the frequency [ 30 % versus 36 % , chi(2 ) exact test , not significant ( NS ) ] and mean duration ( 4.8 + /- 4.7 versus 4.4 + /- 2.7 days , t-test , NS ) of severe stomatitis ( grade > or = 3 ) . Oral pain was evaluated daily by patients themselves by means of a 10 cm analog visual scale : the mean ( + /- st and ard error of the mean ) maximum mucositis scores were 4.8 + /- 3.5 versus 4.2 + /- 3.5 cm ( t-test , NS ) . Furthermore , 15/46 patients in the study group ( 33 % ) and 19/44 patients in the control group experienced pain requiring opioids ( chi(2 ) exact test , NS ) . CONCLUSION We did not find any evidence to indicate that prophylaxis with GM-CSF mouthwash can help to reduce the severity of mucositis in the setting of the patients we studied PURPOSE To compare granulocyte-macrophage colony-stimulating factor ( GM-CSF ) mouthwashes with sucralfate mouthwashes in the prevention of radiation-induced mucositis . METHODS AND MATERIAL S Forty patients with radically operated head- and -neck cancer were r and omly allocated to use either GM-CSF ( n = 21 ) or sucralfate ( n = 19 ) mouthwashes during postoperative radiotherapy ( RT ) . All patients received conventionally fractionated RT to a total dose of 50 - 60 Gy in 2-Gy daily fractions during 5 - 6 weeks to the primary site and regional lymphatics . A minimum of 50 % of the oral cavity and oropharyngeal mucosa was included in the clinical target volume . GM-CSF mouthwashes consisted of 37.5 microg GM-CSF and sucralfate mouthwashes of 1.0 g of sucralfate distilled in water . Both washes were used 4 times daily , beginning after the first week of RT and continued to the end of the RT course . Symptoms related to radiation mucositis and body weight , serum prealbumin level , and blood cell counts were monitored weekly . RESULTS Oral mucositis tended to be less severe in the GM-CSF group ( p = 0.072 ) . Complete ( n = 1 ) or partial ( n = 4 ) healing of mucositis occurred during the RT course in 5 patients ( 24 % ) in the GM-CSF group and in none of the patients in the sucralfate group ( p = 0.049 ) . Patients who received GM-CSF had less mucosal pain ( p = 0.058 ) and were less often prescribed opioids for pain ( p = 0.042 ) . Three patients in the sucralfate group needed hospitalization for mucositis during RT compared with none in the GM-CSF group . Four patients ( 21 % ) in the sucralfate group and none in the GM-CSF group required an interruption in the RT course ( p = 0.042 ) . No significant differences in weight , prealbumin level , or blood cell count were found between the groups , and both mouthwashes were well tolerated . CONCLUSION GM-CSF mouthwashes may be moderately more effective than sucralfate mouthwashes in preventing radiation-induced mucositis and mucositis-related pain , and their use may lead to less frequent RT course interruptions from mucositis . The present findings need to be confirmed before adopting GM-CSF mouthwashes in routine clinical use BACKGROUND Mucositis is one of the most frequent and severe side-effect of chemotherapy in childhood-cancer patients for which there is no prophylaxis available . The efficacy and feasibility of a TGF-beta(2)-enriched feeding for preventing oral and gastro-intestinal-mucositis in childhood-cancer patients were studied . PROCEDURE The study was design ed as a two-period cross-over , r and omized , double-blinded , placebo , controlled trial . Patients who had a high risk for developing mucositis and who would receive two comparable cycles of chemotherapy were eligible for the study . During one cycle of chemotherapy , TGF-beta(2)-enriched feeding was administered ; during the other , a " placebo " ( not enriched ) feeding was used . WHO toxicity scales of diarrhea , oral mucositis , fever , anal lesions and nausea/vomiting were scored daily . In addition , the incidence of occurrence of blood cultures , antibiotic therapy , and interventions or diagnostics related to mucositis were measured . RESULTS The feasibility of the study was good : 83 % of the patients completed two cycles and 86 % of the study -feeding was effectively consumed . Administration of TGF-beta(2 ) was safe as serum TGF-beta(2 ) did not increase , and renal and liver function were not affected during TGF-beta(2 ) consumption compared to normal feeding . Differences in toxicity , scored during the whole observation period and the number of days with WHO 3/4 toxicity , were not significantly different between cycles with TGF-beta(2 ) enriched and normal feeding . CONCLUSIONS TGF-beta(2 ) administration via feeding is well tolerated and safe . Although this study might have had limitations to show potential benefit of TGF-beta(2 ) , it does not provide evidence that TGF-beta(2 ) decreases the incidence or degree of mucositis induced by combination chemotherapy in childhood-cancer patients Conditioning therapy in connection with haematopoietic SCT ( HSCT ) induces a disruption of the intestinal barrier function facilitating the permeation of bacteria and endotoxin through the bowel wall with subsequent increased risk of septicaemia and a worsening of GVHD in the allogeneic setting . Palifermin ( recombinant human keratinocyte growth factor ) reduces the severity of oral mucositis with HSCT . The present trial investigates its effect on intestinal barrier function . Seventeen lymphoma patients undergoing autologous HSCT received palifermin . Intestinal permeability was assessed before the conditioning therapy and on days + 4 and + 14 . Clinical oral and gastrointestinal toxicity was prospect ively assessed in parallel . A comparison was made with matched historical study patients ( n=21 ) . Patients treated with palifermin had a significantly better preserved intestinal barrier function ( P=0.01 on day + 4 ) and were in less need of total parenteral nutrition ( P=0.005 ) as compared with controls . No significant reduction of clinical gastrointestinal or oral toxicity was observed . The intestinal barrier function , normally disrupted by the conditioning therapy , is preserved by palifermin . Whether intestinal barrier preservation protects from invasive infections , and in the allogeneic setting diminishes GVHD severity , remains to be investigated in r and omized controlled trials Oral mucositis is a frequent side effect of myeloablative chemo- and radiotherapy preceding stem cell transplantation . It causes pain , poor food intake , and is a port of entry for infection . We studied whether GM-CSF applied topically in the oral cavity can prevent or ameliorate this mucositis . In 36 consecutive patients undergoing a stem cell transplantation , we performed a double-blind placebo-controlled study of 300 µg GM-CSF in a 2 % methylcellulose gel daily versus a 2 % methylcellulose gel alone . Both were locally applied in the oral cavity . The primary end-point was mucositis as measured by the WHO toxicity scale for mucositis , oral assessment scale , and a subjective pain scale , all scored daily . The secondary end-points were need to give parenteral nutrition and morphine , incidence of fever and infections , and duration of neutropenia and hospitalization . No differences were found in the median subjective pain scores , WHO scores , and oral assessment scores between the placebo and the GM-CSF groups . In both groups , nine patients required morphine for pain control . Ten patients in the placebo group and 11 in the GM-CSF group received parenteral nutrition . Documented infections , use of broad-spectrum antibiotics , and number of days with fever were similar in the placebo and the GM-CSF groups . The duration of neutropenia below 0.5 × 109/l ( median 14.5 days in the placebo group versus 17 days in the GM-CSF group ) and the duration of hospitalization ( 28.5 versus 29 days ) was also not significantly different . We found no beneficial effect of 300 µg GM-CSF dissolved in a 2 % methylcellulose gel applied locally for chemo- and radiotherapy-induced mucositis in patients undergoing a stem cell transplantation PURPOSE Oral mucositis ( OM ) is one of the most debilitating and common side effects in patients treated with high-dose chemotherapy supported by haematopoietic stem cell transplantation ( HSCT ) . We tested the effectiveness of palifermin to avoid oral mucosal injury induced by the conditioning regimen . PATIENTS AND METHODS Twenty patients with haematological malignancies were treated with palifermin for prevention of OM during HSCT procedures . Nine patients received allogeneic haematopoietic stem cells , and in 11 autologous HSCT was performed . The control group was composed of patients who had been treated with HSCT previously , before the palifermin era . The source of graft was peripheral blood . RESULTS Among patients treated with palifermin no grade 2 - 4 OM was observed . No patient had to receive opioid analgesics or total parenteral nutrition . 30 % of the patients developed grade 1 OM of 4 - 5 days ' duration . In the control group OM was observed in all cases , with 50 % of the patients developing grade 3 - 4 OM . Median duration of OM was 10 and 12 days for auto- and allogeneic patients , respectively . In comparison with the control group , treatment with palifermin was associated with significant reduction of grade 2 - 4 OM , shorter duration of OM , less analgesics intake , and reduced number of days with antibiotic treatment . Additionally , allogeneic patients treated with palifermin had shorter time to platelet engraftment . CONCLUSION Palifermin reduces incidence , severity and duration of OM , and decreases the number of days with analgesics and antibiotics . For allogeneic patients it can shorten the time to platelet engraftment , but this observation needs further studies ATL-104 is a potent mitogen for epithelial cells of the gastrointestinal tract . In animal models , ATL-104 aids regeneration of the gastrointestinal tract after treatment with chemotherapeutic agents . The effect of ATL-104 on mucositis in patients requiring high-dose melphalan or BEAM before peripheral blood SCT ( PBSCT ) was investigated in a r and omized , placebo-controlled , double-blind , two-part study . Patients were r and omized to ATL-104 ( 50 , 100 or 150 mg ) or placebo once daily for 3 days before chemotherapy and 3 days after PBSCT . Part one of the study was a dose-escalation design ; part two was a parallel group design using all three ATL-104 doses . Patients were followed up for 28 days post-treatment . Severity of signs and symptoms were assessed and used to calculate scores for st and ard toxicity rating scales ( WHO , Western Consortium for Cancer Nursing Research ( WCCNR ) ) . Sixty-three patients were treated . Treatment with ATL-104 substantially reduced the median duration of severe oral mucositis ( WHO grade 3 or 4 ) compared with placebo ( median duration : ATL-104 groups 2 or 3 days , placebo 10.5 days ) . The effect of ATL-104 on the incidence of severe oral mucositis was inconclusive . Similar results were obtained using the WCCNR Scale . Adverse events ( AEs ) were predominantly mild or moderate in intensity . Gastrointestinal AE were most common Goals of workThe objective of this study was to evaluate the safety and tolerability of velafermin in patients at risk of developing severe oral mucositis ( OM ) from chemotherapy . Material s and methods This study was a single-center , open-label , single-dose escalation , phase I trial in patients undergoing high-dose chemotherapy ( HDCT ) and autologous peripheral blood stem cell transplant ( PBSCT ) . Velafermin was administered 24 h after stem cell infusion as a single intravenous dose infused over 15 min . Clinical safety variables were assessed and OM status scored daily for 30 days using the World Health Organization ( WHO ) grading scale . Main results Thirty patients were treated with velafermin at doses of 0.03 ( n = 10 ) , 0.1 ( n = 10 ) , 0.2 ( n = 8) , or 0.33 mg/kg ( n = 2 ) . Patients were diagnosed with multiple myeloma ( n = 16 ) , non-Hodgkin ’s lymphoma ( n = 12 ) , acute myelogenous leukemia ( n = 1 ) , or desmoplasmic round cell tumor ( n = 1 ) . Velafermin was well tolerated at doses up to 0.2 mg/kg . There were no drug-related serious adverse events . No patient discontinued because of adverse events ; however , two patients administered 0.33 mg/kg developed adverse reactions immediately after infusion of the study drug . No other patients were treated at this dose level . The most frequent ( > 35 % of patients ) treatment-emergent adverse events were diarrhea , fatigue , pyrexia , vomiting , and nausea . Most adverse events were mild or moderate and resolved the same day without sequelae . Eight ( 27 % ) patients developed WHO grade 3 or 4 OM during the study ; seven of these patients received high-dose melphalan as a conditioning regimen . Conclusion Velafermin was well tolerated by autologous PBSCT patients at doses up to 0.2 mg/kg PURPOSE To evaluate the safety of recombinant human keratinocyte growth factor ( KGF ) when administered with fluorouracil ( FU ) in patients with metastatic colorectal cancer . PATIENTS AND METHODS Patients ( N = 81 ) received KGF by intravenous ( IV ) bolus on days 1 to 3 , followed by FU 425 mg/m2/d IV bolus plus leucovorin 20 mg/m2/d IV on days 4 to 8 . KGF dose levels were 1 , 10 , 20 , 40 , 60 , and 80 microg/kg/d . A r and omized , placebo-controlled design was employed ( 2:1 r and omization of KGF to placebo ) . Oral mucositis was assessed by examination on days 1 , 4 , 8 , 15 , and 28 . In addition , patients provided daily assessment s of oral symptoms using a self-administered question naire . RESULTS Skin and oral events occurred in 13 of 18 patients ( eight patients , grade 1 ; four patients , grade 2 ; and one patient , grade 3 ) treated with 60 and 80 microg/kg of KGF and three of 11 patients treated with 40 microg/kg ( grade 1 ) . These symptoms were dose limiting in three cases ( ie , in two of 10 patients treated with 80 microg/kg and in one of eight patients treated with 60 microg/kg ) . The frequency of grade 2 to 4 mucositis was 43 % in patients treated with KGF , compared with 67 % in patients treated with placebo ( P = .06 ) . Patient self- assessment s of oral pain and clinical assessment s of mucositis showed good correlation ( Kendall 's tau = 0.75 ) . CONCLUSION KGF is generally well tolerated when administered IV at doses up to 40 microg/kg/d for 3 days before a 5-day course of FU plus leucovorin . A clinical ly meaningful biologic effect was also suggested in that patients treated with the epithelial growth factor KGF had a lower rate of grade 2 to 4 mucositis than did patients treated with placebo We wished to determine if filgrastim administration to chemotherapy/radiation therapy-naive patients receiving external-beam irradiation for head- and -neck malignancies would reduce the incidence and severity of oral/oropharyngeal mucositis . Patients were r and omized to receive subcutaneous injections of either filgrastim or placebo beginning on day 1 of radiation and continuing daily throughout treatment . Study medication was titrated to keep the neutrophil count between 10 x 10(9 ) and 30 x 10(9)/l . The left and right buccal mucosa , hard palate , and posterior pharyngeal wall were scored weekly , by a blinded evaluator using two different scales , and the most severe score per week was used in data analysis . Fourteen of a planned 54 patients were r and omized ( 8 filgrastim , 6 placebo ) , and were evaluable for a planned interim analysis . No statistically significant between-group differences were seen in mean worst scores across time using repeated measures analysis of variance ( Hickey , p = 0.231 ; WHO , p= 0.288 ) . At almost all timepoints , however , the worst mean scores were lower in patients treated with filgrastim compared with those in patients treated with placebo , and the number of severe ( i.e. , grade 3 ) mucositis scores was significantly lower in the filgrastim-treated group . Filgrastim may decrease the severity of radiation-induced oral/oropharyngeal mucositis PURPOSE This study evaluated the safety and efficacy of recombinant human intestinal trefoil factor ( rhITF ) administered as topical oral spray for prevention and treatment of chemotherapy-induced oral mucositis ( OM ) . PATIENTS AND METHODS Ninety-nine patients with colorectal cancer who had moderate to severe OM ( WHO grade > or= 2 ) in the first cycle of chemotherapy were r and omly assigned to receive either placebo , rhITF 10 mg/mL ( ie , low dose ) , or rhITF 80 mg/mL ( ie , high dose ) by oral spray ( 300 microL , eight times each day ) for 14 consecutive days in the second chemotherapy cycle . Patients were assessed on days 1 , 3 , 5 , 7 , 10 , 12 , 14 , and 21 ( + /- 2 days for the last assessment ) for safety and for OM incidence and severity . RESULTS Treatment of patients at high risk for developing OM with low- or high-dose rhITF significantly reduced the amount of incidence ( 75 % to 81 % ; low-dose rhITF P < .001 ; high-dose rhITF P = .002 ) . Frequencies of WHO grade > or= 2 OM in the placebo , low-dose rhITF , and high-dose rhITF groups were 48.5 % , 9.1 % , and 12.1 % , respectively . Assessment of the area under the curve revealed statistically significant reductions in OM severity in the rhITF-treated groups versus placebo . Only a minority of patients ( 6.1 % ) reported treatment-emergent adverse events ( TEAEs ) , all of which were mild to moderate in intensity and resolved without sequelae . The incidence of TEAEs was not significantly different among treatment groups . CONCLUSION rhITF oral spray formulation was safe and effective when used for the reduction of chemotherapy-associated OM in patients with colorectal cancer . Patients exhibited high compliance in dosing administration . Future clinical study is planned to develop this drug for use in OM management in patients with cancer Oral mucositis is a dose-limiting toxicity of intensive chemotherapy . It is caused directly by the cytotoxic effect of chemotherapeutic agents and indirectly by sustained neutropenia . Severe oral mucositis is an important predisposing factor for life-threatening septic complications during aplasia . It also reduces quality of life . At present , no effective causal prophylaxis or treatment against oral mucositis is established . We performed a prospect i ve r and omised placebo-controlled trial using topical oral r-metHuG-CSF ( filgrastim ) in high- grade lymphoma patients treated according to the B-NHL protocol , which contains high-dose methotrexate and causes severe oral mucositis ( WHO grade s I – IV ) in > 50 % of patients . Between August 1996 and July 1997 , a total of 32 chemotherapy cycles were documented in eight patients ( four male , four female ) . Mucosal erythema and ulceration were recorded . All patients assessed their oral pain and impact on swallowing daily , using a subjective scale from no to maximal discomfort ( 1–10 ) . In addition , oral mucositis was assessed according to the WHO score . Filgrastim was administered in 16 cycles as a viscous mouthrinse ( carboxymethyl- cellulose 2 % , oleum citrii ) 4 × 120 μg/day from days 10 to 16 . Sixteen cycles were given to control patients , of these 14 with placebo , and another two cycles with no treatment . Severe mucositis ( WHO grade III/IV ) was documented in 21 of 32 cycles ( 65.5 % ) . A difference of borderline significance was observed for the reduction of maximum severity of oral mucositis between G-CSF vs placebo ( P = 0.058 ) , with a reduction of WHO grade IV of 50 % ( four G-CSF vs eight control ) . The number of days in hospital was reduced significantly in the G-CSF group ( P = 0.02 ) . In conclusion , topical oral G-CSF mouthrinses may be beneficial to reduce oral mucositis The purpose of this study was to establish the safety and tolerability of recombinant transforming growth factor-beta3 ( TGF-beta3 ; CGP 46614 ) mouthwashes intended for prevention of chemotherapy-induced mucositis . Local effects were especially analyzed by objective and subjective measurements of mucositis . Secondary aims were analysis of potential systemic exposure and development of anti-TGF-beta3-antibodies . Eleven breast cancer patients received chemotherapy with 1.5 g/m2 cyclophosphamide i.v . , 80 mg/m2 epirubicin i.v . , and 1.0 g/m2 5-fluorouracil i.v . ( n = 8) or 1.6 g/m2 carboplatin i.v . , 480 mg/m2 thiotepa i.v . , and 6 g/m2 cyclophosphamide i.v . divided over 4 days ( n = 3 ) . TGF-beta3 mouthwashes ( 10 ml ; provided by Novartis , Basel , Switzerl and ) were administered for 4 days , four times a day , starting 1 day before chemotherapy . The dose was escalated in following patients from 25 microg/ml ( n = 3 ) to 50 microg/ml ( n = 3 ) and 100 microg/ml ( n = 5 ) . Clinical ly , the mucosa was scored objective ly and according to WHO criteria . The percentage of viable oral epithelial cells was determined by trypan blue dye exclusion . Morphology of cells was assessed in buccal smears . Plasma sample s were collected for determination of TGF-beta3 levels and anti-TGF-beta3-antibodies . Adverse events were recorded by the patient in a diary . Mouthwashes with TGF-beta3 were well tolerated . Three patients scored for mucositis > grade 0 ( WHO grading criteria ) . The percentage of viable oral epithelial cells in patients treated with 1.5 g/m2 cyclophosphamide i.v . , 80 mg/m2 epirubicin i.v . , and 1.0 g/m2 5-fluorouracil i.v . was stable , whereas in patients treated with 1.6 g/m2 carboplatin i.v . , 480 mg/m2 thiotepa i.v . , and 6 g/m2 cyclophosphamide i.v . divided over 4 days , an increase was observed . The morphology of buccal cells showed a transient shift from mature to immature cells in the first week . Neither systemic absorption of TGF-beta3 nor development of TGF-beta3-antibodies was observed . TGF-beta3 mouthwashes were well tolerated and deserve further study in preventing chemotherapy-induced mucositis BACKGROUND Oral mucositis is a complication of intensive chemotherapy and radiotherapy with no effective treatment . We tested the ability of palifermin ( recombinant human keratinocyte growth factor ) to decrease oral mucosal injury induced by cytotoxic therapy . METHODS This double-blind study compared the effect of palifermin with that of a placebo on the development of oral mucositis in 212 patients with hematologic cancers ; 106 patients received palifermin ( 60 microg per kilogram of body weight per day ) and 106 received a placebo intravenously for three consecutive days immediately before the initiation of conditioning therapy ( fractionated total-body irradiation plus high-dose chemotherapy ) and after autologous hematopoietic stem-cell transplantation . Oral mucositis was evaluated daily for 28 days after transplantation . RESULTS The incidence of oral mucositis of World Health Organization ( WHO ) grade 3 or 4 was 63 percent in the palifermin group and 98 percent in the placebo group ( P<0.001 ) . Among patients with this degree of mucositis , the median duration of mucositis was 6 days ( range , 1 to 22 ) in the palifermin group and 9 days ( range , 1 to 27 ) in the placebo group . Among all patients , regardless of the occurrence of mucositis , the median duration of oral mucositis of WHO grade 3 or 4 was 3 days ( range , 0 to 22 ) in the palifermin group and 9 days ( range , 0 to 27 ) in the placebo group ( P<0.001 ) . As compared with placebo , palifermin was associated with significant reductions in the incidence of grade 4 oral mucositis ( 20 percent vs. 62 percent , P<0.001 ) , patient-reported soreness of the mouth and throat ( area-under-the-curve score , 29.0 [ range , 0 to 98 ] vs. 46.8 [ range , 0 to 110 ] ; P<0.001 ) , the use of opioid analgesics ( median , 212 mg of morphine equivalents [ range , 0 to 9418 ] vs. 535 mg of morphine equivalents [ range , 0 to 9418 ] , P<0.001 ) , and the incidence of use of total parenteral nutrition ( 31 percent vs. 55 percent , P<0.001 ) . Adverse events , mainly rash , pruritus , erythema , mouth and tongue disorders , and taste alteration , were mild to moderate in severity and were transient . CONCLUSIONS Palifermin reduced the duration and severity of oral mucositis after intensive chemotherapy and radiotherapy for hematologic cancers Palifermin , a recombinant human keratinocyte growth factor , was tested for potential benefits on acute graft-versus-host disease ( GVHD ) and hematopoietic recovery in allogeneic hematopoietic stem cell transplantation ( HSCT ) recipients . This r and omized , double-blind , placebo-controlled , dose-escalation study assessed the safety and tolerability of palifermin ( n = 69 ) as compared with placebo ( n = 31 ) in patients conditioned with cyclophosphamide and fractionated total-body irradiation ( Cy/TBI ) or busulfan and cyclophosphamide ( Bu/Cy ) and given methotrexate along with a calcineurin inhibitor ( cyclosporine A , tacrolimus ) for GVHD prophylaxis . All patients received 3 doses before conditioning and either 3 ( cohort 1 ) , 6 ( cohort 2 ) , or 9 ( cohort 3 ) doses after HSCT . Palifermin doses were 40 mug/kg per day ( cohort 1 only ) or 60 mug/kg per day ( all cohorts ) . Six patients ( placebo = 2 , palifermin = 4 ) experienced a total of 11 dose-limiting toxicities ( most often skin , respiratory , or oral mucositis ) . The most common adverse events included edema , infection , skin pain , or rash . Times to neutrophil and platelet engraftment were similar . No significant differences in acute GVHD incidence or severity , survival , or day 100 relapse rates were observed between groups . Palifermin was associated with reduced incidence and mean severity of mucositis in patients conditioned with Cy/TBI but not Bu/Cy . We conclude that palifermin was generally safe in allogeneic HSCTs but had no significant effect on engraftment , acute GVHD , or survival in this trial In this multicenter study , we assessed the use of palifermin ( recombinant human – keratinocyte growth factor 1 ) in the prevention of oral mucositis ( OM ) and acute GvHD ( aGvHD ) induced by a hematopoietic stem cell transplant ( HSCT ) . Fifty-three patients with hematological diseases received three doses of palifermin ( 60 μg/kg once daily i.v . ) pre- and post-conditioning regimens ( total six doses ) . A retrospective control group of 53 transplant patients received no palifermin . There was a significant reduction in the incidence of OM of WHO ( World Health Organization ) grade s 1–4 ( 58 vs 94 % , P<0.001 ) , 3–4 ( 13 vs 43 % , P<0.001 ) and the median duration of OM ( 4 vs 9 days , P<0.001 ) in the palifermin group compared to the control group . The incidence of analgesics ( 32 vs 75.5 % , P<0.001 ) , opioid analgesics ( 24 vs 64 % , P<0.001 ) and total parenteral nutrition ( 11 vs 45 % , P<0.001 ) was also significantly reduced . The analysis of distribution of affected organs revealed that aGvHD was less prevalent in the palifermin group ( P=0.036 ) . There was no significant difference in the onset of any OM after HSCT , time to engraftment and length of hospitalization between groups . The drug was generally well tolerated and safe . Our results suggest that the use of palifermin reduces OM and probably aGvHD after HSCT , but a r and omized trial is needed We previously conducted a r and omized , double-blind , placebo-controlled study conducted from 2000 to 2003 of palifermin , a recombinant human keratinocyte growth factor , dosed from 240 microg/kg to 720 microg/kg , in 100 allogeneic hematopoietic stem cell transplantation ( HCT ) recipients . Treatment with palifermin showed beneficial effects on mucositis , but no significant effect on engraftment , acute graft-versus-host disease ( GVHD ) , or early survival . In addition to the effect of palifermin on mucosa , other pleotrophic effects , including more rapid immune reconstitution , have been seen in experimental transplant models . Therefore , we investigated whether with longer follow-up we could detect additional differences between the palifermin-treated and placebo cohorts . We found no differences in CMV or invasive fungal infections , chronic GVHD , or long-term survival between cohorts . We conclude that the benefits of palifermin appear primarily to be limited to ameliorating mucotoxicity when given to allogeneic HCT recipients PURPOSE Oral mucositis ( OM ) is a debilitating toxicity of chemoradiotherapy for head and neck cancer ( HNC ) . This r and omized , placebo-controlled , double-blind study evaluated the efficacy and safety of palifermin to reduce OM associated with definitive chemoradiotherapy for locally advanced HNC . PATIENTS AND METHODS Patients receiving conventionally fractionated radiotherapy ( 2.0 Gy/d , 5 days/wk to 70 Gy ) with cisplatin ( 100 mg/m(2 ) on days 1 , 22 , and 43 ) received palifermin ( 180 μg/kg ) or placebo before starting chemoradiotherapy and then once weekly for 7 weeks . The primary end point was the incidence of severe , observable , and functional OM ( WHO grade 3 to 4 ) . RESULTS The palifermin ( n = 94 ) and placebo ( n = 94 ) arms were well balanced . The incidence of severe OM was significantly lower for palifermin than for placebo ( 54 % v 69 % ; P = .041 ) . In the palifermin arm , median time to severe OM was delayed ( 47 v 35 days ) , median duration of severe OM was shortened ( 5 v 26 days ) , and the incidence of xerostomia grade ≥ 2 was lower ( 67 % v 80 % ) , favoring palifermin ; however , the differences were not significant after multiplicity adjustment . Opioid analgesic use , average mouth and throat soreness scores , and chemoradiotherapy compliance were not significantly different between treatment arms . Adverse events were similar between arms ( 98 % , palifermin ; 93 % , placebo ) . The most common study drug-related adverse events were rash , flushing , and dysgeusia . After median follow-up of 25.8 months , overall survival and progression-free survival were similar between treatment arms . CONCLUSION Although palifermin reduced severe functional OM , its role in the management of locally advanced HNC during chemoradiotherapy remains to be eluci date The authors had previously reported preliminary results of a treatment regimen of concurrent hyperfractionated radiation therapy and chemotherapy in patients with locally advanced head and neck carcinoma that demonstrated both feasibility and high local control . In an attempt to reduce acute mucosal and hematologic toxicity , granulocyte‐colony stimulating factor ( G‐CSF ) was added during the second phase of this study The combination of radiation and chemotherapy administered for patients undergoing therapy for advanced head and neck neoplasms leads to a significant rise in toxic side-effects . Oral mucositis remains one of the most distressing factors leading to pain , impairment of oral nutrition , local and systemic infection and often cessation of the oncological treatment . The local and systemic administration of recombinant growth factors has revealed a potential benefit in the treatment of oral mucositis . Clinical data concerning the topical use of granulocyte-macrophage colony-stimulating-factor ( GM-CSF ) in the prevention and therapy of mucositis in patients undergoing radiochemotherapy for advanced cancer of the head and neck are presented in this paper . A prospect i ve , r and omised , open parallel-grouped , single centre study at a university hospital was performed . 35 patients with stage III and IV carcinomas of the head and neck were included . Statistical analysis concerning the degree of oral mucositis , the perception of pain , the incidence of secondary infections and the change in haematological parameters revealed no superiority of GM-CSF in comparison to conventional mouthwash between the two groups of patients . As a result , and faced with the tremendous costs of the regular use of a recombinant cytokine , we ended the clinical trial after 35 patients . The topical administration of GM-CSF to treat oral mucositis as a result of radiochemotherapy in patients suffering from head and neck cancer can not be recommended Palifermin , a recombinant human keratinocyte growth factor , is commonly given to prevent mucositis following autologous transplantation . In the allogeneic hematopoietic stem cell transplant ( allo-HSCT ) setting , safety and efficacy data are limited . We conducted a retrospective study in 251 patients undergoing allo-HSCT , 154 of whom received peritransplant palifermin . In all patients , palifermin significantly decreased the mean number of days of total parenteral nutrition ( TPN , 13 vs 16 days , P=0.006 ) and patient-controlled analgesia ( PCA , 6 vs 10 days , P=0.023 ) , as well as the length of initial hospital stay ( LOS , 32 vs 37 days , P=0.014 ) . However , the effect of palifermin was only significant in patients who received a TBI- but not BU-based chemotherapy conditioning regimen . In TBI recipients , palifermin decreased the mean number of days of TPN ( 13 vs 17 days , P<0.001 ) and PCA ( 7 vs 12 days , P=0.033 ) , and the length of stay ( 32 vs 38 days , P=0.001 ) . Palifermin did not affect GVHD , graft failure or relapse . Therefore , in the largest analysis with this patient population to date , we demonstrate that palifermin is safe in allo-HSCT patients , decreases TPN and PCA use and decreases LOS following TBI-based but not chemotherapy-based allo-HSCT In this study , the ability of granulocyte colony-stimulating factor ( G-CSF ) to treat or prevent chemotherapy-induced oral mucositis in patients with advanced breast cancer was evaluated . A total of 14 patients who received intra-arterial ( i.a . ) adriamycin ( ADM ) preoperatively were divided into two groups according to whether or not G-CSF was given . Thus , group A ( n=7 ) was given G-CSF and group B ( n=7 ) was not . G-CSF therapy reduced both the incidence and duration of ADM-induced oral mucositis , and a positive correlation was also seen between the incidence of mucositis and ADM-induced leukopenia ( < 2,000/mm3 ) . Group A was further divided into two subgroups according to whether G-CSF was given after or before the leukopenia had dropped below 2,000/mm3 : group A-1 ( n=3 ) and group A-2 ( n=4 ) , respectively . ADM-induced mucositis was observed in two of the three patients in group A-1 , but in none of the four patients in group A-2 . These results strongly support the idea that G-CSF can effectively treat and prevent ADM-induced oral mucositis PURPOSE To determine whether granulocyte colony-stimulating factor ( G-CSF ; lenograstim ) decreases the incidence of febrile neutropenia after induction courses in treatment of childhood non-Hodgkin 's lymphoma ( NHL ) . PATIENTS AND METHODS Patients were r and omized to receive ( G-CSF+ ) or not receive ( G-CSF- ) prophylactic G-CSF , 5 microg/kg/d , from day 7 until an absolute neutrophil count > or = 500/microL was sustained over 48 hours , after two consecutive induction courses of cyclophosphamide 1.5 or 3 g/m(2 ) , vincristine 2 mg/m(2 ) , prednisone 60 mg/m(2)/d x 5 , doxorubicin 60 mg/m(2 ) , high-dose methotrexate 3 or 8 g/m(2 ) , and intrathecal injections ( COPAD[M ] ) on protocol s LMB89 , LMT89 , and HM91 of the French Society of Pediatric Oncology . RESULTS One hundred forty-eight patients were assessable , 75 G-CSF+ and 73 G-CSF- . Although duration of neutropenia less than 500/microL was 3 days shorter in G-CSF+ patients ( P = 10(-4 ) ) , incidence of febrile neutropenia ( 89 % v. 93 % in the first course , 88 % v. 88 % in the second course ) , duration s of hospitalization and antimicrobial therapy , percentages of infections , mucositis , and transfusions were not significantly different . Although the percentage of G-CSF+ patients commencing the following course on day 21 was significantly higher ( 84 % v 68 % after the first and 57 % v. 38 % after the second course ; P < .05 ) , the median delay between the two courses was only 1 day less in G-CSF+ patients ( median delay after first COPAD(M ) , 19 v. 20 days , P = .01 ; after second , 21 v. 22 days , P = not significant ) . Remission and survival rates were similar in both arms . CONCLUSION This study demonstrates that G-CSF did not decrease treatment-related morbidity , nor increase the dose-intensity in children undergoing COPAD(M ) induction chemotherapy for NHL To evaluate the ability of granulocyte-stimulating factor to decrease mucositis during postoperative radiotherapy for stage II – IV squamous head and neck cancer in a r and omized , double-blind , placebo-controlled trial . METHODS After undergoing complete resection , patients were r and omized to receive granulocyte-colony stimulating factor or placebo by daily subcutaneous injection during radiotherapy ( 63 Gy , 1.8 Gy/day ) . Patients undergoing prior radiotherapy or chemotherapy were excluded from the study . The primary outcome was the need for percutaneous endoscopic gas-trostomy placement . Severity of mucositis was a secondary outcome . RESULTS Forty-one patients were enrolled ( 132 planned ) . The study closed after slow accrual . Patient characteristics were as follows ( granulocyte-colony stimulating factor vs placebo ) : median age , 59 versus 54 years ; pT4 , 16 % versus 23 % ; pN2/3 , 68 % versus 59 % ; stage IV , 79 % versus 68 % . Forty patients were evaluable for planned outcomes . Patients in the granulocyte-colony stimulating factor arm showed trends toward lower rates of percutaneous endoscopic gastrostomy placement ( 0 % vs 14 % , P= 0.2 ) and severity of mucositis ( P = 0.13 ) , and had shorter mean radiotherapy duration ( 48.4 ± 4.32 days vs 51.6 ± 1.84 days , P = 0.005 ) . Overall survival was significantly greater in the granulocyte-colony stimulating factor arm ( hazard ratio , 0.37 ; P= 0.037 ) . DISCUSSION Granulocyte-colony stimulating factor during radiotherapy was feasible and led to significantly shorter radiotherapy duration and trends toward less percutaneous endoscopic gastrostomy placement and mucositis . The unanticipated improvement in survival outcomes warrants further hypothesis-driven investigation and validation Goal of workThe aim of this study was to compare palifermin , a recombinant form of human keratinocyte growth factor , with st and ard treatment on outcomes in patients receiving a high dose of chemotherapy conditioning regimen , undergoing hematopoietic stem cell transplantation ( HSCT ) . Material s and methods Over a 1-year period , a series of 59 patients were included : 32 patients ( palifermin ) were compared with 27 patients ( st and ard treatment ) . Outcomes assessed at day 8 posttransplantation were mucositis , swallowing , nutrition impact symptoms , dietary intake , time to engraftment , length of stay , infection , and cumulative dose and duration of narcotic administration . Main results There was a significant reduction in the incidence of severe oral mucositis ( 13 vs 48 % , p=0.003 ) , swallowing problems ( p=0.044 ) , number of nutrition impact symptoms experienced ( 4.9 vs 6.0 , p=0.003 ) , and length of stay ( 14 vs 18 days , p=0.026 ) in the palifermin group compared to st and ard care . There was no significant difference in infection , dietary intake , time to engraftment or cumulative dose and duration of narcotic administration between groups . Conclusions Beneficial outcomes were observed from the use of palifermin in patients undergoing HSCT after a high dose of chemotherapy conditioning regimen . A r and omized clinical trial is needed to confirm these results Goals of workthe aim of this paper was to review the initial use of Palifermin(rHu-KGF1 ) in a single institution , for the prevention of oral mucositis in high-dose chemotherapy and stem cell transplantation . Methods the case records of the first five patients treated with Palifermin at the Royal Adelaide Hospital Cancer Centre were review ed , and incidence , severity and duration of the oral mucositis were recorded , as well as demographics and toxicities . Results two of the five patients developed grade 4 mucositis , and the remaining three patients developed grade 2 mucositis . Palifemin was well tolerated with only one patient developing a rash . Conclusions the severity of oral mucositis was less than would be expected in these patients without anti-mucositis therapy . Palifermin was well tolerated . Obviously this single institution report is from a very small cohort of patients , but it is encouraging for the ease of use of this drug in the future A double-blind clinical trial was performed to study the effect of epidermal growth factor ( EGF ) mouthwash on the healing and recurrence of oral ulceration in 12 patients undergoing cancer chemotherapy . The oral distribution of cytotoxic-induced ulcers corresponded to the salivary gutters . There was no difference in the rate of healing of established ulcers between the experimental and placebo groups . However , there was a small delay in the onset and severity of recurrent ulceration . It was concluded that EGF mouthwash does not accelerate ulcer healing , but it may have the potential to protect the oral epithelium from cytotoxic damage We investigated whether daily oral washings with recombinant human granulocyte – macrophage colony-stimulating factor ( rhGM-CSF ) solution improved grade III – IV oropharyngeal mucositis ( OM ) in patients with hematological malignancies undergoing stem cell transplantation . Forty-one consecutive patients ( 21 males and 20 females , median age ( range ) 44 ( 16–69 ) years ) were prospect ively r and omized to perform daily mouth-washes with either a 400 μg rhGM- CSF ( Molgramostin , Schering-Plough ) solution ( group A , n = 18 ) or with a saline solution ( group B , n = 23 ) . Primary end-points were the intensity of OM , night rest quality and characteristics of food intake . Secondary end-points were need for and duration of parenteral nutrition , oral and intravenous analgesic requirements , incidence of viral or fungal oral infections and development of neutropenic fever . No differences were found between the placebo and rhGM-CSF-treated groups regarding overall duration of OM , maximum grade , reduction in at least one grade of OM ( nine patients ( 56 % ) in group A vs 13 patients ( 68 % ) in group B ) , reduction of spontaneous or swallowing-induced pain , improvement in oral food intake , use of parenteral nutrition or use of systemic analgesics . In conclusion , mouth-washings with a 400 μg of rhGM-CSF solution do not improve severe OM in hematological patients undergoing stem cell transplantation Transforming growth factor (TGF)-&bgr;3 has been hypothesized to prevent or alleviate oral mucositis ( OM ) in cancer patients receiving high-dose chemotherapy ( CT ) . Two double-blind , placebo-controlled , multicenter , phase II studies of TGF-&bgr;3 were initiated in the United States , Europe , and Argentina in patients with lymphomas or solid tumors who were receiving highly stomatotoxic CT regimens . Patients were to apply 10-mL mouthwash applications of TGF-&bgr;3 ( 25 & mgr;g/mL ) or placebo four times daily ( or twice daily ) 1 day before and all days during CT . The patients were subsequently evaluated for OM incidence , severity , and duration using National Institute of Cancer Common Toxicity Criteria ( NCI-CTC ) criteria and an objective scoring system ( 1 ) . After the start of the trials , negative results from new pre clinical studies suggesting suboptimal formulation and /or dosing led to an interim analysis of the ongoing clinical trials . One hundred fifty-two patients from the combined studies were included in the interim analysis , with 116 patients on the TGF-&bgr;3 four times daily and placebo arms . Most ( 72 % ) patients had breast cancer , 22 % had lymphomas , and 6 % had other solid tumors . Although 98 % ( 149 of 152 ) of patients experienced adverse events , only 14 % ( 22 of 152 ) experienced events that were judged as possibly or probably related to the study drug ( primarily gastrointestinal symptoms ) . No clinical ly relevant differences were seen between the treatment and placebo arms regarding safety , nor was there evidence for systemic absorption of TGF-&bgr;3 . Finally , there was no advantage of TGF-&bgr;3 treatment regarding the incidence ( TGF-&bgr;3 four times daily versus placebo [ 46 % versus 47 % ] ) , onset , or duration of NCI-CTC grade 3 or 4 OM . For this dose , formulation , regimen , and patient population , TGF-&bgr;3 was not effective in the prevention or alleviation of CT-induced OM We evaluated the efficacy of topically applied human recombinant epidermal growth factor ( rhEGF ) for the treatment of oral mucositis induced by radiotherapy ( RT ) , with or without chemotherapy , in patients with head and neck cancer PURPOSE Radiochemotherapy of head and neck cancer causes severe mucositis in most patients . We investigated whether palifermin reduces this debilitating sequela . METHODS We conducted a multicenter , double-blind , r and omized , placebo-controlled trial in 186 patients with stages II to IVB carcinoma of the oral cavity , oropharynx , hypopharynx , or larynx . Patients received 60 or 66 Gy after complete ( R0 ) or incomplete resection ( R1 ) , respectively , at 2 Gy/fraction and five fractions per week . Cisplatin 100 mg/m(2 ) was administered on days 1 and 22 ( and on day 43 with R1 ) . Patients were r and omly assigned to receive weekly palifermin 120 μg/kg or placebo from 3 days before and continuing throughout radiochemotherapy . Trained evaluators performed oral assessment s twice weekly . The primary end point was the incidence of severe oral mucositis ( WHO grade s 3 to 4 ) . Overall survival and time to locoregional progression were also assessed . Analysis was by intention to treat . RESULTS Severe oral mucositis was seen in 47 ( 51 % ) of 92 patients administered palifermin and 63 ( 67 % ) of 94 administered placebo ( P = .027 ) . Palifermin decreased the duration ( median , 4.5 v 22.0 days ) and prolonged the time to develop ( median , 45 v 32 days ) severe mucositis . Neither patient-reported mouth and throat soreness scores nor treatment breaks differed between treatment arms . After median follow-up of 32.8 months , 23 deaths ( 25 % ) had occurred in both treatment arms , and disease had recurred in 25 ( 27 % ) and 22 ( 24 % ) of palifermin- and placebo-treated patients , respectively . CONCLUSION Palifermin reduced the occurrence of severe oral mucositis in patients with head and neck cancer undergoing postoperative radiochemotherapy . Additional clinical exploration of palifermin with postoperative radiochemotherapy would be useful PURPOSE To evaluate prospect ively the efficacy of granulocyte-macrophage colony-stimulating factor ( GM-CSF ) in the reduction of chemotherapy-induced oral mucositis . PATIENTS AND METHODS Twenty patients with stage IV squamous cell carcinoma of head and neck were studied . Two-cycles ( periods ) of identical doses of cisplatin , fluorouracil ( 5-FU ) , and leucovorin ( PFL ) chemotherapy with cisplatin 20 mg/m2/d , 5-FU 800 mg/m2/d , leucovorin 90 mg/m2/d by 96-hour continuous intravenous infusion every 3 weeks were given to each patient . After PFL chemotherapy , GM-CSF 4 micrograms/kg subcutaneously from days 5 to 14 or no therapy was given by a r and omized self-controlled crossover study design . Oral mucositis was grade d with modified Radiation Therapy Oncology Group criteria . RESULTS In the first cycle of PFL chemotherapy , GM-CSF significantly reduced the incidence , mean duration , and mean area under the curve ( AUC ) of severe oral gross mucositis ( grade > or = 3 ) compared with no therapy . These beneficial effects continued into the second cycle of PFL chemotherapy after crossover to no GM-CSF . The incidence of severe mucositis was reduced when GM-CSF was given in the second cycle of PFL . Analysis of variance indicated significant direct GM-CSF treatment effects on the mean AUC of gross/functional scores and duration of moderate gross mucositis ( grade > or = 2 ) over both periods . There was a significant period effect in favor of giving GM-CSF in the first cycle of chemotherapy . CONCLUSION GM-CSF can significantly reduce the severity and duration of chemotherapy-induced oral mucositis after PFL chemotherapy Objective : To test the activity of subcutaneous granulocyte-macrophage colony-stimulating factor ( GM-CSF ) administration in patients with colorectal cancer treated with adjuvant 5-fluorouracil ( 5-FU ) plus leucovorin ( LV ) and suffering from mucositis . Methods : Thirty-one patients treated with adjuvant 5-FU 370 mg/m2 and LV 100 mg/m2 for 5 days every 4 weeks and reporting grade ≧2 mucositis participated in the study . Subcutaneous GM-CSF 4 µg/kg/day from days 6 to 10 was administered without chemotherapy dose reductions in the cycle that followed the cycle during which mucositis was reported . The disappearance of mucositis or a decrease by ≧1 grade was recorded as a therapeutic success . Baseline toxicity was : grade 2 stomatitis in 12 patients and grade 3 in 9 ; grade 4 , 3 and 2 diarrhoea in 1 , 4 and 8 patients , respectively . Results : Seventy-seven GM-CSF cycles were administered . A success was achieved in 20 ( 64.5 % ) patients . The efficacy was assessable in 5 ( 16.1 % ) patients with grade 2 and in 8 ( 25.8 % ) with grade 3 stomatitis , respectively , as well as in 1 ( 3.2 % ) and 5 ( 16.1 % ) patients with grade 3 and 2 diarrhoea , respectively . Success ( 3.2 % ) was reported in 2 patients suffering from both grade 2 stomatitis and diarrhoea . In 7 ( 22.5 % ) patients there was no evidence of efficacy . In 4 ( 12.9 % ) patients the treatment was stopped after the first administration of GM-CSF due to a grade 2 allergic reaction . Conclusions : The subcutaneous administration of GM-CSF relieved patients from symptoms of 5-FU/LV-induced mucositis with acceptable side effects permitting the maintenance of full-dose chemotherapy This single arm , open labeled , non r and omized study was aim ed to evaluate the toxicity of 3 cycles of MVAC ( methotrexate , vinblastine , doxorubicin and cisplatin ) with rhG-CSF ( 5 micrograms/kg/day from day 3 to day 14 ) , on 14 patients with previously untreated infiltrating bladder carcinoma , 42 cycles were administered . Chemotherapy toxicity was very low , with 7 % of neutropenia grade 3 or 4.4 % of thrombocytopenia grade 2 , no mucositis above grade 2 and no nadir sepsis . Bone pain related to rhG-CSF occurred in 14 % of cycles . 88 % of the cycles were given at full dose without any delay and mean relative dose intensity was 96.4 % ( RDI was 100 % for 9 patients ) . One patient achieved a complete pathological response ( cystectomy : 1 ) and 6 clinical responses with negative transurethral resection . Addition of rhG-CSF to MVAC chemotherapy allows a high dose intensity of MVAC with very low toxicity over 3 cycles . This association should be compared to st and ard MVAC or intensified regimens to evaluate efficacy , toxicity , and cost effectiveness Abstract Background . Previous studies suggested granulocyte-macrophage-colony stimulating factor ( GM-CSF ) might be beneficial for radiotherapy-induced mucositis . This trial examined the efficacy of GM-CSF in reducing mucositis of the oral cavity and /or oropharynx compared with conventional treatment . Methods . Mucositis , documented by a five- grade scale , was defined in patients with tumors of the headneck . Centers were allowed to use their own preferred fractionation regimen . R and omization to treatment was decided before radiotherapy . Treatment with GM-CSF 4 µg/kg/d subcutaneous , started when patients displayed a mucositis score ≥ 1.5 . Results . Ninety-two patients entered the study according to intention-to-treat principle . Twenty did not reach a mucositis index of 1.5 . Sixty-one patients were included in the statistical analysis . Forty-five percent of the patients r and omized to receive GM-CSF had a significant reduction of the mucositis more than one grade compared to 9 % of the conventional treated . Conclusions . In severe mucositis , GM-CSF is more effective than conventional treatment Interleukin-11 ( IL-11 ) decreases cytokine release and increases survival in murine BMT models . In these systems , it reduces gut permeability , partially polarizes T cells to a Th2 phenotype , down-regulates IL-12 , prevents mucositis , and accelerates recovery of oral and bowel mucosa . We conducted a r and omized double-blind pilot study of rhIL-11 administered with cyclosporine/MTX prophylaxis after cytoxan/TBI conditioning and allogeneic stem cell transplantation for hematologic malignancies . Patients received rhIL-11 , 50 μg/kg subcutaneously daily or placebo in a 3:1 ratio . Treatment was administered prior to the start of conditioning and continued up to 21 days . The study was design ed to assess safety with stopping rules for cardiac arrhythmias and mortality . Although projected to accrue 20 patients , only 13 patients ( 10 IL-11 , three placebo ) were enrolled because the early stopping rule for mortality was triggered . Of 10 evaluable patients who received IL-11 , four died by day 40 and one died on day 85 . Deaths were attributable to transplant-related toxicity . One of three placebo recipients died of suicide , the other two are alive . Patients receiving IL-11 had severe fluid retention and early mortality , making it impossible to determine whether IL-11 given in this schedule can reduce the rate of GVHD . Grade B – D acute GVHD occurred in two of eight evaluable patients on IL-11 and one of three patients on placebo . The primary adverse events of the study were severe fluid retention resistant to diuresis ( average weight gain 9 ± 4 % ) and multiorgan failure in five of 10 evaluable patients . The use of IL-11 as GVHD prophylaxis in allogeneic transplantation can not be recommended as administered in this trial . Bone Marrow Transplantation ( 2002 ) 29 , 373–377 . Acute mucositis is dose-limiting in many accelerated radiotherapy schedules for head and neck cancer . Cytokines may be one means of reducing the severity of mucositis . A study was design ed to assess the effect of subcutaneous molgramostin ( granulocyte-macrophage colony stimulating factor ; GM-CSF ) injections on acute radiation morbidity in patients undergoing accelerated radiotherapy for laryngeal cancer . A prospect i ve , r and omized , observer-blind , controlled trial was conducted in 29 patients who were to receive radical radiotherapy over 3 weeks for early stage laryngeal cancer . Patients were r and omized to receive 150 microg ( approximately 2 microg kg(-1 ) ) GM-CSF subcutaneously once daily for 14 days after the second week of radiotherapy , or no GM-CSF . Patients were assessed weekly for grade of mucositis , skin reactions and related parameters . The severity of mucositis was reduced in the GM-CSF arm ( p<0.05 ) . No other end-points reached statistical significance . Two patients failed to complete their courses of GM-CSF . Three developed influenza type symptoms and in one an allergic reaction was noted . There was no difference in tumour control rates . Subcutaneous GM-CSF reduced the severity of mucositis in patients undergoing accelerated radiotherapy . Injections were well tolerated . Further studies of cytokines are warranted , to assess the feasibility of increasing the total doses of accelerated radiotherapy given , with the aim of improving tumour cure rates PURPOSE To compare subcutaneously given molgramostim ( GM-CSF ) and sucralfate mouth washings to sucralfate mouth washings in prevention of radiation-induced mucositis . METHODS AND MATERIAL S Forty head and neck cancer patients were r and omly assigned to use either GM-CSF and sucralfate ( n = 20 ) or sucralfate alone ( n = 20 ) during radiotherapy . Sucralfate was used as 1.0 g mouth washing 6 times daily after the first 10 Gy of radiotherapy , and 150 - 300 microg GM-CSF was given subcutaneously . The grade of radiation mucositis and blood cell counts were monitored weekly . Salivary lactoferrin was measured as a surrogate marker for oral mucositis . RESULTS We found no significant difference between the molgramostim and the control groups in the oral mucositis grade , oral pain , use of analgesic drugs , weight loss , or survival . The median maximum neutrophil counts ( median , 9.2 x 10(9)/L vs. 5.9 x 10(9)/L , p = 0.0005 ) , eosinophil counts ( median , 1.3 x 10(9)/L vs. 0.2 x 10(9)/L , p = 0.0004 ) , and salivary lactoferrin concentrations were higher in patients who received GM-CSF . The most common toxicities in the GM-CSF plus sucralfate group were skin reactions at the GM-CSF injection site ( 65 % ) , fever ( 30 % ) , bone pain ( 25 % ) , and nausea ( 15 % ) , whereas the toxicity of sucralfate given alone was minimal . CONCLUSION We found no evidence indicating that subcutaneously given GM-CSF reduces the severity of radiation-induced mucositis BACKGROUND Mucositis is a frequent side-effect of radiotherapy which often causes interruption of therapy and consequently decreases the probability of remission or cure , rhGM-CSF may ameliorate symptoms of mucositis by increasing the immune response via macrophage activation and stimulation of secondary cytokines . PATIENTS AND METHODS 32 patients with locally advanced head and neck cancer were treated with adjuvant local radiotherapy after surgery ( 60 Gy in 30 dose fractions ) . In a pilot study , 16 patients received rhGM-CSF for five days , starting after a radiation dose of 20 Gy . These patients were compared retrospectively with a control group of 16 matching patients . Patients were assessed according to the Oral Assessment Guide ( OAG ) , the Composite Mucositis Score ( CMS ) and the Common Toxicity Criteria ( CTC ) for severity of mucositis and pain . RESULTS When compared with controls , patients on rhGM-CSF treatment showed decreased OAG , CMS and CTC scores . During the following irradiation courses mucositis was less severe in patients previously treated with rhGM-CSF . With regard to pain relief , rhGM-CSF-treated patients demonstrated a statistically significant improvement ( p = 0.011 ) , compared with controls . CONCLUSION rhGM-CSF affected the severity of oral mucositis and reduced the related pain . As rhGM-CSF was well tolerated , this effect will be further investigated in prospect i ve , controlled study Purpose : To evaluate the safety of repifermin ( keratinocyte growth factor-2 ) administered before and after autologous hematopoietic stem cell transplantation ( auto-HSCT ) . A preliminary analysis of the ability of keratinocyte growth factor-2 to prevent mucositis was also done . Experimental Design : Forty-two patients received intravenous repifermin ( 25 μg/kg or 50 μg/kg ) or placebo for 3 days before their auto-HSCT conditioning regimen and for up to 10 days after auto-HSCT . Within each dose level , 14 patients were r and omized to repifermin and 7 patients to placebo . Clinical evaluations of mucositis were scheduled before auto-HSCT conditioning regimen , on the day of transplant , and three times per week until mucositis resolved . Results : In general , the incidence of adverse events was similar for patients treated with repifermin and placebo . No clinical ly meaningful differences were noted among treatment groups for clinical laboratory variables . Treatment groups experienced similar time to engraftment . The frequency of Grade 2 to 4 mucositis was 100 % for patients in the placebo group , 64 % for patients in the 25 μg/kg group ( P = 0.041 versus placebo ) , and 50 % for patients in the 50 μg/kg group ( P = 0.006 versus placebo ) . Results of other endpoints , including pain on swallowing and use of pain medication specifically for mucositis , suggested a better outcome for patients in the 50 μg/kg group compared with the placebo and 25 μg/kg groups . Conclusions : Repifermin was well tolerated . Repifermin given before and after auto-HSCT seems to be active in reducing mucositis , but a larger trial will be necessary to determine the efficacy of repifermin with this dose schedule We have conducted a prospect i ve controlled r and omised clinical study testing for the efficacy of topical GM-CSF ( molgramostim ) , as compared to the combined topical use of an antiseptic agent ( povidone-iodine ) and amphotericin B ( AA ) in patients with chemotherapy-induced mucositis World Health Organization ( WHO ) grade s I-III . 31 patients ( 17 females , 14 males ) developing oral mucositis following the administration of 5-fluorouracil (5-FU)-based chemotherapy were entered into the present trial . 15 patients were r and omised to receive GM-CSF mouthwashes , whereas 16 patients were r and omised into the control arm to receive AA . Reported history ( P=0.6109 ) and grading of oral mucositis ( 2.1+/-0.7 , respectively ; P=0.9867 ) were balanced and equally distributed between the two groups . The mean size of lesions of oral mucositis was 1.5+/-0.6 cm ( range : 0.7 - 2.5 cm ) in the GM-CSF group and 1.2+/-0.5 cm ( range : 0.5 - 2.5 cm ) in the AA group ( P=0.08 ) , respectively . The mean number of oral mucositis lesions was 1.9+/-1.1 ( range : 1 - 4 ) in the GM-CSF group and 2.1+/-1.2 ( range : 1 - 4 ) in the AA group ( P=0.63 ) , respectively . None of the patients had previously received colony stimulating factors either topically or systemically . Treatment for oral mucositis was initiated on day 2.7+/-1.2 ( range : day 1 - 8 ) after onset of symptoms in the GM-CSF group and on day 1.8+/-1.4 ( range : day 1 - 3 ; P=0.11 ) in the AA group . The topical application of GM-CSF result ed in a significantly shorter duration and quicker resolution of oral mucositis , as compared to AA including both , pretreatment plus treatment periods ( 5.3+/-2.5 versus 8.1+/-1.5 days ; P=0.0008 ) as well as the necessary duration of treatment needed until complete remission of lesions ( 2.8+/-0.7 versus 6.3+/-1.1 days ; P<0.0001 ) . A systemic effect of topical GM-CSF upon the number of peripheral blood leukocytes or granulocytes was excluded . We conclude that the topical application of GM-CSF by mouthwash significantly abbreviated the duration and relieved patients from symptoms of chemotherapy-induced mucositis and was superior to the topical application of AA PURPOSE Based on early clinical evidence of potential mucosal protection by granulocyte-macrophage colony stimulating factor ( GM-CSF ) , the Radiation Therapy Oncology Group conducted a double-blind , placebo-controlled , r and omized study to test the efficacy and safety of GM-CSF in reducing the severity and duration of mucosal injury and pain ( mucositis ) associated with curative radiotherapy ( RT ) in head- and -neck cancer patients . METHODS AND MATERIAL S Eligible patients included those with head- and -neck cancer with radiation ports encompassing > 50 % of oral cavity and /or oropharynx . St and ard RT ports were used to cover the primary tumor and regional lymphatics at risk in st and ard fractionation to 60 - 70 Gy . Concurrent cisplatin chemotherapy was allowed . Patients were r and omized to receive subcutaneous injection of GM-CSF 250 microg/m2 or placebo 3 times a week . Mucosal reaction was assessed during the course of RT using the National Cancer Institute Common Toxicity Criteria and the protocol -specific scoring system . RESULTS Between October 2000 and September 2002 , 130 patients from 36 institutions were accrued . Nine patients ( 7 % ) were excluded from the analysis , 3 as a result of drug unavailability . More than 80 % of the patients participated in the quality -of-life endpoint of this study . The GM-CSF did not cause any increase in toxicity compared with placebo . There was no statistically significant difference in the average mean mucositis score in the GM-CSF and placebo arms by a t test ( p = 0.4006 ) . CONCLUSION This placebo-controlled , r and omized study demonstrated no significant effect of GM-CSF given concurrently compared with placebo in reducing the severity or duration of RT-induced mucositis in patients undergoing definitive RT for head- and -neck cancer Preliminary studies in allogeneic BMT suggest that recombinant human granulocyte-macrophage colony-stimulating factor ( rhGM-CSF ) is well tolerated . This is a prospect i ve , multicenter , r and omized , double-blind , placebo-controlled trial . Yeast-derived rhGM-CSF 250 micrograms/m2/day or placebo was administered by 4-hour i.v . infusion starting on the day of marrow infusion ( day 0 ) to day 20 . All patients received HLA-identical sibling marrow and cyclosporine and prednisone for GVHD prophylaxis . Fifty three patients received rhGM-CSF and 56 received placebo . Comparison of demographics revealed no differences . The time to achieve an absolute neutrophil count of > 0.5 x 10(9 ) cells/l was shortened in rhGM-CSF treated patients ( day 13 vs. 17 , P = 0.0001 ) . The incidences of grade III-IV mucositis and infection were significantly reduced ( P = 0.005 , P = 0.001 , respectively ) and duration of hospitalization was modestly shortened by 1 day ( P = 0.02 ) in rhGM-CSF treated patients . No differences in platelet recovery , erythrocyte recovery , incidence of veno-occlusive disease , GVHD severity , relapse or survival were observed . In conclusion , rhGM-CSF is well tolerated and reduces post-transplant morbidity in patients undergoing HLA-identical allogeneic BMT Twenty-nine previously untreated patients with squamous cell carcinoma of the oral cavity and pharynx underwent a treatment program with four courses of chemotherapy alternated with three courses of radiotherapy . Granulocyte-macrophage colony-stimulating factor ( GM-CSF ) was administered at a dose of 5 micrograms/mg subcutaneously on the same day as radiation treatment in order to prevent mucositis . No grade 4 mucositis was reported ; only four episodes of grade 2 mucositis and thirteen grade 2 . Comparing these results with historical patients treated with the same chemotherapy-radiation program but without GM-CSF , the authors concluded that GM-CSF is an effective treatment for preventing mucositis produced by chemotherapeutic and /or radiotherapeutic interventions in patients at high risk of oropharyngeal mucosal damage Uncontrolled clinical trials have shown that parenteral administration of GM-CSF reduces the frequency of chemotherapy-induced mucositis . The mechanism of this effect could be related to acceleration of haematopoiesis and /or increase in functional activation of WBC . We conducted a double-blind , placebo-controlled , dose ranging study of GM-CSF ( mol-gramostim ) mouthwash in patients with breast cancer during the first treatment cycle of a combination chemotherapy regimen which has historically produced dose-limiting ( grade > or = 3 ) mucositis in approximately 39 % of patients . Subjects were r and omized to receive either placebo mouthwash ( 0.1 percent albumin ) or one of four concentrations of GM-CSF mouthwash ( 0.01 , 0.1 , 1.0 or 10 mcg/ml ) . The primary endpoint was to evaluate the relationship between dose of GM-CSF mouthwash received and probability of grade > or = 3 mucositis using a logistic model . Solutions were administered four times daily starting within 24 hours of chemotherapy initiation and continuing until the end of the cycle ( day 21 ) . Mucositis was assessed on days 1 - 6 , 10 , 15 and 21 . Day 6 plasma sample s were assayed for GM-CSF . Forty-five patients were evaluable for response ( nine per dosing group ) . A 42 % risk ( 15/36 ) of mucositis grade > or = 3 was evident on day 15 in patients receiving GM-CSF compared to 2 of 9 patients on the placebo arm . No evidence of dose response was found by logistic regression . Five patients had a detectable plasma concentration of GM-CSF ( 56 - 209 pg/ml ) . A positive correlation between GM-CSF dose and leukocyte recovery was noted ( P = 0.04 ) PURPOSE To describe patient-reported outcomes of mouth and throat soreness ( MTS ) and related sequelae on daily activities from a phase III study of palifermin in the autologous hematopoietic stem-cell transplantation ( HSCT ) setting and to compare patient self-evaluations with clinicians ' assessment s of oral mucositis using objective scales . PATIENTS AND METHODS Patients ( n = 212 ) received palifermin ( 60 microg/kg/d ) or placebo for 3 days before total-body irradiation ( 12 Gy ) , etoposide 60 mg/kg , and cyclophosphamide 100 mg/kg , and 3 days after HSCT . Patients completed a daily question naire ( Oral Mucositis Daily Question naire [ OMDQ ] ) evaluating MTS severity and its effects on daily functional activities . Patients ' self- assessment data were compared with clinicians ' assessment s of oral mucositis using the objective scales . RESULTS Palifermin reduced the incidence and duration of severe oral mucositis , as assessed by both clinicians and patients . Comparisons between patient and clinician assessment s demonstrated that the average daily scores between mucositis grade and subjective ( MTS ) instruments were similar , although patients reported MTS onset , peak , and resolution earlier ( 1 to 3 days ) than clinicians ' assessment s. Patients receiving palifermin reported statistically significant improvements ( P < .001 ) in daily functioning activities ( swallowing , drinking , eating , talking , sleeping ) and required significantly less narcotic opioids ( P < .001 ) ; improvement in the patient 's overall physical and functional well-being was also reported . This was confirmed by the results of the Functional Assessment of Cancer Treatment question naire . CONCLUSION These results support the clinical benefit of palifermin in the HSCT setting , providing evidence that a patient 's self- assessment instrument ( OMDQ ) may serve as an alternative tool to assess oral mucositis severity in clinical trials In the present open non-r and omized phase II study we looked for effectiveness , safety , tolerability and costs of locally applied GM-CSF in preventing or treating mucositis in patients receiving chemotherapy or chemoradiotherapy for head and neck cancer . In addition to clinical mucositis scoring system , the effects of treatment with GM-CSF were evaluated by its impact on patient quality of life and by laboratory immunological assays such as serum proinflammatory cytokines , IL-2 and leptin . The trial was design ed to assess the effectiveness of local GM-CSF treatment in two different setting s : i ) prophylaxis of mucositis ; ii ) treatment of mucositis . Prophylaxis was chosen for chemoradiotherapy treatments of high mucosatoxic potential , while curative treatment was reserved for chemotherapy or chemoradiotherapy treatments of lesser potential of inducing mucositis . From January 1998 to December 2001 , 68 patients entered the study . The great majority of patients of both groups had head and neck cancer , were stage IV , PS ECOG 0 - 1 , were habitual smokers and were treated with chemotherapy and concomitant ( or sequential ) chemoradiotherapy . Forty-six patients were included in the ' prophylactic ' setting and 22 patients in the ' curative ' setting . The main findings of our study are : only 50 % of patients included in the ' prophylactic ' setting developed mucositis ; the duration of oral mucositis from appearance until complete remission was significantly shorter in the ' prophylactic ' than in the ' curative ' setting ; the mean grade of oral mucositis at baseline , on day 3 of therapy and on day 6 of therapy was significantly lower in the ' prophylactic ' than in the ' curative ' setting ; 24 ( 55.82 % ) patients in the ' prophylactic ' setting had grade 3/4 oral mucositis at baseline compared to 25 ( 80.60 % ) patients in the ' curative ' setting ( p=0.048 ) . Thirteen ( 30.23 % ) patients in the ' prophylactic ' setting had grade 3/4 oral mucositis on day 3 of therapy compared to 19 ( 61.29 % ) patients in the ' curative ' setting ( p=0.015 ) ; ' prophylactic ' setting was able to shorten grade 3/4 oral mucositis to grade 0/1 more effectively than the ' curative ' one on day 6 of therapy ( p=0.05 ) . The present clinical trial is to date by far the largest study assessing the effectiveness of topical GM-CSF and it is the first study comparing the efficacy of topical GM-CSF in the ' prophylactic ' setting , i.e. , with the aim to prevent the chemoradiotherapy-induced oral mucositis , with that in the ' curative ' treatment , i.e. , the therapy for established oral mucositis . The topical application of GM-CSF was demonstrated to be effective for oral mucositis induced by chemotherapy and chemoradiotherapy regimens . Moreover , the ' prophylactic ' setting was demonstrated to be more effective than the ' curative ' one Mucositis , the inflammation and necrosis of mucosal membranes , is a serious and debilitating consequence of many cancer therapies . We were interested in the potential role of filgrastim ( recombinant methionyl human granulocyte colony-stimulating factor , r-metHuG-CSF ) in the reduction of mucositis . Patients with newly diagnosed small-cell lung cancer ( SCLC ) were treated with CAE chemotherapy ( cyclophosphamide , doxorubicin , and etoposide ) and placebo or filgrastim . If patients had an episode of febrile neutropenia , they received unblinded filgrastim in subsequent CAE cycles . Oral mucositis was considered to have occurred if a patient reported any clinical sign or symptom of oral mucositis with or without oral c and idiasis . Oral mucositis was analyzed using the unadjusted chi-square test , and time to first episode of mucositis was analyzed using the stratified log-rank test as well as the Cox proportional hazards regression model . During cycle 1 , placebo-treated patients had more episodes of mucositis ( 47 % ) compared with those patients r and omized to filgrastim ( 28 % ) . Across all cycles of treatment , 70 % of placebo-treated patients experienced mucositis , compared with 53 % of patients r and omized to filgrastim . A significant reduction in the incidence of chemotherapy-related oral mucositis occurred across multiple cycles of treatment in patients treated with filgrastim PURPOSE Based on the clinical evidence of mucosal protection by GM-CSF during cytotoxic chemotherapy , a pilot study was undertaken to determine the safety and mucosal reaction of patients receiving GM-CSF while undergoing definitive conventional fractionated radiotherapy in head and neck carcinoma . METHODS AND MATERIAL S Patients were considered eligible if buccal mucosa and oropharynx were included in the teleradiation field . Ten adult patients with squamous cell carcinoma of head and neck ( buccal mucosa--8 and posterior 1/3 tongue--2 ) were entered into the trial . Radiation therapy was delivered with telecobalt machine at conventional 2 Gy fraction and 5 fractions/week . The radiation portals consisted of two parallel opposing lateral fields . GM-CSF was given subcutaneously at a dose of 1 microg/kg body weight , daily , after 20 Gy until the completion of radiation therapy . Patients were evaluated daily for mucosal reaction , pain , and functional impairment . RESULTS The median radiation dose was 66 Gy . Eight patients received > or = 60 Gy . The tolerance to GM-CSF was good . All 10 patients completed the planned daily dose of GM-CSF without interruption . Mucosal toxicity was Grade I in four patients till the completion of radiotherapy ( dose range 50 - 66 Gy ) . Six patients developed Grade II reaction , fibrinous mucosal lesions of maximum size 1.0 - 1.5 cm , during radiotherapy . None developed Grade III mucositis . The maximum mucosal pain was Grade I during GM-CSF therapy . In two patients after starting GM-CSF the pain reduced in intensity . Functional impairment was mild to moderate . All patients were able to maintain adequate oral intake during the treatment period . Total regression of mucosal reaction occured within 8 days following completion of radiotherapy . CONCLUSIONS GM-CSF administration concurrently with conventional fractionated radiotherapy was feasible without significant toxicity . The acute side effects of radiotherapy namely mucositis , pain , and functional impairment were nil to minimal . The results are suggestive of mucosal protection by GM-CSF during radiotherapy and warrants further study in r and omized double blind trial This article describes the system for rating the quality of medical evidence developed and used during creation of the Agency for Health Care Policy and Research -sponsored heart failure guideline . Previous approaches to rating evidence were not design ed for use in the setting of clinical practice guidelines . The present system is based on the tenet that flaws in research design are serious to the extent they threaten the validity of the results of studies . A taxonomy of major and minor flaws based on that tenet was developed for r and omized controlled trials and for cohort and medical registry studies . The use of the system is described in the context of two difficult clinical issues considered by the Panel : the role of coronary artery revascularization and the use of metoprolol OBJECTIVE The aim of this open trial was to test the efficacy of granulocyte-macrophage colony-stimulating factor ( GM-CSF ) mouthrinses as a potential treatment in reducing the duration of severe oral mucositis in patients undergoing bone marrow transplantation for hematologic malignancies . STUDY DESIGN The study group was composed of 10 consecutive patients suffering from severe oral mucositis during bone marrow transplantation procedures . The control group was similar to the study group in age and gender and comprised 29 historical patients with similar clinical characteristics . Freshly prepared GM-CSF mouthwash ( 0.5 microg/mL ) was administered to the study population for 1 minute 3 times per day after oral hygiene procedures , starting from the first day of mucositis until clinical improvement of oral lesions . The study and control population s were compared with respect to duration of severe oral mucositis ( 1 - 9 days , 10 - 19 days , > or = 20 days ) . RESULTS There was no statistically ( chi2 exact test ) significant difference in mean mucositis score between the study group ( 11.9+/-6.1 ) and the control group ( 16.6+/-8.9 ) . However , the duration of severe mucositis appeared to be reduced ; 60 % of the GM-CSF mouthrinse patients had severe mucositis for less than 9 days , whereas only 28 % of the controls had severe mucositis for less than 9 days . In addition , 10 % of the GM-CSF mouthrinse patients experienced severe mucositis lasting 20 or more days , whereas 34 % of the controls experienced severe mucositis for 20 or more days . CONCLUSIONS These findings suggest that GM-CSF may reduce the duration of severe mucositis , but controlled , double-blind clinical trials are now required PURPOSE Acute mucositis is a dose-limiting toxicity of concurrent chemoradiotherapy regimens for locally advanced head and neck cancer . Palifermin ( a recombinant human keratinocyte growth factor ; DeltaN23-KGF ) stimulates the proliferation and differentiation of mucosal epithelium to reduce mucositis in patients receiving intensive therapy for hematologic cancers . This study assessed the efficacy and safety of palifermin in patients receiving concurrent chemoradiotherapy for advanced head and neck squamous cell carcinoma . PATIENTS AND METHODS In a phase II trial , st and ard radiotherapy was delivered in daily 2-Gy fractions to 70 Gy , or hyperfractionated radiotherapy was delivered in 1.25-Gy fractions twice daily to 72 Gy , over 7 weeks . Chemotherapy included cisplatin 20 mg/m(2 ) for 4 days and continuous-infusion fluorouracil 1,000 mg/m(2)/d for 4 days on weeks 1 and 5 of irradiation . Patients were r and omly assigned 2:1 to palifermin 60 microg/kg or placebo once weekly for 10 doses . A follow-up trial evaluated long-term survival . RESULTS Sixty-seven patients received palifermin and 32 received placebo . The median duration of grade > or= 2 mucositis was 6.5 and 8.1 weeks in the palifermin and placebo groups , respectively ( P = .157 ) . Palifermin appeared to reduce mucositis , dysphagia , and xerostomia during hyperfractionated radiotherapy ( n = 40 ) but not st and ard radiation therapy ( n = 59 ) . Adverse events were similar between treatment groups . Palifermin did not alter tumor response or survival . CONCLUSION Ten once-weekly doses of palifermin at 60 microg/kg were well tolerated . Most patients completed treatment , but palifermin did not reduce the morbidity of concurrent chemotherapy and radiotherapy . Future studies should evaluate higher palifermin doses with longer and more st and ardized assessment of acute mucositis |
12,906 | 26,330,200 | The analysis establishes that differences in processing protocol s and cooking practice s modify the glycaemic response to foods made with whole-grain oats .
Smaller particle size and increased starch gelatinisation appear to increase the glycaemic response | Whole-grain oats have been identified as a type of food that blunts blood glucose increase after a meal .
However , processing of oats changes the physical characteristics of the grain , which may influence human glycaemic response .
Therefore , the effect of different processes on acute postpr and ial glycaemic response , quantified using glycaemic index ( GI ) measurements , was investigated in a systematic review . | Background Reductions in postpr and ial glycemia have been demonstrated previously with the addition of the novel viscous polysaccharide ( NVP ) , PolyGlycopleX ® ( PGX ® ) , to an OGTT or white bread . This study explores whether these reductions are sustained when NVP is added to a range of commonly consumed foods or incorporated into a breakfast cereal . Methods Ten healthy subjects ( 4 M , 6F ; age 37.3 ± 3.6 y ; BMI 23.8 ± 1.3 kg/m2 ) , participated in an acute , r and omized controlled trial . The glycemic response to cornflakes , rice , yogurt , and a frozen dinner with and without 5 g of NVP sprinkled onto the food was determined . In addition , 3 granolas with different levels of NVP and 3 control white breads and one white bread and milk were also consumed . All meals contained 50 g of available carbohydrate . Capillary blood sample s were taken fasting and at 15 , 30 , 45 , 60 , 90 and 120 min after the start of the meal . The glycemic index ( GI ) and the glycemic reduction index potential ( GRIP ) were calculated . The blood glucose concentrations at each time and the iAUC values were subjected to repeated- measures analysis of variance ( ANOVA ) examining for the effect of test meal . After demonstration of significant heterogeneity , differences between individual means was assessed using GLM ANOVA with Tukey test to adjust for multiple comparisons . Results Addition of NVP reduced blood glucose response irrespective of food or dose ( p < 0.01 ) . The GI of cornflakes , cornflakes+NVP , rice , rice+NVP , yogurt , yogurt+NVP , turkey dinner , and turkey dinner+NVP were 83 ± 8 , 58 ± 7 , 82 ± 8 , 45 ± 4 , 44 ± 4 , 38 ± 3 , 55 ± 5 and 41 ± 4 , respectively . The GI of the control granola , and granolas with 2.5 and 5 g of NVP were 64 ± 6 , 33 ± 5 , and 22 ± 3 respectively . GRIP was 6.8 ± 0.9 units per/g of NVP . ConclusionS prinkling or incorporation of NVP into a variety of different foods is highly effective in reducing postpr and ial glycemia and lowering the GI of a food . Clinical Trial registration NCT00935350 Differences in glycemic responses to various starchy foods are related to differences in the rate of starch digestion and absorption . In this study , the importance of the degree of gelatinization and the product thickness for postpr and ial glycemic and insulinemic responses to rolled oats and barley were studied in healthy subjects ( 5 men and 5 women ) . Thick ( 1.0 mm ) rolled oats were made from raw or preheated ( roasted or steamed ) kernels . In addition , thin ( 0.5 mm ) rolled oats were made from roasted or roasted and steamed ( processed under conditions simulating commercial production ) oat kernels . Finally , steamed rolled barley kernels ( 0.5 or 1.0 mm ) were prepared . All thin flakes elicited high glucose and insulin responses [ glycemic index ( GI ) , 88 - 118 ; insulinemic index ( II ) , 84 - 102 ] , not significantly different from white wheat bread ( P : > 0.05 ) . In contrast , all varieties of thick oat flakes gave significantly lower metabolic responses ( GI , 70 - 78 ; II , 58 - 77 ) than the reference bread ( P : < 0.05 ) . Thick barley flakes , however , gave high glucose and insulin responses ( GI , 94 ; II , 84 ) , probably because the botanical structure underwent more destruction than the corresponding oat flakes . We conclude that minimal processing of oat and barley flakes had a relatively minor effect on GI features compared with the more extensive commercial processing . One exception was thick oat flakes , which in contrast to the corresponding barley flakes , had a low GI BACKGROUND Method ologic choices affect measures of the glycemic index ( GI ) . The effects on GI values of blood sampling site , reference food type , and the number of repeat tests have been insufficiently determined . OBJECTIVE The objective was to study the effect of method ologic choices on GI values . Comparisons were made between venous and capillary blood sampling and between glucose and white bread as the reference food . The number of tests needed for the reference food was assessed . Rye bread , oatmeal porridge , and instant mashed potato were used as the test foods . DESIGN Twelve healthy volunteers were served each test food once and both reference foods 3 times at 1-wk intervals in a r and om order after they had fasted overnight . Capillary and venous blood sample s were drawn at intervals for 3 h after each study meal . RESULTS GIs and their CVs based on capillary sample s were lower than those based on venous sample s. Two tests of glucose solution as the reference provided stable capillary GIs for the test foods . The capillary GIs did not differ significantly when white bread was used as the reference 1 , 2 , or 3 times , but the variation was lower when tests were performed 2 and 3 times . Capillary GIs with white bread as the reference were 1.3 times as high as those with glucose as the reference . The capillary GIs of rye bread , oatmeal porridge , and mashed potato were 77 , 74 , and 80 , respectively , with glucose as the reference . CONCLUSIONS Capillary blood sampling should be used in the measurement of GI , and reference tests with glucose or white bread should be performed at least twice Reliable tables of glycemic index ( GI ) compiled from the scientific literature are instrumental in improving the quality of research examining the relation between GI , glycemic load , and health . The GI has proven to be a more useful nutritional concept than is the chemical classification of carbohydrate ( as simple or complex , as sugars or starches , or as available or unavailable ) , permitting new insights into the relation between the physiologic effects of carbohydrate-rich foods and health . Several prospect i ve observational studies have shown that the chronic consumption of a diet with a high glycemic load ( GI x dietary carbohydrate content ) is independently associated with an increased risk of developing type 2 diabetes , cardiovascular disease , and certain cancers . This revised table contains almost 3 times the number of foods listed in the original table ( first published in this Journal in 1995 ) and contains nearly 1300 data entries derived from published and unpublished verified sources , representing > 750 different types of foods tested with the use of st and ard methods . The revised table also lists the glycemic load associated with the consumption of specified serving sizes of different foods The determine the effect of different foods on the blood glucose , 62 commonly eaten foods and sugars were fed individually to groups of 5 to 10 healthy fasting volunteers . Blood glucose levels were measured over 2 h , and expressed as a percentage of the area under the glucose response curve when the same amount of carbohydrate was taken as glucose . The largest rises were seen with vegetables ( 70 + /- 5 % ) , followed by breakfast cereals ( 65 + /- 5 % ) , cereals and biscuits ( 60 + /- 3 % ) , fruit ( 50 + /- 5 % ) , dairy products ( 35 + /- 1 % ) , and dried legumes ( 31 + /- 3 % ) . A significant negative relationship was seen between fat ( p less than 0.01 ) and protein ( p less than 0.001 ) and postpr and ial glucose rise but not with fiber or sugar content The primary aim of the present study was to exp and the glycaemic index ( GI ) data base by determining the GI and insulin index values of thirty-nine foods containing sugars in healthy adults . The second aim was to examine the hypothesis that glycaemic and insulin responses to foods which contain added sugar(s ) are higher than responses to foods containing naturally-occurring sugars . Eight healthy subjects drawn from a pool of eighteen consumed 50 g carbohydrate portions ( except 25 g carbohydrate portions for fruits ) of the test foods . The GI and insulin index were determined according to st and ardized methodology and expressed on a scale on which glucose = 100 . The median GI and insulin index values of all foods tested were 56 ( range 14 to 80 ) and 56 ( range 24 to 124 ) respectively . The median GI of the foods containing added sugars was similar to that of foods containing naturally-occurring sugars ( 58 v. 53 respectively , P = 0.08 ) . Likewise , the median insulin index of the foods containing added sugars was not significantly different from that of foods containing naturally-occurring sugars ( 61 v. 56 respectively , P = 0.16 ) . There was no evidence of ' rebound hypoglycaemia ' or excessive insulin secretion relative to the glucose response . We conclude that most foods containing sugars do not have a high GI . In addition , there is often no difference in responses between foods containing added sugars and those containing naturally-occurring sugars Objective : To determine the glycaemic index ( GI ) of various staple carbohydrate-rich foods in the UK diet , and to consider the factors influencing the GI of foods . Design : Subjects were served with 25 or 50 g portions of glucose on three occasions , followed by a selection of test foods providing an equal amount of available carbohydrate , in r and om order . Each test food was consumed by 10 subjects . Capillary blood glucose levels were measured in the fasted state and over the 120 min following commencement of consumption of the foods . Setting : The study was carried out in a research institute ( MRC Human Nutrition Research , Cambridge , UK).Subjects : Forty-two healthy adult volunteers were studied . Methods : The GI values of 33 foods were measured according to the WHO/FAO recommended methodology . These foods included various breads , breakfast cereals , pasta , rice and potatoes , all of which were commercially available in the UK . Conclusions : The results illustrate a number of factors which are important in influencing the GI of a food , highlighting the importance of measuring the GI of a food , rather than assuming a previously published value for a similar food . This is useful both to research ers analysing dietary surveys or planning intervention studies , and also to health professionals advising individuals on their diets AIM To determine the glycaemic index values to a range of foods that are unique to New Zeal and , and those that are grown and /or manufactured locally . METHODS We determined the glycaemic index of 28 carbohydrate foods in both healthy subjects and those with type 2 diabetes . Venous blood sample s were collected over two to three hours , and the incremental area under the blood glucose curve was used to calculate glycaemic index values . RESULTS AND CONCLUSIONS This study has identified the glycaemic index values for a range of New Zeal and foods which will be clinical ly useful in the nutritional management of individuals with diabetes mellitus . People with diabetes are recommended to choose foods with a low glycaemic index which is associated with optimal blood glucose control and lipid levels The effect of plasma glucose on satiety and the capacity of carbohydrates to stimulate cholecystokinin ( CCK ) remain unclear . The aim of this study was to test the hypothesis that the magnitude of the postpr and ial plasma glucose and insulin response is inversely related to the CCK response and to subjective satiety . Seven healthy , male volunteers consumed equal carbohydrate portions ( 0.5 g/kg body weight ) of six test meals ( Rice Bubbles , Sustain , Vita-Brits , All-Bran , porridge and white bread ) in r and om order after an overnight fast . An egg and bacon meal was consumed as a non-carbohydrate control providing 0.5 g protein/kg body weight . Serum CCK , plasma glucose and insulin and subjective satiety ( measured by a rating scale ) were assessed over 3 h and quantified using the glycaemic index ( GI ) , insulin index ( II ) , the peak satiety score and area under the incremental curve ( AUC ) . The observed GIs ( mean + /- SE ) ranged from 42.5 + /- 2.6 for All-Bran to 116.2 + /- 11.4 for Rice Bubbles , using white bread as the reference food ( GI = 100 ) . Peak satiety scores varied eightfold from 0.21 + /- 0.4 for Sustain to 1.64 + /- 0.4 for All-Bran . Significant inverse relationships were observed between the peak satiety score and both the glycaemic and insulin index of the seven meals ( r = -0.916 , p less than 0.001 and r = -0.926 , p less than 0.001 ) . A direct relationship was observed between satiety ( AUC ) and the CCK response ( AUC ) ( r = 0.73 p less than 0.01 ) . The results suggest that glycaemic and insulin responses to carbohydrate foods are inversely proportional to the CCK response and satiety The objective of the present paper is to provide glycaemic index ( GI ) and glycaemic load ( GL ) values for a variety of foods that are commonly consumed in Hong Kong and exp and on the international GI table of Chinese foods . Fasted healthy subjects were given 50 g of available carbohydrate servings of a glucose reference , which was tested twice , and test foods of various br and s of noodles ( n 5 ) , instant cereals ( n 3 ) and breads ( n 2 ) , which were tested once , on separate occasions . For each test food , tests were repeated in ten healthy subjects . Capillary blood glucose was measured via finger-prick sample s in fasting subjects ( - 5 , 0 min ) and at 15 , 30 , 45 , 60 , 90 and 120 min after the consumption of each test food . The GI of each test food was calculated geometrically by expressing the incremental area under the blood glucose response curve ( IAUC ) of each test food as a percentage of each subject 's average IAUC for the reference food . GL was calculated as the product of the test food 's GI and the amount of available carbohydrate in a reference serving size . The majority of GI values of foods tested were medium ( a GI value of 56 - 69 ) to high ( a GI value of 70 or more ) and compared well with previously published values . More importantly , our data set provides GI values of ten foods previously untested and presents values for foods commonly consumed in Hong Kong |
12,907 | 24,402,784 | There is insufficient evidence that adding bupropion ( 12 trials , N = 3487 , RR 1.9 , 95 % CI 0.94 to 1.51 ) or nortriptyline ( 4 trials , N = 1644 , RR 1.21 , 95 % CI 0.94 to 1.55 ) to nicotine replacement therapy ( NRT ) provides an additional long-term benefit .
Bupropion has been associated with suicide risk , but whether this is causal is unclear .
Nortriptyline has the potential for serious side-effects , but none have been seen in the few small trials for smoking cessation .
The antidepressants bupropion and nortriptyline aid long-term smoking cessation .
Adverse events with either medication appear to rarely be serious or lead to stopping medication .
Evidence suggests that the mode of action of bupropion and nortriptyline is independent of their antidepressant effect and that they are of similar efficacy to nicotine replacement .
Evidence suggests that neither selective serotonin reuptake inhibitors ( e.g. fluoxetine ) nor monoamine oxidase inhibitors aid cessation | BACKGROUND There are at least three reasons to believe antidepressants might help in smoking cessation .
Firstly , nicotine withdrawal may produce depressive symptoms or precipitate a major depressive episode and antidepressants may relieve these .
Secondly , nicotine may have antidepressant effects that maintain smoking , and antidepressants may substitute for this effect .
Finally , some antidepressants may have a specific effect on neural pathways ( e.g. inhibiting monoamine oxidase ) or receptors ( e.g. blockade of nicotinic-cholinergic receptors ) underlying nicotine addiction .
OBJECTIVES The aim of this review is to assess the effect and safety of antidepressant medications to aid long-term smoking cessation . | INTRODUCTION We explored the differential effect of cessation interventions ( behavioral support sessions with [ BSS+ ] and without [ BSS ] bupropion ) between hookah and cigarette smokers . METHODS We reanalyzed the data from a major cluster-r and omized controlled trial , ASSIST ( Action to Stop Smoking In Suspected Tuberculosis ) , which consisted of 3 conditions : ( a ) behavioral support sessions ( BSS ) , ( b ) behavioral support sessions plus 7 weeks of bupropion therapy ( BSS+ ) , and ( c ) controls receiving usual care . The trial originally recruited 1,955 adult smokers with suspected tuberculosis from 33 health centers in the Jhang and Sargodha districts of Pakistan between 2010 and 2011 . The primary endpoint was continuous 6-month smoking abstinence , which was determined by carbon monoxide levels . Subgroup-specific relative risks ( RRs ) of smoking abstinence were computed and tested for differential intervention effect using log binomial regression ( generalized linear model ) between 3 subgroups ( cigarette-only : 1,255 ; mixed : 485 ; and hookah-only : 215 ) . RESULTS The test result for homogeneity of intervention effects between the smoking forms was statistically significant ( p-value for BSS+ : .04 and for BSS : .02 ) . Compared to the control , both interventions appeared to be effective among hookah smokers ( RR = 2.5 ; 95 % CI = 1.3 - 4.7 and RR = 2.2 ; 95 % CI = 1.3 - 3.8 , respectively ) but less effective among cigarette smokers ( RR = 6.6 ; 95 % CI = 4.6 - 9.6 and RR = 5.8 ; 95 % CI = 4.0 - 8.5 ) , respectively . CONCLUSIONS The differential intervention effects on hookah and cigarette smokers were seen ( a ) because the behavioral support intervention was design ed primarily for cigarette smokers ; ( b ) because of differences in demographic characteristics , behavioral , and sociocultural determinants ; or ( c ) because of differences in nicotine dependency levels between the 2 groups Abstract Many cancer patients continue to smoke postdiagnosis , which is associated with poorer clinical outcomes . Identifying prospect i ve predictors of smoking cessation among patients currently receiving smoking cessation treatment can help guide the development and implementation of smoking cessation programs with this population . Material and methods . Data from 246 cancer patients participating in a r and omized placebo-controlled smoking cessation clinical trial were used to examine baseline predictors of end-of-treatment and six-month postbaseline smoking cessation outcomes . Baseline demographic , smoking-related , disease-related , and psychological variables were examined as predictors of biochemically-confirmed point-prevalence abstinence . Results . Multivariate analysis indicated that , for end-of-treatment abstinence , patients were significantly more likely to have quit smoking if they were older ( OR = 1.06 , 95 % CI : 1.03–1.10 , p < 0.05 ) and were diagnosed with a non-tobacco related cancer ( OR = 2.54 , 95 % CI : 1.24–5.20 , p < 0.05 ) . Likewise , for six-month abstinence , patients were significantly more likely to have quit smoking if they were older ( OR = 1.04 , 95 % CI : 1.01–1.08 , p < 0.05 ) and were significantly less likely to have quit smoking if they were female ( OR = 0.47 , 95 % CI : 0.22–0.97 , p < 0.05 ) . Patients with tobacco-related cancers and female patients reported significantly higher levels of depression symptoms ( p < 0.05 ) , which proved predictive of smoking relapse . Conclusions . Patient age , gender , and cancer-type may be important factors to consider when developing and implementing smoking cessation interventions for cancer patients Abstract BACKGROUND : This study evaluated the efficacy of bupropion for relapse prevention in smokers with and without a past history of major depressive disorder . Changes in depressive symptoms were also examined . DESIGN : Data were gathered prospect ively from a r and omized , double-blind relapse prevention trial of bupropion conducted at five study sites . A total of 784 smokers ( 54 % female , 97 % white ) were enrolled . Using the Structured Clinical Interview for Depression , 17 % of the subjects reported a past history of major depressive disorder at baseline . All subjects received open-label bupropion SR ( 300 mg/d ) for 7 weeks . Subjects abstinent from smoking at the end of 7 weeks ( N=429 ) were r and omized to bupropion SR ( 300 mg/d ) or placebo for the remainder of the year and followed for 1 year off medication . The primary outcome measures were median time to relapse to smoking and the 7-day point-prevalence smoking abstinence rate . Self-reported abstinence from smoking was verified by expired air carbon monoxide . The Beck Depression Inventory was used to assess depressive symptoms at baseline and at weeks 8 and 12 . RESULTS : Median time to relapse did not differ by past history of major depressive disorder . Bupropion was associated with higher point-prevalence smoking abstinence at the end of medication compared to placebo ( P=.007 ) , independent of a past history of major depressive disorder . Moreover , change in depressive symptoms during the double-blind phase did not differ for those with and without a past history of major depressive disorder . CONCLUSIONS : Extended use of bupropion for relapse prevention is effective for smokers with and without a history of major depression OBJECTIVE To evaluate the potential efficacy of bupropion sustained release when used in combination with minimal counseling for moist snuff cessation in males . METHODS A double-blind , placebo-controlled 3-month trial . The active treatment group ( n = 35 ) received bupropion SR at 150 mg/qd day for the first 3 days , then beginning day 4 through day 49 ( 7 weeks ) 150 mg/ b.i.d . The placebo group ( n= 35 ) received 1 tablet qd for 3 days and beginning day 4 through day 49 , 1 tablet/b.i.d . RESULTS Bupropion 300 mg/day ( 150 b.i.d . ) produced significantly higher quit rates for smokeless tobacco cessation at the end of treatment ( 7 weeks ) than placebo ( p = 0.04 ) with an OR of 2.73 . CONCLUSION Bupropion SR appears to be effective for smokeless tobacco cessation Stopping smoking is the only known method to slow down the inevitable progression of COPD . Early detection of the disease in smokers at risk of COPD gives a unique opportunity to prevent the disease progression . The aim of the study was to evaluate the effects of smoking intervention in a group of subjects with newly diagnosed airflow limitation ( AL ) . Of 558 current smokers participating in population spirometric screening for COPD combined with smoking cessation advice , 297 were diagnosed to have AL ( FEV1/FVC < 0.7 ) . After one year 193 presented for follow-up visit . Thirty subjects ( 10.1 % ) quit smoking . Remaining 163 smokers were invited to smokers ' clinic . Attendees ( n = 70 ) , 40 males , and 30 females , mean age 56 years , were r and omized at visit 1 to treatment with nicotine patch ( n = 38 ) or bupropion SR ( n = 32 ) . Follow-up was scheduled at 2 weeks , at the end of treatment , 6 months and 12 months . After 12 months a phone call assessed the smoking status . Non smoking was vali date d with carbon monoxide measurements in exhaled air . Patients who did not attend the follow-up visits were considered smokers . The number of participants at follow-up decreased significantly : from 70 subjects at visit one to 57 after 2 weeks , 34 at end of treatment and 14 subjects at months . Almost all ( n = 69 ) were reached at 12 month by the phone . The vali date d quit rate after 12 months was 18.5 % ( 13/70 ) , 8 in group treated with nicotine patch and 5 in the group treated with bupropion SR ( NS ) . When total group of smokers with newly diagnosed COPD was considered 10 % quit smoking as result of minimal intervention with another 4.5 % after pharmacological treatment The authors present results of a r and omized clinical trial of the efficacy of extended treatment with bupropion SR in producing longer term cigarette smoking cessation . Adult smokers ( N = 362 ) received open-label treatment ( 11 weeks ) that combined relapse prevention training , bupropion SR , and nicotine patch followed by extended treatment ( 14 weeks ) with bupropion SR or matching placebo . Abstinence percentages were relatively high ( week 11 : 52 % ; week 25 : bupropion , 42 % ; placebo , 38 % ; week 52 : bupropion , 33 % ; placebo , 34 % ) , but bupropion SR did not surpass placebo . Gender and baseline craving level were identified as significant , independent moderators of treatment response . Men were more likely to abstain than women ( week 11 : 59 % vs. 43 % , p = .001 ; week 25 : 48 % vs. 31 % , p = .001 ; week 52 : 39 % vs. 27 % , p = .01 ) . Because most smokers suffer relapse with any current cessation treatment , the comparatively high abstinence percentages achieved in this trial are of interest PURPOSE AND METHODS Cognitive behavior therapy ( CBT ) constitutes the basis of smoking cessation programs . Quitting rates are usually increased by the concomitant use of CBT and pharmacotherapy . There are studies showing the efficacy of bupropion and nortriptyline compared to placebo , but there is just one published comparison between these drugs , unfortunately with low power to detect significant differences . This study was design ed to compare the efficacy of bupropion , nortriptyline and placebo in a group of smokers who also received intensive counseling therapy . We conducted a double blind , double-dummy , placebo-controlled trial for smoking cessation that lasted 9 weeks . Patients were r and omized to receive nortriptyline 75 mg/day ( 52 subjects ) , bupropion 300 mg/day ( 53 subjects ) or placebo ( 51 subjects ) . All smokers also received the same intensive cognitive behavior therapy . The target day for quitting smoking was usually day 10 . Intensive counseling was provided at baseline , weekly during treatment , and at 10 , 13 , 16 , 20 and 26 weeks . Abstinence was defined as continuous when the subject was not smoking since the target-quitting day ( self-report ) and had an expired carbon monoxide concentration of 10 ppm or less . RESULTS The sustained abstinence rates at 6 months were 21.6 % in the placebo group , 30.8 % in the nortriptyline group ( p = 0.40 ) , and 41.5 % in the bupropion group ( p = 0.05 ) . The odds ratio was not statistically different for smokers using nortriptyline or bupropion ( OR 1.60 ; 95 % CI 0.66 - 3.86 ; p = 0.35 ) . The most common adverse events were dry mouth and drowsiness in the nortriptyline group and dry mouth and insomnia in the bupropion group . CONCLUSIONS Treatment with CBT + bupropion result ed in a better 6-month rate of smoking cessation compared to CBT+nortriptyline or CBT + placebo . Abstinence rate in the nortriptyline group was not statistically different from patients in the bupropion or placebo group Treatments that reduce the immediate effects of smoking withdrawal have potential for helping smokers quit . Serotonin-enhancing substances , such as tryptophan and high-carbohydrate diets , have been used in clinical disorders to relieve negative affect , a classic symptom of cigarette withdrawal . This research project investigated the use of tryptophan ( 50 mg/kg/day ) and high-carbohydrate diets , together with more traditional smoking cessation treatment techniques , to ameliorate the smoking withdrawal syndrome and to improve abstinence rates . Subjects were r and omly assigned to receive either tryptophan ( n=16 ) or placebo ( n=15 ) . St and ard smoking cessation treatment was identical for the experimental and control groups and consisted of four 2-hr weekly sessions of multicomponent group therapy . Smoking behavior , symptoms of nicotine withdrawal , and negative affect were assessed during a 2-week withdrawal period . Tryptophan-treated subjects who could not fully abstain were able to smoke fewer daily cigarettes . Reported anxiety and other withdrawal symptoms were lower in the tryptophan group compared with control subjects . These data suggest that serotonin-enhancing substances show promise for use as an adjunct to existing smoking cessation programs BACKGROUND Currently available smoking cessation therapies have limited success rates . Varenicline tartrate is a novel , selective nicotinic receptor partial agonist developed specifically for smoking cessation . This study evaluated the efficacy , tolerability , and safety of 3 varenicline doses for smoking cessation . Bupropion hydrochloride was included as an active control . METHODS A phase 2 , multicenter , r and omized , double-blind , placebo-controlled study of healthy smokers ( 18 - 65 years old ) . Subjects were r and omized to varenicline tartrate , 0.3 mg once daily ( n = 128 ) , 1.0 mg once daily ( n = 128 ) , or 1.0 mg twice daily ( n = 127 ) , for 6 weeks plus placebo for 1 week ; to 150-mg sustained-release bupropion hydrochloride twice daily ( n = 128 ) for 7 weeks ; or to placebo ( n = 127 ) for 7 weeks . RESULTS During the treatment phase , the continuous quit rates for any 4 weeks were significantly higher for varenicline tartrate , 1.0 mg twice daily ( 48.0 % ; P<.001 ) and 1.0 mg once daily ( 37.3 % ; P<.001 ) , than for placebo ( 17.1 % ) . The bupropion rate was 33.3 % ( P = .002 vs placebo ) . The carbon monoxide-confirmed continuous quit rates from week 4 to week 52 were significantly higher in the varenicline tartrate , 1.0 mg twice daily , group compared with the placebo group ( 14.4 % vs 4.9 % ; P = .002 ) . The bupropion rate was 6.3 % ( P = .60 vs placebo ) . Discontinuation owing to treatment-emergent adverse events was 15.9 % for bupropion , 11.2 % to 14.3 % for varenicline , and 9.8 % for placebo . No dose-related increases occurred in adverse events for varenicline . CONCLUSIONS Varenicline tartrate demonstrated both short-term ( 1 mg twice daily and 1 mg once daily ) and long-term efficacy ( 1 mg twice daily ) vs placebo . Varenicline was well tolerated and may provide a novel therapy to aid smoking cessation Stopping smoking is difficult even with treatment . Many patients prescribed pharmacologic treatments for smoking cessation experience side effects or lack of efficacy . We performed a pharmacogenetic study of the efficacy and tolerability of bupropion and transdermal nicotine ( TN ) , two treatments for smoking cessation . Sample s were drawn from two studies . In the first study ( Maintenance 1 , MT1 ) , 301 smokers received bupropion plus TN for 11 weeks , followed by 14 weeks of placebo or bupropion . In the second study ( MT2 ) , 276 smokers received bupropion and TN for 8 weeks . We focused on eight SNPs in the 15q24 region , which contains the genes for the nicotinic cholinergic receptor subunits CHRNA5 , CHRNA3 , and CHRNB4 , and has previously been implicated in nicotine addiction and smoking cessation . Analyses of baseline smoking quantity ( SQ ) identified an association between SQ and both the functional CHRNA5 SNP rs16969968 ( D398N ) and the CHRNA3 SNP rs1051730 ( Y215Y ) in a combined cohort containing MT1 and MT2 . An association between SQ and ethnicity was also identified in the combined cohort . Pharmacogenetic analysis showed a significant association between rs8192475 ( R37H ) in CHRNA3 and both higher craving after quitting and increased withdrawal symptoms over time in MT2 . Two markers for point prevalence abstinence , CHRNA5 SNP rs680244 and CHRNB4 SNP rs12914008 , were also identified in MT2 , with the strongest findings at week 52 . These results provide further support for the role of the CHRNA5/A3/B4 subunits in determining number of cigarettes smoked and response to smoking cessation therapy . © 2011 Wiley‐Liss , BACKGROUND This is the first study to examine predictors of successful cessation in African American ( AA ) light smokers treated within a placebo-controlled trial of bupropion . METHODS We analyzed data from a r and omized , double-blind , placebo-controlled trial of bupropion and health education for 540 African American light smokers . African American light smokers ( ≤10 cigarettes per day , cpd ) were r and omly assigned to receive 150 mg bid bupropion SR ( n=270 ) or placebo ( n=270 ) for 7weeks . All participants received health education counseling at weeks 0 , 1 , 3 , 5 and 7 . Using chi-square tests , two sample t-tests , and multiple logistic regression analyses , we examined baseline psychosocial and smoking characteristics as predictors of cotinine-verified 7-day point prevalence smoking abstinence among study participants at the end treatment ( Week 7 ) and at the end of follow-up ( Week 26 ) . RESULTS Participants who received bupropion were significantly more likely to quit smoking compared to those who received placebo ( OR=2.72 , 95 % CI=1.60 - 4.62 , P=0.0002 ) . Greater study session attendance ( OR=2.47 , 95 % CI=1.76 - 3.46 , P=0.0001 ) , and smoking non-menthol cigarettes increased the likelihood of quitting ( OR=1.84 , 95 % CI=1.01 - 3.36 , P=0.05 ) ; while longer years of smoking ( OR=0.98 , 95 % CI=0.96 - 1.00 , P=0.05 ) and higher baseline cotinine ( OR=0.97 , 95 % CI=0.95 - 0.99 , P=0.002 ) significantly reduced the odds of quitting at Week 7 . Conversely , at the end of follow-up ( Week 26 ) , treatment with bupropion vs. placebo ( OR=1.14 , 95 % CI=0.65 - 2.02 , P=0.64 ) was not significantly associated with quitting and type of cigarette smoked ( menthol vs. non-menthol ) did not appear in the final logistic regression model . Greater study session attendance ( OR=1.96 , 95 % CI=1.44 - 2.66 , P=0.0001 ) ; BMI ( OR=1.03 , 95 % CI=1.00 - 1.07 , P=0.04 ) ; and weight efficacy ( OR=1.03 , 95 % CI=1.01 - 1.05 , P=0.01 ) increased the likelihood of quitting at Week 26 . Similar to our findings at Week 7 , longer years of smoking ( OR=0.96 , 95 % CI=0.94 - 0.99 , P=0.01 ) and higher baseline cotinine ( OR=0.97 , 95 % CI=0.95 - 0.99 , P=0.02 ) significantly reduced the odds of quitting at Week 26 . CONCLUSIONS Baseline cotinine levels , number of years smoked and study session attendance are associated with both short- and long-term smoking cessation , while bupropion and the type of cigarette smoked were associated with quitting on short term only Background African Americans experience significant tobacco-related health disparities despite the fact that over half of African American smokers are light smokers ( use ≤10 cigarettes per day ) . African Americans have been under-represented in smoking cessation research , and few studies have evaluated treatment for light smokers . This paper describes the study design , measures , and baseline characteristics from Kick It at Swope III ( KIS-III ) , the first treatment study of bupropion for African American light smokers . Methods Five hundred forty African American light smokers were r and omly assigned to receive bupropion ( 150 mg bid ) ( n = 270 ) or placebo ( n = 270 ) for 7 weeks . All participants received written material s and health education counseling . Participants responded to survey items and provided blood sample s for evaluation of phenotype and genotype of CYP2A6 and CYP2B6 enzymes involved in nicotine and bupropion metabolism . Primary outcome was cotinine-verified 7-day point prevalence smoking abstinence at Week 26 follow-up . Results Of 2,628 individuals screened , 540 were eligible , consented , and r and omized to treatment . Participants had a mean age of 46.5 years and 66.1 % were women . Participants smoked an average of 8.0 cigarettes per day , had a mean exhaled carbon monoxide of 16.4ppm ( range 1 - 55 ) and a mean serum cotinine of 275.8ng/ml . The mean Fagerström Test for Nicotine Dependence was 3.2 , and 72.2 % of participants smoked within 30 minutes of waking . The average number of quit attempts in the past year was 3.7 and 24.2 % reported using pharmacotherapy in their most recent quit attempt . Motivation and confidence to quit were high . Conclusion KIS-III is the first study design ed to examine both nicotine and bupropion metabolism , evaluating CYP2A6 and CYP2B6 phenotype and genotype in conjunction with psychosocial factors , in the context of treatment of African American light smokers . Of 1629 smokers screened for study participation , only 18 ( 1.1 % ) were ineligible to participate in the study because they refused blood draws , demonstrating the feasibility of recruiting and enrolling African American light smokers into a clinical treatment trial involving biological data collection and genetic analyses . Future evaluation of individual factors associated with treatment outcome will contribute to advancing tailored tobacco use treatment with the goal of enhancing treatment and reducing health disparities for African American light smokers . Trial Registration Clinical Trials.gov : We conducted gender-stratified analyses on a systems-based c and i date gene study of 53 regions involved in nicotinic response and the brain — reward pathway in two r and omized clinical trials of smoking cessation treatments ( placebo , bupropion , transdermal and nasal spray nicotine replacement therapy ) . We adjusted P-values for multiple correlated tests , and used a Bonferroni-corrected α-level of 5 × 10−4 to determine system-wide significance . Four single-nucleotide polymorphisms ( rs12021667 , rs12027267 , rs6702335 , rs12039988 ; r2>0.98 ) in erythrocyte membrane protein b and 4.1 ( EPB41 ) had a significant male-specific marginal association with smoking abstinence ( odds ratio (OR)=0.5 ; 95 % confidence interval ( CI ) : 0.3–0.6 ) at end of treatment ( adjusted P<6 × 10−5 ) . rs806365 in cannabinoid receptor 1 ( CNR1 ) had a significant male-specific gene – treatment interaction at 6-month follow-up ( adjusted P=3.9 × 10−5 ) ; within males using nasal spray , rs806365 was associated with a decrease in odds of abstinence ( OR=0.04 ; 95 % CI : 0.01–0.2 ) . While the role of CNR1 in substance abuse has been well studied , we report EPB41 for the first time in the nicotine literature BACKGROUND R and omized efficacy clinical trials conducted in research setting s may not accurately reflect the benefits of tobacco dependence treatments when used in real-world clinical setting s. Effectiveness trials ( eg , in primary care setting s ) are needed to estimate the benefits of cessation treatments in real-world use . METHODS A total of 1346 primary care patients attending routine appointments were recruited by medical assistants in 12 primary care clinics . Patients were r and omly assigned to 5 active pharmacotherapies : 3 monotherapies ( nicotine patch , nicotine lozenge , and bupropion hydrochloride sustained release [ SR ] ) and 2 combination therapies ( patch + lozenge and bupropion SR + lozenge ) . Patients were referred to a telephone quit line for cessation counseling . Primary outcomes included 7-day point prevalence abstinence at 1 week , 8 weeks , and 6 months after quitting and number of days to relapse . RESULTS Among 7128 eligible smokers ( > or = 10 cigarettes per day ) attending routine primary care appointments , 1346 ( 18.9 % ) were enrolled in the study . Six-month abstinence rates for the 5 active pharmacotherapies were the following : bupropion SR , 16.8 % ; lozenge , 19.9 % ; patch , 17.7 % ; patch + lozenge , 26.9 % ; and bupropion SR + lozenge , 29.9 % . Bupropion SR + lozenge was superior to all of the monotherapies ( odds ratio , 0.46 - 0.56 ) ; patch + lozenge was superior to patch and bupropion monotherapies ( odds ratio , 0.56 and 0.54 , respectively ) . CONCLUSIONS One in 5 smokers attending a routine primary care appointment was willing to make a serious quit attempt that included evidence -based counseling and medication . In this comparative effectiveness study of 5 tobacco dependence treatments , combination pharmacotherapy significantly increased abstinence compared with monotherapies . Provision of free cessation medications plus quit line counseling arranged in the primary care setting holds promise for assisting large numbers of smokers to quit . Trial Registration clinical trials.gov Identifier : NCT00296647 OBJECTIVE To assess the efficacy of bupropion SR on smoking abstinence using a " slips allowed " analysis . METHODS Retrospective analysis , which did not consider brief episodic " slips " as a return to regular smoking , of data from a multicenter , r and omized , doubleblind , placebo-controlled relapse prevention study . RESULTS Using a slips-allowed analysis , median time to relapse on bupropion SR was 65 weeks versus 30 weeks on placebo . This is compared to 32 and 20 weeks , respectively , using a traditional analysis not allowing for slips . CONCLUSION Bupropion SR is efficacious for the prevention of smoking relapse . A slips-allowed analysis may provide a more clinical ly relevant assessment of efficacy AIM The study aim ed to test simultaneously our underst and ing of the effects of bupropion sustained-release ( SR ) treatment on putative mediators and our underst and ing of determinants of post-quit abstinence , including withdrawal distress , cigarette craving , positive affect and subjective reactions to cigarettes smoked during a lapse . The specificity of bupropion SR effects was also tested in exploratory analyses . DESIGN Data from a r and omized , placebo-controlled clinical trial of bupropion SR were su bmi tted to mediation analyses . SETTING Center for Tobacco Research and Intervention , Madison , WI , USA . PARTICIPANTS A total of 403 adult , daily smokers without contraindications to bupropion SR use . INTERVENTION Participants were assigned r and omly to receive a 9-week course of bupropion SR or placebo pill and to receive eight brief individual counseling sessions or no counseling . MEASUREMENTS Ecological momentary assessment ratings of smoking behavior and putative mediators were collected pre- and post-quit . FINDINGS Results of structural equation and hierarchical linear models did not support the hypothesis that bupropion SR treatment improves short-term abstinence by reducing withdrawal distress or affecting the subjective effects of a lapse cigarette , but provided partial support for mediation by cigarette craving reduction and enhanced positive affect . Bupropion SR effects on point-prevalence abstinence at 1 month post-quit were also mediated partially by enhanced motivation to quit and self-efficacy . CONCLUSIONS Results provided some support for models of bupropion SR treatment and relapse and suggested that motivational processes may partially account for bupropion SR efficacy 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 Background In many low- and middle-income countries , where tobacco use is common , tuberculosis is also a major problem . Tobacco use increases the risk of developing tuberculosis , secondary mortality , poor treatment compliance and relapses . In countries with TB epidemic , even a modest relative risk leads to a significant attributable risk . Treating tobacco dependence , therefore , is likely to have benefits for controlling tuberculosis in addition to reducing the non-communicable disease burden associated with smoking . In poorly re source d health systems which face a dual burden of disease secondary to tuberculosis and tobacco , an integrated approach to tackle tobacco dependence in TB control could be economically desirable . During TB screening , health professionals come across large numbers of patients with respiratory symptoms , a significant proportion of which are likely to be tobacco users . These clinical encounters , considered to be " teachable moments " , provide a window of opportunity to offer treatment for tobacco dependence . Methods / Design We aim to develop and trial a complex intervention to reduce tobacco dependence among TB suspects based on the WHO ' five steps to quit ' model . This model relies on assessing personal motivation to quit tobacco use and uses it as the basis for assessing suitability for the different therapeutic options for tobacco dependence . We will use the Medical Research Council framework approach for evaluating complex interventions to : ( a ) design an evidence -based treatment package ( likely to consist of training material s for health professionals and education tools for patients ) ; ( b ) pilot the package to determine the delivery modalities in TB programme ( c ) assess the incremental cost-effectiveness of the package compared to usual care using a cluster RCT design ; ( d ) to determine barriers and drivers to the provision of treatment of tobacco dependence within TB programmes ; and ( e ) support long term implementation . The main outcomes to assess the effectiveness would be point abstinence at 4 weeks and continuous abstinence up to 6 months . Discussion This work will be carried out in Pakistan and is expected to have relevance for other low and middle income countries with high tobacco use and TB incidence . This will enhance our knowledge of the cost-effectiveness of treating tobacco dependence in patients suspected of TB.Trial Registration Trial Registration Number : IS RCT 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 BACKGROUND Although smoking cessation is essential for prevention of secondary cardiovascular disease ( CVD ) , many smokers do not stop smoking after hospitalization . Mild depressive symptoms are common during hospitalization for CVD . We hypothesized that depressive symptoms measured during hospitalization for acute CVD would predict return to smoking after discharge from the hospital . METHODS This was a planned secondary analysis of data from a placebo-controlled , double-blind , r and omized trial of bupropion hydrochloride therapy in 245 smokers hospitalized for acute CVD . All subjects received smoking counseling in the hospital and for 12 weeks after discharge . Depressive symptoms were measured during hospitalization with the Beck Depression Inventory ( BDI ) , and smoking cessation was biochemically vali date d at 2-week , 12-week , and 1-year follow-up . The effect of depressive symptoms on smoking cessation was assessed using multiple logistic regression and survival analyses . RESULTS Twenty-two percent of smokers had moderate to severe depressive symptoms ( BDI > or= 16 ) during hospitalization . These smokers were more likely to resume smoking by 4 weeks after discharge ( P= .007 ; incidence rate ratio , 2.40 ; 95 % confidence interval , 1.48 - 3.78 ) than were smokers with lower BDI scores . Smokers with low BDI scores were more likely to remain abstinent than were those with high BDI scores at 3-month follow-up ( 37 % vs 15 % ; adjusted odds ratio , 3.02 ; 95 % confidence interval , 1.28 - 7.09 ) and 1-year follow-up ( 27 % vs 10 % ; adjusted odds ratio , 3.77 ; 95 % confidence interval , 1.31 - 10.82 ) . We estimate that 27 % of the effect of the BDI score on smoking cessation was mediated by nicotine withdrawal symptoms . CONCLUSIONS Moderate to severe depressive symptoms during hospitalization for acute CVD are independently associated with rapid relapse to smoking after discharge and lower rates of smoking cessation at long-term follow-up . The relationship was mediated in part by the stronger nicotine withdrawal symptoms experienced by smokers with higher depressive symptoms INTRODUCTION Bupropion is a first-line pharmacological aid for smoking cessation ; however , no clinical trials have been conducted in a Chinese population . METHODS We enrolled 248 smokers in a hospital-based , r and omized , smoking cessation trial conducted at four outpatient centers in Beijing . A total of 123 participants received an 8-week course of sustained-release bupropion ( Bup-SR ) and 125 participants received 8 weeks of placebo . All participants received brief education and counseling on smoking cessation . We determined rates of abstinence and smoking reduction based on chemical verification and self-report at 8 and 12 weeks . RESULTS At the end of the medication treatment ( 8 weeks ) and at the end of the trial ( 12 weeks ) , the abstinence rates for Bup-SR were 29.3 % and 39.8 % , respectively , and 10.4 % and 8.0 % for placebo , respectively ( both p < .001 ) . Bup-SR was also superior to placebo in reducing cigarettes per day and urinary cotinine levels . CONCLUSION Bup-SR is efficacious for smoking cessation in healthy Chinese patients treated in the outpatient setting . It is well tolerated with a few mild side effects Although there is a strong relationship between depression and smoking , most nicotine dependence treatment trials exclude depressed smokers . Our objective was to determine whether bupropion improves abstinence rates and abstinence-associated depressive symptoms when added to transdermal nicotine replacement therapy ( NRT ) and group cognitive behavioral therapy ( CBT ) in smokers with unipolar depressive disorder ( UDD ) . Adult smokers with current ( n = 90 ) or past ( n = 109 ) UDD were r and omly assigned to receive bupropion or placebo added to NRT and CBT for 13 weeks . In the primary analysis , with dropouts considered smokers , 36 % ( 35/97 ) of those on bupropion and 31 % ( 32/102 ) on placebo attained biochemically vali date d 7-day point prevalence abstinence at end of treatment ( not significant ) . Because of a high dropout rate ( 50 % ) and a significant difference in abstinence status at dropout by treatment group , a traditional intent-to-treat analysis with last observation carried forward imputation of abstinence status was performed . In this secondary analysis , 56 % ( 54/97 ) of those on bupropion and 41 % ( 42/102 ) on placebo met criteria for abstinence at end of trial , & khgr;2 = 4.18 , P = 0.04 . Nicotine replacement therapy usage and absence of a comorbid anxiety disorder predicted abstinence . Abstinence was associated with increased depressive symptoms , regardless of bupropion treatment . Thus , in the primary analysis , bupropion neither increased the efficacy of intensive group CBT and NRT for smoking cessation in smokers with UDD nor prevented abstinence-associated depressive symptoms . Bupropion seemed to provide an advantage for smoking cessation for those who remained in the trial . The dropout rate was high and was characterized by a higher prevalence of current comorbid anxiety disorder . Given the high abstinence rate achieved with CBT plus NRT , a ceiling effect related to the high level of intervention received by all subjects may have prevented an adequate test of bupropion BACKGROUND This prospect i ve 105-site study was conducted to determine the rate of seizures and other serious adverse experiences associated with the therapeutic use of the sustained-release formulation of bupropion ( bupropion SR ) . METHOD 3100 patients with a DSM-III-R diagnosis of depression without a current or past diagnosis of an eating disorder and with no personal or family history of seizure disorders were treated for up to 8 weeks with bupropion SR in an open-label study . Dosing was initiated at 50 mg b.i.d . and increased to a maximum of 150 mg b.i.d . unless not tolerated . Patients had the option to continue treatment with bupropion SR ( 50 mg b.i.d . to 150 mg b.i.d . ) in a continuation phase lasting up to 1 year . During the acute and continuation phases , patients were evaluated for the occurrence of seizures and other serious adverse experiences . Clinical response to and tolerability of bupropion SR were also evaluated . RESULTS Three patients each experienced a seizure associated with the therapeutic use of bupropion SR during the acute and continuation phases combined . The observed seizure rate during the 8-week acute phase was 2 seizures in 3094 evaluable patients , or 0.06 % . The observed seizure rate for the acute and continuation phases combined was 3 seizures in 3094 patients , or 0.10 % . Survival analysis yielded a cumulative seizure rate of 0.08 % for the acute phase and 0.15 % for both phases combined . Two patients who intentionally overdosed with bupropion SR also experienced seizures ; however , these events were not included in calculations of the overall seizure rate . Therapeutic doses of bupropion SR were well tolerated and clinical ly efficacious . CONCLUSION The therapeutic use of bupropion SR at total daily doses up to 300 mg/day in depressed patients without predisposition to seizures is associated with a seizure rate that is well within the range observed with other marketed antidepressants BACKGROUND Most ( > 50 % ) smokers who attempt to stop smoking relapse within the first year of abstinence . The effect of continued use of pharmacotherapy for smoking cessation on relapse rates is unknown . Bupropion sustained-release ( SR ) is the first non-nicotine-based therapy that is effective for achieving abstinence from smoking . OBJECTIVE This analysis explored the factors involved in relapse to smoking in patients who had successfully stopped smoking using bupropion SR . These patients were participants in a double-blind , placebo-controlled trial of bupropion SR for the prevention of relapse to smoking . METHODS Participants who had stopped smoking with 7 weeks of open-label bupropion SR were r and omly assigned to receive double-blind treatment with either bupropion SR or placebo for 45 weeks . The primary efficacy outcome of the main study was the rate of relapse to smoking . The analyses presented here examine the levels of reported cigarette craving and , in those participants who returned to smoking , the reasons associated with relapse , using patient-completed question naires . RESULTS Craving was cited most frequently as a factor contributing to relapse in those participants receiving placebo ( cited by 49.2 % of relapsers ) but significantly less frequently by participants receiving bupropion SR ( cited by 22.4 % of relapsers ) ( P < 0.05 ) . Results from patients ' diaries showed no differences between bupropion SR and placebo in terms of " craving in the past 24 hours " but significantly lower scores for " craving right now " for bupropion SR at weeks 11 and 12 ( P < 0.05 ) . Results at scheduled visits showed that " craving in the past 24 hours " was significantly less with bupropion SR compared with placebo at weeks 12 , 20 , and 48 , and " craving right now " was significantly less with bupropion SR compared with placebo at weeks 12 , 16 , 20 , 24 , 48 , and 52 ( P < 0.05 ) . CONCLUSIONS Craving continues to be a significant concern for individuals even after they have successfully stopped smoking . Bupropion SR appears to reduce reported cravings , which may contribute to the overall reduction in the rate of relapse observed with this pharmacotherapy Background African Americans are at risk of inadequate adherence to smoking cessation treatment , yet little is known about what leads to treatment discontinuation . Purpose The purpose of this study was to examine the factors associated with discontinuation of treatment in African American light smokers ( ≤10 cigarettes per day ) . Methods Bupropion plasma levels and counseling attendance were measured among 540 African American light smokers in a placebo-controlled r and omized trial of bupropion . Results By week 3 , 28.0 % of subjects in the bupropion arm had discontinued bupropion , and only moderate associations were found between the plasma levels and self-reported bupropion use ( rs = 0.38 ) . By week 16 , 36.9 % of all subjects had discontinued counseling . Males had greater odds of discontinuing medication ( OR = 2.02 , 95 % CI = 1.10–3.71 , p = 0.02 ) , and older adults had lower odds of discontinuing counseling ( OR = 0.96 , 95 % CI = 0.94–0.97 , p < 0.0001 ) . Conclusions Bupropion and smoking cessation counseling are underutilized even when provided within the context of a r and omized trial . Future research is needed to examine strategies for improving treatment utilization among African American smokers . Trial Registration No. NCT00666978 ( www . clinical trials.gov ) Background There has been limited research addressing changes in subjective well-being as a result of quitting smoking . Purpose The purpose of this study was to use longitudinal data to determine the relation between smoking cessation and subjective measures of well-being , including global quality of life ( QOL ) , health-related QOL ( HR-QOL ) , affect , relationship satisfaction , and stressor occurrence . Methods As part of a r and omized , placebo-controlled smoking cessation trial , 1,504 participants ( 58.2 % women , 83.9 % white ) completed assessment s and had their smoking status biochemically confirmed at baseline and years 1 and 3 post-quit . Results Compared with continuing smokers , quitters showed improved global QOL , HR-QOL , and affect at years 1 and 3 and fewer stressors by year 3 . Smoking status did not influence marital relationship satisfaction . Conclusions Successful quitters , in contrast to continuing smokers , reported improved subjective well-being , which could be used to motivate quit attempts by individuals with concerns about what life will be like without cigarettes We tested whether 14 wk of dexfenfluramine ( 30 mg ) or fluoxetine ( 40 mg ) treatment would prevent weight gain after subjects quit smoking . Normal-weight women ( n = 144 ) were r and omly assigned to drug or placebo on a double-blind basis for 2 wk before quitting smoking and 12 wk thereafter . The fluoxetine group had more dropouts ( 28/49 , 57.1 % ) than the dexfenfluramine group ( 17/47 , 36.2 % ) , with an intermediate number of dropouts from the placebo group ( 21/48 , 43.8 % ) . All groups gained weight during treatment , but their amount and pattern of weight gain differed . In the first month after quitting smoking , the placebo group gained more weight than either the dexfenfluramine or fluoxetine group ( P < 0.05 ) . By 2 mo postcessation , dexfenfluramine still suppressed weight gain in comparison with placebo ( P < 0.05 ) ; weight gain with fluoxetine was not differentiable from either dexfenfluramine or placebo . By 3 mo postcessation , the dexfenfluramine group had gained 1.0 + /- 0.7 kg , significantly less than either the placebo ( 3.5 + /- 0.7 kg ) or fluoxetine ( 2.7 + /- 0.5 kg ) groups . Three months after drug discontinuation , formerly medicated , but not placebo patients , showed additional weight gain , eliminating differences between groups . Results indicate that weight gain , an adverse accompaniment of smoking cessation , can be minimized to some degree by serotoninergic drugs , although only for the duration of drug treatment 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 INTRODUCTION DRD4 Exon III Variable Number of T and em Repeat ( VNTR ) variation was found to interact with bupropion to influence prospect i ve smoking abstinence , in a recently published longitudinal analyses of N = 331 individuals from a r and omized double-blind placebo-controlled trial of bupropion and intensive cognitive-behavioral mood management therapy . METHODS We used univariate , multivariate , and longitudinal logistic regression to evaluate gene , treatment , time , and interaction effects on point prevalence and continuous abstinence at end of treatment , 6 months , and 12 months , respectively , in N = 416 European ancestry participants in a double-blind pharmacogenetic efficacy trial r and omizing participants to active or placebo bupropion . Participants received 10 weeks of pharmacotherapy and 7 sessions of behavioral therapy , with a target quit date 2 weeks after initiating both therapies . VNTR genotypes were coded with the long allele dominant result ing in 4 analysis categories . Covariates included demographics , dependence measures , depressive symptoms , and genetic ancestry . We also performed genotype-stratified secondary analyses . RESULTS We observed significant effects of time in longitudinal analyses of both abstinence outcomes , of treatment in individuals with VNTR long allele genotypes for both abstinence outcomes , and of covariates in some analyses . We observed non-significantly larger differences in active versus placebo effect sizes in individuals with VNTR long allele genotypes than in individuals without the VNTR long allele , in the directions previously reported . CONCLUSIONS VNTR by treatment interaction differences between these and previous analyses may be attributable to insufficient size of the replication sample . Analyses of multiple r and omized clinical trials will enable identification and validation of factors mediating treatment response OBJECTIVE The present study sought to better underst and the relationships among smoking history , motivation to change , and smoking cessation outcomes in people with schizophrenia who smoke . METHOD We examined smoking and quit history , negative consequences due to smoking , readiness to change , smoking temptation , and confidence to quit in a sample of people diagnosed with schizophrenia or schizoaffective disorder according to DSM-IV criteria who were participating in a larger r and omized trial of bupropion SR and a psychoeducational intervention for smoking cessation . Data were collected from June 2003 to May 2005 . RESULTS At baseline , participants reported high levels of nicotine dependence and daily smoking , as well as multiple recent and lifetime quit attempts that were generally brief in nature . Participants were most concerned about the health effects of smoking and endorsed reasons for smoking related to coping with negative affect and boredom . Most participants reported wanting to quit smoking , but the sample generally reported low levels of confidence in their ability to quit . During the course of participation in the intervention , self-efficacy to quit increased while temptation to smoke decreased ; however readiness to quit remained unchanged . CONCLUSION Smoking cessation programs for people with schizophrenia should focus on teaching coping skills for negative affect , boredom , and specific " high risk situations " for smoking in addition to education , medication , or nicotine replacement therapy . Further , cessation efforts may benefit from directly addressing low self-efficacy for quitting , rather than readiness for change alone , among people with schizophrenia AIMS To assess the relations of menthol cigarette use with measures of cessation success in a large comparative effectiveness trial ( CET ) . DESIGN Participants were r and omized to one of six medication treatment conditions in a r and omized double-blind , placebo-controlled clinical trial . All participants received six individual counseling sessions . SETTING Community-based smokers in two communities in Wisconsin , USA . PARTICIPANTS A total of 1504 adult smokers who smoked at least 10 cigarettes per day during the past 6 months and reported being motivated to quit smoking . The analysis sample comprised 1439 participants : 814 white non-menthol smokers , 439 white menthol smokers and 186 African American ( AA ) menthol smokers . There were too few AA non-menthol smokers ( n = 16 ) to be included in the analyses . INTERVENTIONS Nicotine lozenge , nicotine patch , bupropion sustained release , nicotine patch + nicotine lozenge , bupropion + nicotine lozenge and placebo . MEASUREMENTS Biochemically confirmed 7-day point-prevalence abstinence assessed at 4 , 8 and 26 weeks post-quit . FINDINGS In longitudinal abstinence analyses ( generalized estimating equations ) controlling for cessation treatment , menthol smoking was associated with reduced likelihood of smoking cessation success relative to non-menthol smoking [ model-based estimates of abstinence = 31 versus 38 % , respectively ; odds ratio ( OR ) = 0.71 , 95 % confidence interval ( CI ) = 0.59 , 0.86 ] . In addition , among menthol smokers , AA women were at especially high risk of cessation failure relative to white women ( estimated abstinence = 17 versus 35 % , respectively ; OR = 2.63 , 95 % CI = 1.75 , 3.96 ; estimated abstinence rates for AA males and white males were both 30 % , OR = 1.06 , 95 % CI = 0.60 , 1.66 ) . CONCLUSION In the United States , smoking menthol cigarettes appears to be associated with reduced cessation success compared with non-menthol smoking , especially in African American females Background : Smoking rates are high in indigenous population s and contribute to their poor health . In New Zeal and the indigenous Maori population has a high rate of smoking , with around 50 % of adults being smokers compared with 20 % of the adult European population . A study was undertaken to determine whether bupropion is effective in the treatment of smoking cessation in the indigenous Maori population in New Zeal and . Methods : A r and omised , placebo controlled , double blind , parallel group study was performed in 134 Maori smokers aged 16–70 years who smoked more than 10 cigarettes per day . The main outcome measures were continued abstinence from smoking at 3 and 12 months . Results : At each time point continued abstinence was better for the subjects allocated to bupropion , with a risk ratio for abstinence over all time points of 2.44 ( 95 % CI 1.22 to 4.88 ) . The rates of continued abstinence in the bupropion and placebo groups at 3 months were 44.3 % and 17.4 % , respectively , with a risk ratio of 2.54 ( 95 % CI 1.30 to 5.00 ) . The corresponding figures at 12 months were 21.6 % and 10.9 % , respectively , with a risk ratio of 1.99 ( 95 % CI 0.79 to 5.00 ) . Conclusion : Bupropion is an effective treatment for smoking cessation in the indigenous Maori population in New Zeal and BACKGROUND Schizophrenic patients have high rates of cigarette smoking compared with the general population . We compared sustained-release ( SR ) bupropion with placebo for smoking cessation in patients with schizophrenic disorders . We also examined how antipsychotic class predicts smoking cessation outcomes with bupropion . METHODS Thirty-two subjects meeting DSM-IV criteria for schizophrenia or schizoaffective disorder and nicotine dependence were r and omized to bupropion SR ( BUP , 300 mg/day ) or placebo ( PLA ) . Outcomes included treatment retention , smoking abstinence rates , expired breath carbon monoxide ( CO ) levels , psychotic symptoms , and medication side effects . RESULTS Bupropion significantly increased trial endpoint 7-day point prevalence smoking abstinence rates compared with placebo [ BUP , 8/16 ( 50.0 % ) , PLA , 2/16 ( 12.5 % ) ; chi(2 ) = 5.24 , df = 1 , p < .05 ] , and reduced CO levels during the trial [ Medication x Time interaction ; Z = 3.09 , p < .01 ] . Positive schizophrenia symptoms were not altered by BUP , but negative symptoms were significantly reduced . Atypical antipsychotic drug treatment enhanced smoking cessation responses to BUP . Major side effects were dry mouth , gastrointestinal symptoms , headache , and insomnia . CONCLUSIONS Our results suggest that 1 ) BUP enhances smoking abstinence rates compared with PLA in nicotine-dependent schizophrenic smokers ; 2 ) BUP is well-tolerated and safe for use in these patients ; and 3 ) atypical antipsychotics may enhance smoking cessation outcomes with BUP Smoking cessation treatment is now integrated into many health-care systems and a major research effort is under way to improve current success rates . Until now results from r and omized clinical trials have been reported in many different ways , leading to problems of interpretation . We propose six st and ard criteria comprising the ' Russell St and ard ' ( RS ) . These criteria are applicable to trials of cessation aids where participants have a defined target quit date and there is face-to-face contact with research ers or clinic staff , as follows . ( 1 ) Follow-up for 6 months ( RS6 ) or 12 months ( RS12 ) from the target quit date or the end of a predefined ' grace period ' ; ( 2 ) self-report of smoking abstinence over the whole follow-up period allowing up to five cigarettes in total ; ( 3 ) biochemical verification of abstinence at least at the 6-month or 12-month follow-up point ; ( 4 ) use of an ' intention-to-treat ' approach in which data from all r and omized smokers are included in the analysis unless they have died or moved to an untraceable address ( participants who are included in the analysis are counted as smokers if their smoking status at the final follow-up can not be determined ) ; ( 5 ) following-up ' protocol violators ' and using their true smoking status in the analysis ; and ( 6 ) collecting follow-up data blind to smokers ' allocation to trial group . We believe that these criteria provide the best compromise between practicability and surrogacy for long-term cessation and will enable meaningful comparison between studies . There may be good reasons why other outcome criteria would also be reported , and studies that involve interventions with special groups or where there is no design ated target quit date or face to face contact would need to adapt these criteria accordingly BACKGROUND St John 's wort is an effective antidepressant that can reduce tobacco withdrawal symptoms , but it is not known whether it assists cessation . Chromium assists weight loss and might limit post cessation weight gain . METHODS In a factorial design , we r and omised smokers stopping smoking to 900 mg St John 's wort ( SJW ) active or placebo and also r and omised them to 400 microm chromium or placebo daily . Treatment started 2 weeks prior to quit day and continued for 14 weeks . Participants and research ers were blind to treatment allocation . All participants received weekly behavioural support . The primary endpoints were biochemically confirmed prolonged abstinence and mean weight gain in abstinent smokers 4 weeks after quitting . RESULTS 6/71 ( 8.5 % ) participants on active SJW and 9/72 ( 12.5 % ) on placebo achieved prolonged abstinence at 4 weeks , an odds ratio ( OR ) ( 95 % confidence interval ) of 0.65 ( 0.22 - 1.92 ) . At 6 months , 3 ( 4.2 % ) SJW active and 6 ( 8.3 % ) SJW placebo participants were still abstinent , an OR of 0.49 ( 0.12 - 2.02 ) . Among these participants , the mean difference in weight gain between active chromium and placebo was -0.8 1 kg ( -3.79 to 2.18 ) at 4 weeks and -3.88 kg ( -12.13 to 4.38 ) at 6 months . CONCLUSIONS Taking together the absolute quit rates , the small difference between active and placebo , and lack of effects on withdrawal shows that SJW is ineffective for smoking cessation . Insufficient people stopped smoking to properly test the efficacy of chromium in preventing weight gain , but the point estimate indicates a potentially worthwhile benefit OBJECTIVE To evaluate two counseling programs in general practice to help smokers with chronic obstructive pulmonary disease ( COPD ) to quit smoking . METHODS Cluster r and omized controlled trial including 68 general practice s ( 667 patients ) using a r and omly assigned intervention program with counseling and advice about nicotine replacement therapy ( and additional bupropion-SR in one of the programs ) or usual care . Usual care consisted of periodic regular check-ups and COPD information . The main outcome measure was biochemically verified point prevalence at 12 months . RESULTS The two intervention groups were treated as one in the analysis because they were equally effective . The intervention result ed in a significantly self-reported higher success rate ( 14.5 % ) compared to usual care ( 7.4 % ) ; odds ratio=2.1 , 95 % confidence interval=1.1 - 4.1 . Biochemically verified quit rates were 7.5 % ( intervention ) and 3.4 % ( usual care ) ; odds ratio=2.3 , 95 % confidence interval=0.9 - 6.0 . CONCLUSION The program doubled the cessation rates ( statistically nonsignificant ) . Too few participants used the additional bupropion-SR to prove its effectiveness . PRACTICE IMPLICATION S The protocol s can be used for COPD patients in general practice , but expectations should be modest . If quitting is unsuccessful , a stepped care approach should be considered BACKGROUND Bupropion hydrochloride is recommended for smoking cessation ; however , there have been relatively few clinical trials examining its efficacy . METHODS A total of 244 current smokers were enrolled in an outpatient r and omized blinded smoking cessation trial conducted at the San Francisco Veterans Affairs Medical Center , San Francisco , Calif. Of the 244 participants , 121 received a 7-week course of bupropion and 123 received placebo . All participants received 2 months of transdermal nicotine replacement therapy and 3 months of cognitive-behavioral counseling . We determined on-medication treatment , end-of-medication treatment , 3-month , 6-month , and 1-year quit rates . RESULTS During treatment with bupropion vs placebo , there was a trend toward increased quit rates among participants r and omized to bupropion ; the self-reported end-of-medication treatment quit rates were 64 % for the bupropion group vs 57 % for the placebo group ( P = .23 ) . The trend favoring bupropion persisted at 3 months of follow-up ( P = .12 ) but was not apparent at 6 months and 1 year of follow-up ( both P>.78 ) . The 12-month quit rates , vali date d by either saliva cotinine or spousal proxy , were 22 % in the bupropion group and 28 % in the placebo group ( P = .31 ) . Based on biochemical validation , 19 % of the bupropion group vs 24 % of the placebo group had quit smoking by 1 year ( P = .36 ) . CONCLUSIONS In this r and omized blinded trial of mostly veteran participants , the addition of a brief 7-week bupropion trial to treatment with nicotine replacement therapy and counseling did not significantly increase smoking cessation rates This study used ecological momentary assessment data from adult daily smokers attempting to quit smoking to assess relations between exposure to context ual risk factors and cessation failure , latency to a first smoking lapse , or progression from lapse to relapse ( smoking 7 days in a row ) . Participants were adult , daily smokers enrolled in a r and omized controlled clinical trial of bupropion SR and individual counseling who were followed to 1 year postquit . Participants reported exposure to high-risk context s and behaviors , including being where cigarettes were available or smoking was permitted , being around others smoking in prospect i ve , real-time assessment for 2 weeks pre- and 4 weeks postquit . Results showed that greater exposure to context ual risk factors during the prequit did not predict cessation failure . However , Cox regression survival analyses revealed that spending a greater proportion of time where cigarettes were easily available following at least 1 day of abstinence predicted shorter latency to a first lapse , even after controlling for baseline risk factors such as gender , nicotine dependence , depressive symptoms , and living with a smoker . Greater cigarette availability following a lapse was not associated with progression from lapse to relapse with or without baseline risk factors in the model . This suggests that postquit environmental risk factors , such as cigarette availability , increase lapse risk , and stable risk factors , such as living with smokers and higher baseline carbon monoxide level or depressive symptoms , remain potent predictors of progression to relapse . Real-time context ual risk assessment s postquit predict lapse above and beyond stable , baseline risk factors . ( PsycINFO Data base OBJECTIVE To compare bupropion to placebo for reducing methamphetamine ( MA ) use , increasing retention , and reducing the severity of depressive symptoms and MA-cravings . A secondary objective compared bupropion to placebo for reducing cigarette smoking among MA dependent participants . METHODS Following a 2-week , non-medication baseline screening period , 73 treatment-seeking MA dependent participants were r and omly assigned to bupropion sustained release ( 150 mg twice daily ; N=36 ) or placebo ( twice daily ; N=37 ) for 12-weeks under double-blind conditions . Participants attended clinic thrice weekly to provide urine sample s analyzed for MA-metabolite , to complete research measures and assessment s , and to receive contingency management and weekly cognitive behavioral therapy sessions . RESULTS There were no statistically significant effects for bupropion relative to placebo on MA use verified by urine drug screens , for reducing the severity of depressive symptoms or MA-cravings , or on study retention . In a post hoc analysis , there was a statistically significant effect of bupropion treatment on MA use among participants with lighter ( 0 - 2 MA-positive urines ) , but not heavier ( 3 - 6 MA-positive urines ) MA use during baseline ( OR=2.81 , 95 % CI=1.61 - 4.93 , p<0.001 for MA-free week with bupropion among light users ) . Bupropion treatment was also associated with significantly reduced cigarette smoking , by almost five cigarettes per day ( p=0.0002 ) . CONCLUSION Bupropion was no more effective than placebo in reducing MA use in planned analyses , though bupropion did reduce cigarette smoking . Post hoc findings of an effect for bupropion among baseline light , but not heavy , MA users suggests further evaluation of bupropion for light-MA users is warranted Bupropion is an efficacious non-nicotine medication for smoking cessation ; however , its cessation-mediating mechanism is unclear . This r and omized , placebo-controlled trial examined the effect of bupropion SR ( 300 mg/day for 6 weeks ) on plasma cotinine and on the subjective effects of smoking in 24 current daily smokers who were not trying to quit or reduce smoking . Subjective effects of smoking , as well as cue-elicited responses were assessed at bi-weekly experimental sessions using vali date d scales . Several indices of cigarette consumption were measured . Plasma cotinine decreased from 280 ( + /-133 ) microg/l at baseline to 205 ( + /-108 ) microg/l at end of treatment in the bupropion group ( p=0.036 ) , but no significant change was found in the placebo group . Daily cigarette count and puff topography did not significantly change in either group . In contrast to placebo , bupropion increased post-smoking satiety ( p=0.045 ) . Both groups reported higher craving ( p=0.025 ) and withdrawal ( p=0.014 ) after exposure to smoking-related pictures , compared to neutral pictures . This biased reactivity was not significantly affected by treatment condition ( p>0.1 ) . Therefore , bupropion does not appear to impact the smokers ' response to conditioned smoking-related cues but influences the unconditioned subjective effects of smoking in unmotivated smokers . This study is among the first to systematic ally investigate the effect of chronic bupropion administration , free from the confounding effect of the smoker 's motivation to quit smoking This r and omized , double-blinded , placebo-controlled trial examined genetic influences on treatment response to sustained-release bupropion for smoking cessation . Smokers of European ancestry ( N = 291 ) , who were r and omized to receive bupropion or placebo ( 12 weeks ) plus counseling , were genotyped for the dopamine D2 receptor ( DRD2-Taq1A ) , dopamine transporter ( SLC6A3 3 ' VNTR ) , and cytochrome P450 2B6 ( CYP2B6 1459 CT ) polymorphisms . Main outcome measures were cotinine-verified point prevalence of abstinence at end of treatment and at 2- , 6- , and 12-month follow-ups post quit date . Using generalized estimating equations , we found that bupropion , compared with placebo , was associated with significantly greater odds of abstinence at all time points ( all p values<.01 ) . We found a significant DRD2 x bupropion interaction ( B = 1.49 , SE = 0.59 , p = .012 ) [ corrected ] and a three-way DRD2 x bupropion x craving interaction on 6-month smoking cessation outcomes ( B = -0.45 , SE = 0.22 , p = .038 ) , such that smokers with the A2/A2 genotype demonstrated the greatest craving reduction and the highest abstinence rates with bupropion . Furthermore , there was a significant DRD2 x CYP2B6 interaction ( B = 1.43 , SE = 0.56 , p = .01 ) , such that individuals with the DRD2-Taq1 A2/A2 genotype demonstrated a higher odds of abstinence only if they possessed the CYP2B6 1459 T/T or C/T genotype . Because the sample size of this study was modest for pharmacogenetic investigations , the results should be interpreted with caution . Although these results require replication , the data suggest preliminarily that the DRD2-Taq1A polymorphism may influence treatment response to bupropion for smoking cessation and , further , that exploration of gene x gene and gene x craving interactions in future , larger studies may provide mechanistic insights into the complex pharmacodynamics of bupropion Few pharmacological therapies have been shown to increase abstinence rates among spit tobacco ( ST ) users . Bupropion has been shown to be effective in increasing abstinence rates among smokers but has not been studied in ST users . Sixty-eight adult ( aged > or = 18 years old ) regular users of ST who were motivated to stop using ST were enrolled in a r and omized , double-blind , placebo-controlled pilot study of bupropion sustained release ( SR ) or placebo for 12 weeks . The primary endpoint was 1-week , biochemically confirmed point-prevalence tobacco abstinence rate at the end of treatment ( week 12 ) . Nicotine withdrawal symptoms and weight change were assessed . At the end of 12 weeks of therapy , the point-prevalence tobacco abstinence rate was 44 % in the bupropion group and 26 % in the placebo group ( p = 0.064 ) . At 24 weeks following initiation of medication , the point-prevalence abstinence rate was 29 % for both groups . After 7 weeks of medication , subjects on bupropion reported significantly less ( p < or = 0.034 ) nicotine withdrawal than placebo . The mean weight change from baseline to end of treatment was + 0.7 + /- 1.9 kg for bupropion and + 4.4 + /- 2.4 kg for placebo ( p = 0.03 ) . The 6-month weight change for continuously abstinent subjects was 3.4 + /- 3.6 kg in the bupropion group and 6.2 + /- 5.0 kg in the placebo group ( p = 0.49 ) . Bupropion may increase abstinence rates in ST users and appears to attenuate weight gain during ST abstinence . Larger r and omized , controlled trials of bupropion for ST users are needed In a double-blind placebo-controlled trial , we evaluated the efficacy of the combination of sertraline and buspirone plus cognitive-behavioral treatment to promote tobacco abstinence in individuals referred to a chemical dependency clinic . Ninety eight individuals 18–65 years of age were r and omized to placebo or sertraline 25 mg/day for 2 days , followed by 50 mg from day 3 to 90 , and buspirone 5 mg three times a day for 7 days , and 10 mg from day 8 to 90 . The rate of continuous abstinence at the 26th week of follow-up , informed by the patient , was 43.5 % in the active treatment group and 17.3 % in the control group ( p = 0.01 ) . The odds ratio for continuous abstinence for the intervention group was 4.74 ( 95 % CI 1.50–14.55 ) ( adjusted for smoker households and number of cognitive sessions ) . Nicotine withdrawal symptoms were common in both groups ( 98.7 % vs. 95.5 % p = 0.37 ) . The combination of sertraline and buspirone with cognitive-behavioral therapy was more effective than placebo and cognitive-behavioral therapy to promote smoking cessation The effects of fluoxetine , a relatively selective long‐acting serotonin uptake inhibitor , on the consumption of alcoholic and nonalcoholic drinks , cigarette smoking , and body weight were assessed in 29 men who were early stage problem drinkers . After a 2‐week baseline , subjects were r and omly assigned to receive 40 mg/day fluoxetine ( n = 8) , 60 mg/day fluoxetine ( n = 11 ) , or placebo ( n = 10 ) for 4 weeks . Fluoxetine 60 mg/day decreased mean daily alcoholic drinks from ( X̄ ± SEM ) 8.3 ± 0.7 during baseline to 6.9 ± 0.7 and decreased total drinks per 14 days from 115.8 ± 9.3 to 96.5 ± 9.5 ( p < 0.01 ; 17.3 % decrease from baseline ) , with no significant increase in days of abstinence . Neither 40 mg/day fluoxetine nor placebo had effects on intake of alcohol . Fluoxetine 60 mg/day decreased total and mean daily alcoholic drinks compared with 40 mg/day fluoxetine ( ANCOVA , both p < 0.02 ) , but neither dose of fluoxetine was different from placebo . Compared with placebo , both 40 mg/day fluoxetine and 60 mg/day fluoxetine decreased the variability of the baseline to treatment changes in alcoholic drinks ( both p < 0.05 ) . Although no differences were detected between treatment groups , 60 mg/day fluoxetine increased mean daily nonalcoholic beverages from baseline ( 5.0 ± 0.4 to 5.6 ± 0.3 , p < 0.01 ) and increased daily cigarettes smoked ( from 25.1 ± 4.6 to 26.9 ± 4.5 , p < 0.05 ) , whereas no significant changes from baseline were observed with 40 mg/day fluoxetine or placebo . Body weight decreased with both 40 mg/day fluoxetine ( from 75.7 ± 4.7 kg to 73.8 ± 4.6 kg , p < 0.01 ) and 60 mg/day fluoxetine ( from 81.4 ± 2.6 kg to 79.2 ± 2.5 kg , p < 0.05 ) but not with placebo . Patterns of response varied , but decreases in alcohol consumption were not related to side effects , an alcohol‐sensitizing reaction , or changes in depression or anxiety . Our findings with men who are problem drinkers indicate that fluoxetine differentially alters consummatory behaviors . The reductions in alcohol intake and body weight are of clinical importance BACKGROUND Sleep disturbance may affect smoking cessation efforts . We describe sleep changes across three months among women in a smoking cessation program and tested whether sleep disturbances at baseline and 1 month post-quit attempt predicted smoking status at three months . METHODS Participants ( N=322 ) were women in a r and omized , clinical trial for smoking cessation . Sleep disturbances , as well as , insomnia , drowsiness , and sleep quality were evaluated prior to and during three months of cessation treatment . Repeated measures mixed models evaluated change in sleep over time by smoking outcome status . Logistic regression analyses determined whether sleep disturbances at baseline and 1 month post-quit were associated with smoking status at 3 months . RESULTS Sleep disturbances were reported by more than 25 % of women . Drowsiness , insomnia , and sleep quality changed over time . However , contrary to our hypotheses , none of the sleep variables at either baseline or 1 month post-quit attempt was associated with relapse ( p's>.05 ) . CONCLUSIONS Although mild to severe drowsiness was reported by more women who relapsed than those who remained abstinent , none of the sleep disturbance symptoms predicted smoking relapse . Given high rates of sleep disturbances among women smokers , better prospect i ve evaluations of the relationship of sleep disturbances to smoking cessation treatment outcome are needed BACKGROUND Previous research demonstrated the efficacy of sustained release bupropion ( bupropion SR ) for smoking cessation in whites as well as moderate to heavy ( ≥10 cigarettes per day [ CPD ] ) African American smokers . We evaluated whether bupropion SR was effective for smoking cessation among African American light smokers ( ≤10 CPD ) . METHODS A r and omized , double-blind placebo-controlled trial was conducted from December 27 , 2007 , to May 13 , 2010 . All participants were African American light smokers ( ≤10 CPD ) , aged 18 years or older . Participants were r and omly assigned to receive 300 mg bupropion SR ( 150 mg once daily for 3 days and then 150 mg twice daily ) ( n = 270 participants ) or placebo ( n = 270 participants ) for 7 weeks , and up to six sessions of health education counseling . Serum cotinine was measured at baseline ( week 0 ) . The primary outcome was salivary cotinine-verified 7-day point prevalence smoking abstinence at week 26 ; a cut point of 15 ng/mL differentiated smokers from nonsmokers . Salivary cotinine-verified smoking abstinence at end of medication treatment at week 7 was also examined . Odds ratios ( OR ) for smoking abstinence and 95 % confidence intervals ( CIs ) were calculated using logistic regression models . All statistical tests were two-sided . RESULTS Participants at baseline visit ( week 0 ) smoked an average of 8.0 CPD and had a mean serum cotinine level of 275.8 ng/mL ( SD = 155.8 ng/mL ) ; most used menthol cigarettes ( 83.7 % ) and smoked within 30 minutes of waking ( 72.2 % ) . After imputing those lost to follow-up as smokers , no statistically significant difference in long-term smoking abstinence rates at week 26 was observed between bupropion SR and placebo groups ( 13.3 % vs 10.0 % , OR = 1.39 , 95 % CI = 0.82 to 2.35 , P = .23 ) . Cotinine-verified smoking abstinence rate at end of medication week 7 was higher in the bupropion SR vs placebo group ( 23.7 % vs 9.6 % , OR = 2.92 , 95 % CI = 1.78 to 4.77 , P < .001 ) . CONCLUSIONS Bupropion SR was effective in promoting smoking cessation during the medication phase of treatment but showed no effect on long-term smoking cessation among African American light smokers . More research is needed to identify strategies for sustaining abstinence among African American light smokers While the combination therapy of varenicline and sustained release bupropion ( bupropion SR ) for cigarette smoking cessation can increase smoking abstinence rates , it has also been associated with increases in self-reported depressive symptoms . We conducted an analysis of the Beck Depression Inventory , second edition ( BDI-II ) , data completed by 505 patients from a large r and omized clinical trial , evaluating the efficacy of 12 weeks of combination therapy ( varenicline+bupropion SR ) compared to varenicline alone . At medication treatment week 2 ( 1 week after target quit date [ TQD ] ) , increased depressive symptoms were observed in patients receiving combination therapy ( effect estimate=0.61 , 95 % CI [ 0.03 , 1.19 ] , P=.039 ) and those with a history of depression ( effect estimate=0.82 , 95 % CI [ 0.07 , 1.57 ] , P=.033 ) . For treatment weeks 2 to 4 , smokers with a history of depression on combination therapy had a greater decline in depressive symptoms compared to those on varenicline alone ( effect estimate=-1.99 , 95 % CI [ -3.99 , 0.00 ] , P=.050 ) . After treatment week 4 , no significant effects of treatment or depression history on BDI-II scores were observed . A history of depression did not moderate the efficacy of combination therapy for smoking abstinence . Our study suggests that for combination therapy with varenicline and bupropion SR , an increase in depressive symptoms over the first 2 weeks may be observed ; however , the effects on depressive symptoms do not last beyond 4 weeks . We conclude that among smokers without active moderate or severe depression , the decision to use this combination treatment approach should not be based upon a self-reported history of depression The A1 allele of the dopamine D2 receptor gene ( DRD2 ) is associated with a reduced number of dopamine binding sites in the brain and with the increased likelihood of substance abuse and addictive behavior . In a study of smokers enrolled in an open-label , r and omized effectiveness trial , we investigated whether variants in the DRD2 receptor gene are associated with smoking cessation outcomes following treatment with a combination of bupropion SR and behavioral counseling . Adherence to treatment and point-prevalent smoking status were assessed at 3 and 12 months , respectively , following a target quit date . Compared to women who carry both A2 alleles , women with at least one A1 allele were more likely to report having stopped taking bupropion due to medication side effects ( odds ratio (OR)=1.91 , 95 % confidence interval (CI)=1.01–3.60 ; P<0.04 ) and at 12 months were somewhat more likely to report smoking ( OR=0.76 , 95 % CI=0.56–1.03 ; P<0.076 ) . Significant associations or trends were not observed in men . In women , individual variability in responsiveness to bupropion-based treatment may be partially due to differences in genetic variants influencing dopamine receptor function INTRODUCTION To determine the cost-effectiveness of a high-intensity smoking cessation program ( SmokeStop Therapy ; SST ) versus a medium-intensity treatment ( Minimal Intervention Strategy for Lung patients [ LMIS ] ) for chronic obstructive pulmonary disease out patients . METHODS The cost-effectiveness analysis was based on a r and omized controlled trial investigating the effectiveness of the SST compared with the LMIS with 12-month follow-up . The primary outcome measure was the cotinine-vali date d continuous abstinence rate based on intention to treat . A health care perspective was adopted , with outcomes assessed in terms of ( incremental ) additional quitters gained , exacerbations prevented , and hospital days prevented . Health care re source use , associated with smoking cessation , was collected at baseline and 12 months after the start of the interventions . Monte Carlo simulations were performed to evaluate the robustness of the results . RESULTS The average patient receiving SST generated € 581 in health care costs , including the costs of the smoking cessation program , versus € 595 in the LMIS . The SST is also associated with a lower average number of exacerbations ( 0.38 vs. 0.60 ) and hospital days ( 0.39 vs. 1 ) per patient and a higher number of quitters ( 20 vs. 9 ) at lower total costs . This leads to a dominance of the SST compared with the LMIS . CONCLUSIONS The high-intensive SST is more cost-effective than the medium-intensive LMIS after 1 year . This is associated with cost savings per additional quitter , prevented exacerbations , and hospital days at lower or equal costs Rationale Tobacco withdrawal is a key factor in smoking relapse , but important questions about the withdrawal phenomenon remain . Objectives This research was intended to provide information about two core components of withdrawal ( negative affect and craving ) : ( 1 ) how various withdrawal symptom profile dimensions ( e.g. , mean level , volatility , extreme values ) differ between negative affect and craving ; and ( 2 ) how these dimensions relate to cessation outcome . Methods Adult smokers ( N = 1,504 ) in a double-blind r and omized placebo-controlled smoking cessation trial provided real-time withdrawal symptom data four times per day for 4 weeks ( 2 weeks pre-quit and 2 weeks post-quit ) via palmtop computers . Cessation outcome was biochemically confirmed 8-week point-prevalence abstinence . Results Examination of craving and negative affect dimensions following a cessation attempt revealed that craving symptoms differed from negative affect symptoms , with higher means , greater variability , and a greater incidence of extreme peaks . Regression analyses revealed that abstinence was associated with lower mean levels of both craving and negative affect and fewer incidences of extreme craving peaks . In a multivariate model , the increase in mean craving and negative affect scores each uniquely predicted relapse . Conclusions Real-time reports revealed different patterns of abstinence-related negative affect and craving and that dimensions of both predict cessation outcome , suggesting that negative affect and craving dimensions each has motivational significance . This underscores the complexity of withdrawal as a determinant of relapse and the need to measure its distinct components and dimensions Efficacy of bupropion SR and individual counseling as smoking cessation treatments was assessed in a r and omized , placebo-controlled clinical trial among adult daily smokers . Bupropion SR treatment and counseling were fully crossed in this factorial design so that the efficacy of each treatment and the combination could be estimated , relative to a placebo medication and assessment control condition . Intent-to-treat analyses indicated that bupropion SR increased abstinence rates at the end of treatment , relative to the placebo medication conditions , for both biochemically confirmed 7-day point-prevalence abstinence ( OR = 1.97 , 95 % CI 1.04 - 3.72 ) and self-reported prolonged abstinence ( OR = 2.90 , 95 % CI 1.66 - 5.06 ) . Bupropion SR treatment also improved latency to lapse and relapse and improved the latency between lapse and relapse in survival analyses . Medication effects were more modest for both 12-month point-prevalence abstinence ( OR = 1.47 , 95 % CI 0.74 - 2.92 ) and prolonged abstinence ( OR = 1.34 , 95 % CI 0.66 - 2.72 ) . Counseling was not associated with increases in the likelihood of abstinence at any time point ( odds ratios ranged from 0.80 to 1.16 across abstinence outcomes in the full intent-to-treat sample ) . Counseling and medication did not significantly interact at any time point , and adding counseling did not improve end-of-treatment point-prevalence abstinence ( OR = 1.17 , 95 % CI 0.68 - 2.03 ) or prolonged abstinence ( OR = 1.26 , 95 % CI 0.75 - 2.12 ) substantially when offered in conjunction with active medication This study compares the effectiveness and tolerability of bupropion versus bupropion plus nicotine patch for smoking cessation in a routine clinical setting . Patients at the Sepulveda Veterans Health Administration Smoking Cessation Clinic completed a baseline survey and received counseling over 2 months , along with bupropion or bupropion plus nicotine patch . Of the 227 patients r and omized to treatment , 112 ( 49 % ) received bupropion only and 115 ( 51 % ) received the combination therapy . At least one side effect was noted in 55 % of bupropion patients and 70 % of combination therapy patients ; treatment regimens were changed in 7 % and 14 % , respectively . Abstinence rates at 2 months were 26 % for the bupropion group and 37 % for the combination therapy group ( p = 0.1 ) , and at 6 months were 42 % versus 35 % , respectively ( p = 0.4 ) . Although 6-month abstinence rates were derived from patient self-report and should be interpreted with caution , these results suggest that most patients referred to the clinic are able to take these medications . There was no difference in the rate of switching treatments , or in long-term abstinence rates Many persons who attempt to quit smoking have made previous unsuccessful attempts to quit with pharmacologic aids . An underst and ing of the impact of these previous attempts to quit is vital for selecting medications that may be more successful in a future attempt to quit . In particular , the effect of repeated use of bupropion SR ( Zyban ; INN , amfebutamone ) on abstinence rates has not been studied previously OBJECTIVE The authors evaluated an adaptive smoking cessation treatment strategy in which nicotine patch treatment was initiated before a quit date , and then , depending on initial therapeutic response , either the nicotine patch was continued or alternative pharmacotherapies were provided . METHOD The study was a double-blind , parallel-arm adaptive treatment trial . A total of 606 cigarette smokers started open-label nicotine patch treatment 2 weeks before the quit date . Those whose ad lib smoking did not decrease by > 50 % after 1 week were r and omly assigned to one of three double-blind treatments : nicotine patch alone ( control condition ) ; " rescue " treatment with bupropion augmentation of the patch ; or rescue treatment with varenicline alone . Participants whose precessation smoking decreased > 50 % but who lapsed after the quit date were also r and omly assigned to the two rescue treatments or to nicotine patch alone . Logistic regression analyses compared each rescue treatment against the control condition in terms of abstinence at the end of treatment ( weeks 8 - 11 ) and at 6 months . RESULTS Smokers who did not respond adequately to precessation nicotine patch benefited from bupropion augmentation ; abstinence rates at end of treatment were 16 % with nicotine patch alone and 28 % with bupropion augmentation ( odds ratio=2.04 , 95 % CI=1.03 - 4.01 ) . Switching to varenicline produced less robust effects , but point abstinence at 6 months was 6.6 % with the patch alone and 16.5 % with a switch to varenicline ( odds ratio=2.80 , 95 % CI=1.11 - 7.06 ) . Postquit adaptive changes in treatment had no significant effects on any abstinence outcome . CONCLUSIONS It is possible to rescue a significant portion of smokers who would have failed to achieve abstinence if left on nicotine patch alone by identifying these smokers before their quit date and implementing adaptive changes in treatment INTRODUCTION Legal restrictions have contributed to the decline in smoking prevalence in several European countries . We investigated the impact of the Italian 2005 indoor smoking ban on the efficacy of counseling alone or in combination with bupropion for smoking cessation . METHODS Before and after the introduction of the ban ( 2001 - 2006 ) , 550 smokers were enrolled in the smoking cessation program in Rome and were asked to choose between a 6-week group counseling therapy ( GCT ) given alone or in combination with 7 weeks of daily bupropion . Follow-up was completed 12 , 26 , and 52 weeks after the quit day . Due to the observational nature of the study , we used propensity scores to match 138 and 290 subjects ( pre-/postban ) in the bupropion- and GCT-only groups , respectively . RESULTS Covariate balance in the two matched sample s was adequate for all variables except " coffee consumption " in the GCT-only group . The regression adjusted odds ratios indicated that the introduction of the ban result ed in 52 % reduced odds of continued smoking at 12 months among the GCT + bupropion group and 41 % reduced odds in the GCT-only group . We observed that the ban was associated with both increased 12-month abstinence rates and motivation to quit . In a mediation analysis , we determined that the total effect of the smoking ban on the abstinence rate was reduced after controlling for motivation , which confirmed that motivation was a partial mediator . DISCUSSION The introduction of an indoor smoking ban improved the efficacy of smoking cessation treatments by possibly providing a setting that increased the level of motivation to stop smoking AIMS To investigate the safety and efficacy of bupropion sustained release ( bupropion SR ) in promoting abstinence from smoking in subjects with cardiovascular disease ( CVD ) . METHODS Six hundred twenty-nine subjects with CVD who smoked > /=10 cigarettes/day were r and omised in a double-blind , multicentre study to receive bupropion SR ( 150 mg twice daily ) or placebo for 7 weeks , with a follow-up of 52 weeks . Primary efficacy endpoint : continuous abstinence from smoking from weeks 4 to 7 . Secondary endpoints : continuous abstinence ( weeks 4 - 12 , 4 - 26 and 4 - 52 ) and weekly point prevalence abstinence . All participants received brief motivational support . Safety was evaluated throughout the study . RESULTS Continuous smoking abstinence rates from weeks 4 to 7 were significantly higher in subjects receiving bupropion SR compared with placebo ( 43 vs. 19 % , odds ratio [OR]=3.27 , 95 % confidence interval [ CI ] 2.24 - 4.84 ; P<0.001 ) . Continuous abstinence rates from weeks 4 to 26 and 4 to 52 continued to be more than double for bupropion SR compared with placebo ( 27 vs. 11 % ; 22 vs. 9 % , P<0.001 ) . Weekly point prevalence abstinence was significantly higher for participants who received bupropion SR compared with placebo at weeks 3 , 7 , 26 and 52 ( P<0.001 ) . In both groups , there were no clinical ly significant changes in blood pressure and heart rate throughout the treatment phase . Overall , 6 % of the participants ( n=36 ) discontinued study medication due to an adverse event ( bupropion SR , n=17 ; placebo , n=19 ) . CONCLUSIONS After 7 weeks of bupropion SR treatment , more than twice as many smokers with CVD had quit smoking at 1 year compared with placebo . The safety profile of bupropion SR was similar to that previously observed in general smoking population AIMS Nicotine replacement therapy ( NRT ) is an established aid in stopping smoking , while the role of antidepressants remains uncertain . Antidepressants added to NRT might improve abstinence rates . Our aim was to determine the efficacy of nicotine inhaler and fluoxetine vs. nicotine inhaler and placebo in attempts to quit smoking . DESIGN A r and omized , double-blind , placebo-controlled trial . SETTING A smoker 's cessation clinic . PARTICIPANTS One hundred volunteers smoking 10 cigarettes/day or more . INTERVENTIONS Subjects were instructed to start taking a daily dose of 10 mg of fluoxetine or placebo 16 days before stopping smoking , then 20 mg 10 days before quitting , continuing for up to at least 3 months . Subjects were instructed to use 6 - 12 units per day of nicotine inhalers after stopping smoking for up to 6 months . MEASUREMENTS Continuous abstinence rates recorded at various time points up to 12 months from the quit date . FINDINGS The sustained abstinence rate for the inhaler-fluoxetine group was 54 % , 40 % , 29 % and 21 % after 1.5 , 3 , 6 and 12 months , respectively , compared to 48 % , 40 % , 32 % and 23 % for the inhaler-placebo group . The differences were not significant at any time point . Abstinence up to 3 months was more likely in older smokers , those with a lower Beck Depression Inventory Score ( BDI ) , lower Fagerström Test of Nicotine Dependence ( FTND ) score and no history of alcoholism . Fluoxetine appeared to increase abstinence rates among high BDI smokers compared to high BDI smokers assigned placebo . Serum levels of nicotine during treatment in the inhaler-fluoxetine group were lower than in the inhaler-placebo group so that fluoxetine may have reduced inhaler use through a common site of action . CONCLUSIONS We found no evidence that fluoxetine treatment when used as an adjunct to NRT in unselected smokers is effective , but there may be an advantage to using it in depressed smokers Background : Smoking now represents one of the biggest modifiable risk factors for disease and mortality in people living with HIV ( PLHIV ) . To produce significant changes in smoking rates among this population , treatments will need to be both acceptable to the larger segment of PLHIV smokers and feasible to implement in busy HIV clinics . The purpose of this study was to evaluate the feasibility and effects of a novel proactive algorithm-based intervention in an HIV/AIDS clinic . Methods : PLHIV smokers ( N = 100 ) were proactively identified through their electronic medical records and were subsequently r and omized at baseline to receive a 12-week pharmacotherapy-based algorithm treatment or treatment as usual . Participants were tracked in-person for 12 weeks . Participants provided information on smoking behaviors and associated constructs of cessation at each follow-up session . Results : The findings revealed that many smokers reported using prescribed medications when provided with a supply of cessation medication as determined by an algorithm . Compared with smokers receiving treatment as usual , PLHIV smokers prescribed these medications reported more quit attempts and greater reduction in smoking . Proxy measures of cessation readiness ( eg , motivation , self-efficacy ) also favored participants receiving algorithm treatment . Conclusions : This algorithm-derived treatment produced positive changes across a number of important clinical markers associated with smoking cessation . Given these promising findings coupled with the brief nature of this treatment , the overall pattern of results suggests strong potential for dissemination into clinical setting s and significant promise for further advancing clinical health outcomes in this population This study evaluated the ability of polymorphisms in five c and i date genes to predict weight gain among patients taking bupropion or placebo in a smoking cessation trial . Five hundred fifty-three smokers were enrolled into a r and omized double-blind , placebo-controlled trial and followed for 12 months . Five c and i date genes [ DRD2 Taq1 ( rs1800497 ) , DRD2 - 141 ( rs1799732 ) , C957 T ( rs6277 ) , COMT ( rs4818 ) , and SLC6A3 ] were genotyped . Weights at baseline , at end of treatment , and after 6 and 12 months of follow-up were self-reported . Smoking abstinence at each endpoint was self-reported and confirmed biochemically . A self-reported average weight gain after 12 months of 1.1 + /- 6.0 kg ( mean + /- st and ard deviation ) in the bupropion group and 1.8 + /- 4.8 kg in the placebo group was noted . For subjects with biochemically confirmed abstinence from smoking , the HL genotype ( alleles coding Val at codon 108 are denoted as H , and those coding Met are denoted as L ) at the COMT locus and A1A1 genotype at the DRD2 Taq1 locus were associated with less weight gain at the end of treatment . The TC genotype at the C957 T locus was associated with increased weight gain at 6 months of follow-up . However , no polymorphisms or their interactions with bupropion consistently and significantly predicted baseline BMI or weight change during treatment for all study subjects . Overall , our results do not support a major role for these five c and i date genes in weight gain after smoking cessation BACKGROUND The observations that smokers with chronic obstructive pulmonary disease ( COPD ) are at increased risk of depression and that nicotine may have antidepressant effects and regulate mood provide a rationale for the use of antidepressant drugs for smoking cessation in patients with COPD . No clinical trial has studied the efficacy of bupropion hydrochloride and nortriptyline hydrochloride for smoking cessation in this patient population , to our knowledge . METHODS In a placebo-controlled double-dummy r and omized trial , 255 adults at risk for COPD or with COPD were prescribed sustained-release bupropion ( bupropion SR ) ( 150 mg twice daily ) or nortriptyline ( 75 mg once daily ) for 12 weeks . All patients received smoking cessation counseling . The main outcome measure was prolonged abstinence from smoking from week 4 to week 26 after the target quit date . RESULTS The use of bupropion SR and nortriptyline result ed in higher prolonged abstinence rates compared with placebo , although only the difference between bupropion SR and placebo was statistically significant ( differences with placebo , 13.1 % [ 95 % confidence interval , 1.2%-25.1 % ] for bupropion SR and 10.2 % [ 95 % confidence interval , -1.7 % to 22.2 % ] for nortriptyline ) . In patients with COPD , bupropion SR and nortriptyline seem efficacious in achieving prolonged abstinence ( differences with placebo , 18.9 % [ 95 % confidence interval , 3.6%-34.2 % ] for bupropion SR and 12.9 % [ 95 % confidence interval , -0.8 % to 26.4 % ] for nortriptyline ) . In participants at risk for COPD , no statistically significant differences with placebo in prolonged abstinence rates were found . CONCLUSIONS Bupropion SR treatment is an efficacious aid to smoking cessation in patients with COPD . Nortriptyline treatment seems to be a useful alternative BACKGROUND Previous published studies assessed the efficacy of bupropion in smoking cessation only in North American population s of smokers . Results of therapeutic drug trials are not always directly applicable in other population s. AIMS To confirm the efficacy of bupropion in smoking cessation in European smokers . DESIGN A multi-centre , r and omized , double-blind placebo-controlled trial . SETTING Seventy-four smoking cessation out-patient clinics in France . PARTICIPANTS The study included 509 smokers motivated to quit smoking . Intervention Subjects were r and omized to either slow-release bupropion 150 mg b.i.d . ( B ) or to placebo ( Pl ) in a 2 : 1 ratio , treated for 7 weeks , and followed-up for 26 weeks . MEASUREMENTS MAIN OUTCOME MEASURE 6 months ' point prevalence abstinence , determined by self-report and expired air carbon monoxide measurement . SECONDARY OUTCOME MEASURES weeks 4 - 7 and weeks 4 - 26 continuous abstinence rates , craving , withdrawal symptoms , weight and cigarette consumption in smokers unable to quit . Adverse events were recorded systematic ally . FINDINGS Six months ' point prevalence abstinence rates were 31 % and 16%[odds ratio = 2.3 , confidence interval ( CI ) 95 % : 1.4 - 3.7 ] in the B and Pl groups , respectively . Continuous abstinence rates were 41 % ( B ) and 21 % ( P ) with OR = 2.5 ( CI 95 % : 1.6 - 3.9 ) for weeks 4 - 7 , and 25 % ( B ) and 13 % ( P ) with OR = 2.2 ( CI 95 % : 1.3 - 3.6 ) for weeks 4 - 26 , respectively . Craving decreased significantly more with B than with Pl during treatment period , but there was no difference for total withdrawal symptoms score . Abstinent subjects gained significantly less weight at week 7 with B than with Pl . Low level of nicotine dependence , high motivation , absence of smoking-related disease , long duration of previous quit attempts , male gender , low level of current alcohol problems and living as a couple were predictive of successful cessation . With the exception of marital status , no interaction was observed between any of these predictive factors and the efficacy of bupropion . More of those who continued smoking in the B group than the P group reduced their consumption by at least 50 % . CONCLUSIONS Sustained-release bupropion is efficacious as an aid to smoking cessation in European smokers . No outcome predictors were identified that might indicate that certain subgroups of smokers would benefit more than others from treatment with bupropion Background Smoking cessation rates with current therapy are suboptimal . Tricyclic antidepressants improve cessation rates . We hypothesized that addition of nortriptyline hydrochloride to transdermal nicotine would enhance cessation rates . Methods We conducted a r and omized , double-blind , placebo-controlled trial at a Department of Veterans Affairs medical center . Subjects were aged 18 to 65 years , smoked 10 or more cigarettes per day , and did not have current major depression . Nortriptyline hydrochloride or matched placebo was started at 25 mg 14 days before quit day , titrated to 75 mg/d as tolerated , and continued for 12 weeks after quit day . Transdermal nicotine ( 21 mg/d ) was started on quit day and continued for 8 weeks . The behavioral intervention consisted of 12 brief , individual visits . Withdrawal symptoms were measured by means of a daily diary , and smoking cessation was defined as self-reported abstinence , expired carbon monoxide level of 9 ppm or less , and a 6-month urine cotinine level less than 50 ng/mL ( 284 nmol/L ) . Results A total of 158 patients were r and omized ( 79 to nortriptyline and 79 to placebo ) . There was no significant reduction in withdrawal symptoms . The cessation rates at 6 months were 23 % ( 18/79 ) and 10 % ( 8/79 ) , respectively ( absolute difference , 13 % ; 95 % confidence interval , 1.3%-24.5 % ; P = .052 ) . Nortriptyline caused frequent side effects , including dry mouth ( 38 % ) and sedation ( 20 % ) . Conclusions Nortriptyline combined with transdermal nicotine result ed in an increased cessation rate with little effect on withdrawal symptoms . This combination may represent an option for smokers in whom st and ard therapy has failed Prospect theory suggests that because smoking cessation is a prevention behavior with a fairly certain outcome , gain-framed messages will be more persuasive than loss-framed messages when attempting to encourage smoking cessation . To test this hypothesis , the authors r and omly assigned participants ( N=258 ) in a clinical trial to either a gain- or loss-framed condition , in which they received factually equivalent video and printed messages encouraging smoking cessation that emphasized either the benefits of quitting ( gains ) or the costs of continuing to smoke ( losses ) , respectively . All participants received open label sustained-release bupropion ( 300 mg/day ) for 7 weeks . In the intent-to-treat analysis , the difference between the experimental groups by either point prevalence or continuous abstinence was not statistically significant . Among 170 treatment completers , however , a significantly higher proportion of participants were continuously abstinent in the gain-framed condition as compared with the loss-framed condition . These data suggest that gain-framed messages may be more persuasive than loss-framed messages in promoting early success in smoking cessation for participants who are engaged in treatment Introduction Rates of smoking in the US population have decreased overall , but rates in some groups , including alcoholic smokers , remain high . Many newly sober alcoholics are concerned about their smoking and some attempt to quit . However , quit rates in this population are low . Prior studies suggest risk for relapse in this population may be genetically influenced and that genetic factors may moderate response to treatment . Methods In this exploratory study , we had two specific aims : ( 1 ) to investigate associations between genetic risk and outcome ; ( 2 ) to investigate whether genetic risk moderates the efficacy of a medication intervention . Data are from a sub sample of 90 participants from a clinical trial of smoking cessation treatment for smokers with between 2 and 12 months of alcohol abstinence . Subjects were r and omly assigned to bupropion or placebo . All subjects received counseling and nicotine patches . To examine the possibility that bupropion may have been efficacious in participants with a specific genetic profile ( ie , a pharmacogenetic approach ) , an aggregate genetic risk score was created by combining risk genotypes previously identified in bupropion treatment studies . Results Although medication efficacy was not moderated by the aggregate genetic risk score , there was an interaction between nicotine dependence and genetic risk in predicting smoking abstinence rates at the end of treatment ( 10 weeks ) . Conclusions Results suggest an aggregate genetic risk score approach may have utility in treatment trials of alcoholics who smoke . Additionally , these findings suggest a strategy for underst and ing and interpreting conflicting results for single genetic markers examined as moderators of smoking cessation treatment INTRODUCTION Despite tremendous potential public health impact , little work has focused on development of evidence -based smoking cessation treatments for adolescents , including pharmacotherapies . No prior studies have explored the feasibility and safety of varenicline and bupropion XL , 2 potentially promising pharmacotherapies , as smoking cessation treatments in adolescents . METHODS Treatment-seeking older adolescent smokers ( ages 15 - 20 ) were r and omized ( double-blind ) to varenicline ( n = 15 ) or bupropion XL ( n = 14 ) , with 1-week titration and active treatment for 7 weeks . Structured safety , tolerability , and efficacy assessment s ( cotinine-confirmed 7-day point prevalence abstinence ) were conducted weekly . RESULTS There were no serious adverse events . Two participants discontinued bupropion XL due to adverse effects , and none discontinued varenicline . Over the course of treatment , participants receiving varenicline reduced from 14.1 ± 6.3 ( mean ± SD ) to 0.9 ± 2.1 cigarettes/day ( CPD , 4 achieved abstinence ) , while those receiving bupropion XL reduced from 15.8 ± 4.4 to 3.1 ± 4.0 CPD ( 2 achieved abstinence ) . CONCLUSIONS These preliminary results support the feasibility and safety of conducting adequately powered , placebo-controlled efficacy studies of varenicline and bupropion XL for adolescent smoking cessation IMPORTANCE Combining pharmacotherapies for tobacco-dependence treatment may increase smoking abstinence . OBJECTIVE To determine efficacy and safety of varenicline and bupropion sustained-release ( SR ; combination therapy ) compared with varenicline ( monotherapy ) in cigarette smokers . DESIGN , SETTING , AND PARTICIPANTS R and omized , blinded , placebo-controlled multicenter clinical trial with a 12-week treatment period and follow-up through week 52 conducted between October 2009 and April 2013 at 3 midwestern clinical research sites . Five hundred six adult ( ≥18 years ) cigarette smokers were r and omly assigned and 315 ( 62 % ) completed the study . INTERVENTIONS Twelve weeks of varenicline and bupropion SR or varenicline and placebo . MAIN OUTCOMES AND MEASURES Primary outcome was abstinence rates at week 12 , defined as prolonged ( no smoking from 2 weeks after the target quit date ) abstinence and 7-day point-prevalence ( no smoking past 7 days ) abstinence . Secondary outcomes were prolonged and point-prevalence smoking abstinence rates at weeks 26 and 52 . Outcomes were biochemically confirmed . RESULTS At 12 weeks , 53.0 % of the combination therapy group achieved prolonged smoking abstinence and 56.2 % achieved 7-day point-prevalence smoking abstinence compared with 43.2 % and 48.6 % in varenicline monotherapy ( odds ratio [ OR ] , 1.49 ; 95 % CI , 1.05 - 2.12 ; P = .03 and OR , 1.36 ; 95 % CI , 0.95 - 1.93 ; P = .09 , respectively ) . At 26 weeks , 36.6 % of the combination therapy group achieved prolonged and 38.2 % achieved 7-day point-prevalence smoking abstinence compared with 27.6 % and 31.9 % in varenicline monotherapy ( OR , 1.52 ; 95 % CI , 1.04 - 2.22 ; P = .03 and OR , 1.32 ; 95 % CI , 0.91 - 1.91 ; P = .14 , respectively ) . At 52 weeks , 30.9 % of the combination therapy group achieved prolonged and 36.6 % achieved 7-day point-prevalence smoking abstinence compared with 24.5 % and 29.2 % in varenicline monotherapy ( OR , 1.39 ; 95 % CI , 0.93 - 2.07 ; P = .11 and OR , 1.40 ; 95 % CI , 0.96 - 2.05 ; P = .08 , respectively ) . Participants receiving combination therapy reported more anxiety ( 7.2 % vs 3.1 % ; P = .04 ) and depressive symptoms ( 3.6 % vs 0.8 % ; P = .03 ) . CONCLUSIONS AND RELEVANCE Among cigarette smokers , combined use of varenicline and bupropion , compared with varenicline alone , increased prolonged abstinence but not 7-day point prevalence at 12 and 26 weeks . Neither outcome was significantly different at 52 weeks . Further research is required to determine the role of combination therapy in smoking cessation . TRIAL REGISTRATION clinical trials.gov Identifier : http:// clinical trials.gov/show/NCT00935818 OBJECTIVES To determine the relationship between white blood cell ( WBC ) Indices and several baseline variables In a large cohort of healthy smokers and to assess whether these changed after biochemically confirmed smoking cessation . SUBJECTS AND METHODS The study consisted of 784 healthy smokers enrolled in a trial of sustained-release bupropion , 300 mg/d , for relapse prevention after smoking cessation from 1995 to 1998 . Both WBC counts and absolute neutrophil counts ( ANCs ) were measured at baseline , week 7 , and week 52 . Smoking status was assessed at weeks 7 and 52 by self-report and biochemically confirmed with expired air carbon monoxide levels . Multivariate analyses compared changes in WBC count and ANC between smokers who did and did not stop smoking , adjusting for treatment group , age , sex , and body mass index . RESULTS Of 784 smokers enrolled , 461 had biochemically confirmed tobacco abstinence after 7 weeks of bupropion ; 429 were r and omly assigned to receive continued bupropion therapy or placebo until week 52 . Between baseline and week 7 , there was a significantly larger decrease in WBC count in continuously abstinent subjects compared with continuing smokers ( adjusted P = .03 ) . At 52 weeks , continuously abstinent subjects , compared with continuing smokers , had a greater decline from baseline in WBC count ( 1.2 + /- 1.9 x 10(9)/L vs 0.1 + /- 1.9 x 10(9)/L ; P < .001 ) and ANC ( 1.0 + /- 1.6 x 10(9)/L vs 0.2 + /- 1.5 x 10(9)/L ; P < .001 ) . CONCLUSION Biochemically confirmed tobacco abstinence leads to a rapid and sustained decrease in WBC and ANC , possibly reflecting a decrease In an underlying state of tobacco-induced inflammation OBJECTIVE To assess the safety and efficacy of sustained-release bupropion hydrochloride for adolescent smoking cessation . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled , dose-ranging trial . SETTING Metropolitan areas of Tucson and Phoenix , Arizona . PARTICIPANTS Adolescents ( N = 312 ) recruited through media and various community venues from March 1 , 1999 , through December 31 , 2002 , who were aged 14 to 17 years , smoked 6 or more cigarettes per day , had an exhaled carbon monoxide level of 10 ppm or greater , had at least 2 previous quit attempts , and had no other current major psychiatric diagnosis . INTERVENTION Sustained-release bupropion hydrochloride , 150 mg/d ( n = 105 ) or 300 mg/d ( n = 104 ) , or placebo ( n = 103 ) for 6 weeks , plus weekly brief individual counseling . Subjects were followed up at 12 weeks ( by telephone call ) and 26 weeks . MAIN OUTCOME MEASURE Confirmed 7-day point prevalence abstinence at 6 weeks and 30-day prolonged abstinence ( carbon monoxide level < 10 ppm at each visit ; urinary cotinine level < or = 50 microg/L at weeks 2 and 6 ) . RESULTS Cotinine-confirmed 7-day point prevalence abstinence rates at 6 weeks were as follows : placebo , 5.6 % ; 150 mg , 10.7 % ; and 300 mg , 14.5 % ( P = .03 , 300 mg vs placebo ) . At 26 weeks , confirmed point prevalence abstinence rates were as follows : placebo , 10.3 % ; 150 mg , 3.1 % ; and 300 mg , 13.9 % ( P = .049 ) . During treatment , confirmed point prevalence rates were significantly higher for 300 mg than placebo at every week except week 4 . CONCLUSIONS Sustained-release bupropion hydrochloride , 300 mg/d , plus brief counseling demonstrated short-term efficacy for adolescent smoking cessation . Abstinence rates were lower than those reported for adults , with rapid relapse after medication discontinuation . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00344695 Past history of major depression is more common in smokers than in non-smokers . We have shown in a previous study that lifetime prevalence of major depression is higher in dependent smokers and they have lower monoamine oxidase-A and -B activities than non-smokers . Because several studies have found an association between MAO-B activity and depression we analysed data of these smokers to assess whether past history of major depression is associated with reduced monoamine oxidase activities ( A and B ) or not . Further , we tried to characterize smokers with past history of major depression and its effect on withdrawal symptoms . The data of 88 dependent smokers ( Fagerström Tolerance Question naire score > or = 6 and smoking > or = 20 cigarettes/day ) who participated in a smoking cessation study were analysed . Smokers with past history of major depression but without current illness did not differ in demographic and smoking characteristics from smokers without past history of major depression . Smokers with past history of major depression were mainly women and had lower body mass index . Adjusted for gender and body mass index dependent smokers with or without past history of depression had similar MAO-A and MAO-B activities but smokers with past history of major depression had significantly lower resting plasma norepinephrine levels . Smokers with past history of depression had not significantly higher ratings for depression ( Montgomery-Asberg Depression Rating Scales ) and anxiety ( Hamilton Anxiety Scales ) and smoking cessation did not exacerbate these ratings ( assessed up to 3 months ) and none had depressive episode during the postcessation period up to one year . Past history of depression was associated with higher scores on ' expressed sadness ' and ' depressive mood ' . Abstinent smokers with past history of depression had significantly higher ratings in one of the seven ratings of a 6 months period for craving ( day 28 ) , anxiety ( day 7 ) and total withdrawal symptom score ( day 7 ) when compared to those who had no past history of major depression . It is concluded that ( i ) past history of major depression is more frequent in female smokers ; ( ii ) smokers with past history of depression may have more intense withdrawal symptoms ( craving and anxiety ) at some time after cessation : and ( iii ) past history of depression does not affect monoamine oxidase activities , therefore , reduced monoamine oxidase activities found in previous studies are possibly characteristic features of smoking The aim of this study was to identify predictors of successful relapse prevention in smokers receiving long-term sustained-release bupropion . Smokers ( N= 784 ) who were interested in stopping smoking were enrolled in a 7-week , open-label bupropion phase . Abstinent subjects at the end of treatment and eligible to proceed ( N= 429 ) were r and omized to active bupropion or placebo through Week 52 and then followed for an additional year . The best overall predictor of less relapse to smoking was assignment to active bupropion . In aggregate , the results indicate that bupropion can be prescribed to diverse population s of smokers with expected comparable results . There was a medication effect that was independent of any predictor except older age and those who gained no or minimal weight during the open-label phase . Predictors of successful relapse prevention included lower baseline smoking rates , a Fagerström Tolerance Question naire score of < 6 , and initiation of smoking at an older age . These data should encourage others to perform similar pharmacologic relapse prevention studies with this or other pharmacotherapies IMPORTANCE Given the actions of varenicline tartrate and bupropion hydrochloride sustained-release ( SR ) on neurobiological targets related to affect and reward , it is thought that the modulation of nicotine withdrawal symptoms may contribute to their effectiveness . OBJECTIVE To assess the relative efficacy of varenicline and bupropion SR plus intensive counseling on smoking cessation and emotional functioning . DESIGN AND SETTING Placebo-controlled r and omized clinical trial at a university medical center . PARTICIPANTS In total , 294 community volunteers who wanted to quit smoking . INTERVENTIONS Twelve weeks of varenicline , bupropion SR , or placebo plus intensive smoking cessation counseling ( 10 sessions , for a total of approximately 240 minutes of counseling ) . MAIN OUTCOME MEASURES Prolonged abstinence from smoking and weekly measures of depression , negative affect , and other symptoms of nicotine withdrawal . RESULTS Significant differences were found in abstinence at the end of treatment and through the 3-month postquit follow-up visit , favoring both active medications compared with placebo . At the 6-month postquit follow-up visit , only the varenicline vs placebo comparison remained significant . Varenicline use was also associated with a generalized suppression of depression and reduced smoking reward compared with the other treatments , while both active medications improved concentration , reduced craving , and decreased negative affect and sadness compared with placebo , while having little effect ( increase or decrease ) on anxiety and anger . No differences were noted in self-reported rates of neuropsychiatric adverse events . CONCLUSIONS AND RELEVANCE In a community sample , varenicline exerts a robust and favorable effect on smoking cessation relative to placebo and may have a favorable ( suppressive ) effect on symptoms of depression and other affective measures , with no clear unfavorable effect on neuropsychiatric adverse events . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00507728 In a double-blind study , 19 adults received bedtime doses of either 150 mg of doxepin hydrochloride ( N = 9 ) or placebo ( N = 10 ) . After 3 weeks the subjects were instructed to stop smoking and continue taking medication for 4 additional weeks . Cessation was reported by all nine doxepin subjects 1 week after cessation and by seven doxepin subjects 9 weeks after cessation . One placebo subject reported cessation . Cotinine assays generally confirmed cessation but were subject to interpretation . Doxepin assays suggested that the precessation level was associated with cessation . Further studies with larger sample s and extended follow-up are needed to determine the reliability of these results The effect of fluoxetine hydrochloride , a 5-HT uptake inhibitor ( 60 mg/day PO ) , in preventing weight gain associated with nicotine reduction was investigated in participants in a double-blind , placebo-controlled smoking-cessation trial . A lunch of cheese pizza and chocolate bars was offered , and caloric intake was monitored . The analysis focused on subjects ( placebo : n = 11 ; fluoxetine : n = 10 ) who succeeded in reaching cotinine levels of less than 50 % of their starting cotinine levels ( signifying a stringent reduction in nicotine intake ) and who participated in pre- and post-nicotine reduction lunch sessions 70 days apart . Subjects on placebo gained significantly more weight ( mean + /- SEM = + 3.3 + /- 0.7 kg ) than subjects on fluoxetine ( -0.6 + /- 1.2 kg ) . In fluoxetine-treated subjects , weight gain/loss was strongly correlated with initial body mass index , with higher BMI being associated with greater decreases in weight . A trend towards decreased caloric intake in the fluoxetine group was observed ; the change in total calories at lunch was significantly correlated with weight change , an association accounted for principally by change in pizza intake . We conclude that fluoxetine treatment effectively prevents the weight gain that accompanies nicotine reduction and that this phenomenon is mediated , at least in part , by diminished caloric intake BACKGROUND Smokers hospitalized with acute coronary syndrome ( ACS ) are at high risk for subsequent ischemic events . Nevertheless , over two-thirds of patients continue to smoke after an acute myocardial infa rct ion . Bupropion hydrochloride has proven efficacy as a smoking cessation aid , but data regarding its safety and efficacy in ACS patients are limited . METHODS In a double-blind , r and omized controlled trial , we compared the safety and efficacy of 8 weeks of treatment with bupropion slow-release ( SR ) or placebo for smokers hospitalized with ACS as an adjunct to nurse-led hospital- and telephone-based support . Primary efficacy outcome was smoking abstinence at 1 year . Primary safety outcome was clinical events at 1 year . RESULTS A total of 151 patients were enrolled ; all but 2 completed follow-up . Abstinence rates at 3 months were 45 % and 44 % in the bupropion SR and placebo groups , respectively ( P = .99 ) ; 37 % vs 42 % ( P = .61 ) at 6 months ; and 31 % vs 33 % ( P = .86 ) at 1 year . On multivariate analysis , an invasive procedure performed during index hospitalization was an independent predictor for smoking abstinence at 1 year ( odds ratio [ OR ] , 4.2 ; 95 % confidence interval [ CI ] , 1.22 - 14.19 ) . Presence of adverse effects attributed to treatment was a negative predictor for smoking cessation ( OR , 0.23 ; 95 % CI , 0.07 - 0.78 ) . Treatment with bupropion SR was not associated with an increase in clinical events or change in blood pressure or body mass index , but dizziness was more common compared with placebo ( 14 % vs 1.4 % ; P = .005 ) . CONCLUSION In hospitalized patients with ACS who received continuous , intensive nurse counseling about smoking cessation , bupropion did not increase the rates of smoking abstinence Objective To test the efficacy of nortriptyline plus nicotine replacement therapy compared with placebo plus nicotine replacement therapy for smoking cessation . Design Pragmatic r and omised controlled trial . Setting National Health Service stop smoking service clinics . Participants 901 people trying to stop smoking . Interventions Participants chose their nicotine replacement product , including combinations of nicotine replacement therapy , and received behavioural support . Nortriptyline was started one to two weeks before quit day , with the dose increased from 25 mg to 75 mg daily for eight weeks and reduced if not tolerated . Main outcome measures Primary outcome was prolonged confirmed abstinence at six months . Secondary outcomes were prolonged abstinence at 12 months , drug use , severity of side effects , nicotine withdrawal symptoms , and urges to smoke . Results 72 of 445 ( 16 % ) people using nortriptyline and 55 of 456 ( 12 % ) using placebo achieved prolonged abstinence at six months ( relative risk 1.34 , 95 % confidence interval 0.97 to 1.86 ) . At 12 months the corresponding values were 49 ( 11 % ) for nortriptyline and 40 ( 9 % ) for placebo ( 1.26 , 0.84 to 1.87 ) . 337 ( 79 % ) people in the nortriptyline arm and 325 ( 75 % ) in the placebo arm were taking combination treatment on quit day , median 75 mg per day in both groups . More people in the nortriptyline arm than in the placebo arm took lower doses . The nortriptyline arm had noticeably higher severity ratings for dry mouth and constipation than the placebo arm , with slightly higher ratings for sweating and feeling shaky . Both groups had similar urges to smoke , but nortriptyline reduced depression and anxiety . Overall , withdrawal symptom scores did not differ . Conclusions Nortriptyline and nicotine replacement therapy are both effective for smoking cessation but the effect of the combination is less than either alone and evidence is lacking that combination treatment is more effective than either alone . Trial registration Current Controlled Trials IS RCT N57852484 This study evaluated the relationship between smoking cessation treatment outcome and the DRD2 polymorphism . Participants were 134 smokers who took part in a larger clinical trial evaluating the effects of an antidepressant medication ( venlafaxine or placebo ) plus st and ard care ( brief counseling and nicotine replacement therapy ) . Venlafaxine is an antidepressant that inhibits the reuptake of serotonin and norepinephrine . A1 smokers were expected to quit significantly less often on placebo , although the abstinence rates between A1s and A2s on active drug were not expected to differ ( i.e. , an interaction between genotype and drug was hypothesized ) . In addition , antidepressant therapy was expected to have a similar genotype x treatment interaction on negative affect reduction . The results showed that smokers carrying the DRD2 A1 allele ( A1/A1/A2 ) quit significantly less often than the homozygous A2s ( OR=1.54 , 95 % CI=1.01 - 2.36 ) . No interaction with treatment was observed . A significant pharmacogenetic effect of the drug on negative mood while quitting also was noted . Smokers absent the A1 allele ( A2/A2 ) responded to the drug with a substantial reduction in negative affect , whereas those with the A1 allele showed no significant reduction in negative mood , F(1 , 130)=5.95 , p=.01 . These results are contrary to expectations and suggest that although A1s may have more difficulty quitting , adding venlafaxine does not improve abstinence or mood . However , the results for the A2s provide evidence for a genotype-specific response to a pharmacological intervention , which could have implication s for the development of future treatments Background The use of spirometry for early detection of chronic obstructive pulmonary disease ( COPD ) is still an issue of debate , particularly because of a lack of convincing evidence that spirometry has an added positive effect on smoking cessation . We hypothesise that early detection of COPD and confrontation with spirometry for smoking cessation may be effective when applying an approach we have termed " confrontational counselling " ; a patient-centred approach which involves specific communication skills and elements of cognitive therapy . An important aspect is to confront the smoker with his/her airflow limitation during the counselling sessions . The primary objective of this study is to test the efficacy of confrontational counselling in comparison to regular health education and promotion for smoking cessation delivered by specialized respiratory nurses in current smokers with previously undiagnosed mild to moderate airflow limitation . Methods / Design The study design is a r and omized controlled trial comparing confrontational counselling delivered by a respiratory nurse combined with nortriptyline for smoking cessation ( experimental group ) , health education and promotion delivered by a respiratory nurse combined with nortriptyline for smoking cessation ( control group 1 ) , and " care as usual " delivered by the GP ( control group 2 ) . Early detection of smokers with mild to moderate airflow limitation is achieved by means of a telephone interview in combination with spirometry . Due to a comparable baseline risk of airflow limitation and motivation to quit smoking , and because of the st and ardization of number , duration , and scheduling of counselling sessions between the experimental group and control group 1 , the study enables to assess the " net " effect of confrontational counselling . The study has been ethically approved and registered . Discussion Ethical as well as method ological considerations of the study are discussed in this protocol . A significant and relevant effect of confrontational counselling would provide an argument in favour of early detection of current smokers with airflow limitation . Successful treatment of tobacco dependence in respiratory patients requires repeated intensive interventions . The results of this study may also show that respiratory nurses are able to deliver this treatment and that intensive smoking cessation counselling is more feasible . Trial registration : Netherl and s Trial Register ( IS RCT N 64481813 ) PURPOSE To determine whether sustained-release bupropion promotes smoking reduction leading to smoking cessation among persons who wish to reduce their amount of smoking , but who are unwilling to quit or who perceive themselves as being unable to quit . METHODS Current smokers were assigned r and omly to receive either sustained-release bupropion ( 150 mg twice daily ) or matching placebo . During an initial 6-month smoking reduction phase , those who were willing to quit entered a 7-week cessation phase , during which study medication was continued . RESULTS Four-week continuous abstinence rates were 14 % ( 41/295 ) in the bupropion group and 8 % ( 25/299 ) in the placebo group ( P = 0.02 ) during treatment . However , this benefit did not continue after treatment was stopped ; subsequent continuous abstinence rates were 7 % ( 20/295 ) in the bupropion group and 5 % ( 16/299 ) in the placebo group ( P = 0.50 ) . Similar proportions of subjects entered the cessation phase in both treatment groups ( 38 % [ n = 113 ] of those in the bupropion group and 34 % [ n = 101 ] of those in the placebo group ) , although the time until a cessation attempt was shorter for those taking bupropion ( median , 64 days vs. 118 days , P = 0.008 ) . The extent of smoking reduction ( measured by urinary cotinine concentrations ) among the 327 subjects who did not enter the cessation phase was significantly greater ( P < 0.05 ) in those treated with bupropion during the reduction treatment phase , but not during the month 12 follow-up visit ( P = 0.25 ) . CONCLUSION Sustained-release bupropion , when used in smokers initially not willing to make a cessation attempt , can help sustain smoking reduction while subjects are on active medication , reduce the time until the next cessation attempt , and increase short-term abstinence rates . However , these benefits were modest and not sustained after bupropion was discontinued OBJECTIVE Evidence that major depression can be a significant hindrance to smoking cessation prompted this examination of the usefulness of sertraline as a cessation aid for smokers with a history of major depression . Specifically , sertraline 's efficacy for smoking abstinence and its effects on withdrawal symptoms were evaluated . METHOD The study design included a 1-week placebo washout , a 9-week double-blind , placebo-controlled treatment phase followed by a 9-day taper period , and a 6-month drug-free follow-up . One hundred thirty-four smokers with a history of major depression were r and omly assigned to receive sertraline ( N=68 ) or matching placebo ( N=66 ) ; all received intensive individual cessation counseling during nine clinic visits . RESULTS Sertraline treatment produced a lower total withdrawal symptom score and less irritability , anxiety , craving , and restlessness than placebo . However , the abstinence rates did not significantly differ between treatment groups : 28.8 % ( 19 of 66 ) for placebo and 33.8 % ( 23 of 68 ) for sertraline at the end of treatment and 16.7 % ( 11 of 66 ) for placebo and 11.8 % ( eight of 68 ) for sertraline at the 6-month follow-up . No moderating effects of single or recurrent major depression , depressed mood at baseline , nicotine dependence level , or gender were observed . CONCLUSIONS Sertraline did not add to the efficacy of an intensive individual counseling program in a double-blind , placebo-controlled study . However , given that the end-of-treatment abstinence rate for the placebo group was much higher than expected , it is unclear whether a ceiling effect of the high level of psychological intervention received by all subjects prevented an adequate test of sertraline Background and aims Bupropion was introduced for smoking cessation following a pivotal trial showing that it gave improved efficacy over the nicotine patch and also suggesting combination treatment was beneficial . We tested in clinical practice for an effectiveness difference between bupropion and nicotine replacement therapy ( NRT ) , whether the combination improves effectiveness and whether either treatment might be more beneficial for certain subgroups of smokers . Design Open-label r and omized controlled trial with 6-month follow-up . Setting Four UK National Health Service ( NHS ) smoking cessation clinics . Participants Smokers ( n = 1071 ) received seven weekly behavioural support sessions and were r and omized to an NRT product of their choice ( n = 418 ) , bupropion ( n = 409 ) or NRT plus bupropion ( n = 244 ) . Measures The primary outcome was self-reported cessation over 6 months , with biochemical verification at 1 and 6 months . Also measured were baseline demographics , health history , smoking characteristics and unwanted events during treatment . Findings Abstinence rates for bupropion ( 27.9 % ) and NRT ( 24.2 % ) were not significantly different ( odds ratio = 1.21 , 95 % confidence interval = 0.883–1.67 ) , and the combination rate ( 24.2 % ) was similar to that for either treatment alone . There was some evidence that the relative effectiveness of bupropion and NRT differed according to depression ( χ2 = 2.86 , P = 0.091 ) , with bupropion appearing more beneficial than NRT in those with a history of depression ( 29.8 versus 18.5 % ) . Several unwanted symptoms were more common with bupropion . Conclusion There is no difference in smoking cessation effectiveness among bupropion , nicotine replacement therapy and their combination when used with behavioural support in clinical practice . There is some evidence that bupropion is more beneficial than nicotine replacement therapy for smokers with a history of depression Background This study evaluates differences in smoking abstinence between white and minority smokers using pharmaceutical aids . Methods This is an analysis of data from a multi-center , r and omized , clinical trial conducted in the United States . Of the 1,684 subjects r and omized to one of three medications ( nicotine inhaler , bupropion , or a combination of both ) , 60 % were women and 10 % were minority races . Results Factors associated with a decreased likelihood of smoking at 12 weeks were older age ( OR = 0.971 , p < 0.0001 ) , being married ( OR = 0.678 , p = 0.0029 ) , using bupropion SR ( OR = 0.480 , p < 0.0001 ) , and using combination therapy ( OR = 0.328 , p < 0.0001 ) . Factors associated with an increased likelihood of smoking were higher tobacco dependence scores ( OR = 1.244 , p < 0.0001 ) , prior quit attempts ( OR = 1.812 , p = 0.004 ) , and being a minority ( OR = 1.849 , p = 0.0083 ) . Compared to white smokers , minority smokers were significantly older at time of study entry ( 46 vs. 42 years , p < 0.0001 ) , less likely to be married ( 35 % vs. 59 % , p < 0.0001 ) , older at smoking initiation ( 21 vs. 19 years of age , p < 0.0001 ) , and had a lower abstinence rate ( 16 % vs. 26 % , p = 0.0065 ) . Conclusion Regardless of the treatment used , minority smokers in the US have lower smoking abstinence after treatment for tobacco dependence . Future research should focus on the improvement in treatment strategies for minority smokers Rationale Monoamine oxidase B ( MAO-B ) activity is reduced in smokers . A MAO-B inhibitor alone or co-administered with nicotine may mimic the effects of smoking and be a c and i date drug for smoking cessation . Objective This study aims to determine the efficacy and safety of EVT302 , a selective reversible MAO-B inhibitor , alone and on top of nicotine patch ( NP ) in smoking cessation . Methods This was a r and omised , double blind , placebo-controlled phase II , multicentre trial . Smokers ( ≥10 cigarettes/day ) received either EVT302 ( N = 145 ) or placebo ( N = 145 ) , or EVT302 ( N = 61 ) or placebo ( N = 61 ) on top of open label NP 21 mg/day for 8 weeks . The main comparison was between EVT302 and placebo without NP . The primary outcome measure was end-of-treatment 4-week continuous abstinence rate ( CAR ) . Secondary outcome measures : point prevalence abstinence rate , saliva cotinine concentrations in the groups without NP , urge to smoke , nicotine withdrawal symptoms and assessment of subjective effects of cigarettes . Results The 4-week CAR was 15.2 % in the placebo , 17.2 % in the EVT302 , 26.8 % in the NP + placebo and 32.8 % in the NP + EVT302 groups , respectively . There was no difference between EVT302 and placebo either alone ( adjusted OR : 1.45 , 95 % CI : 0.65–3.26 ) or when co-administered with NP . No statistically significant difference occurred for the secondary outcome measures . Conclusions The selective , reversible MAO-B inhibitor EVT302 was not superior to placebo in helping smokers quit , in line with data with selegiline and confirms that MAO-B inhibitors are not effective in smoking cessation . Co-administration of NP does not provide a supplementary benefit Smokers ( ⩾10 cigarettes per day , N=331 ) of European ancestry taking part in a double-blind placebo-controlled r and omized trial of 12 weeks of treatment with bupropion along with counseling for smoking cessation were genotyped for a variable number of t and em repeats polymorphism in exon III of the dopamine D4 receptor gene . Generalized estimating equations predicting point-prevalence abstinence at end of treatment and 2 , 6 and 12 months after the end of treatment indicated that bupropion ( vs placebo ) predicted increased odds of abstinence . The main effect of Genotype was not significant . A Genotype × Treatment interaction ( P=0.005 ) showed that bupropion predicted increased odds of abstinence in long-allele carriers ( odds ratios (OR)=1.31 , P<0.0001 ) , whereas bupropion was not associated with abstinence among short-allele homozygotes ( OR=1.06 , P=0.23 ) . The Genotype × Treatment interaction remained when controlling for demographic and clinical covariates ( P=0.01 ) and in analyses predicting continuous abstinence ( P's⩽0.054 ) . Bupropion may be more efficacious for smokers who carry the long allele , which is relevant to personalized pharmacogenetic treatment approaches BACKGROUND African Americans have higher tobacco-related morbidity and mortality and are more likely to smoke menthol cigarettes than their white counterparts . This study examined differences between African American menthol and non-menthol smokers in smoking characteristics and cessation . METHODS The study sample consisted of 600 African American smokers enrolled in a clinical trial that assessed the efficacy of sustained-release bupropion for smoking cessation . Menthol ( n = 471 ) and non-menthol ( n = 129 ) smokers were compared on smoking-related characteristics and abstinence rates at 6 weeks and 6 months . RESULTS Menthol smokers were younger ( 41.2 versus 52.9 years ) , more likely to be female ( 73.7 % versus 56.6 % ) and more likely to smoke their first cigarette within 30 minutes of waking up ( 81.7 % versus 69.8 % ) compared to non-menthol smokers ( all P < 0.01 ) . Cigarette taste ( 50 % versus 40 % , P = 0.054 ) was rated non-significantly higher by menthol smokers . Seven-day point-prevalence abstinence from smoking at 6 weeks were 28 % and 42 % ( P = 0.006 ) and at 6 months were 21 % and 27 % ( P = 0.21 ) for menthol and non-menthol smokers , respectively . At 6 weeks follow-up , stepwise logistic regression revealed that among those younger than 50 years , non-menthol smokers were more likely to quit smoking ( odds ratio = 2.0 ; 95 % CI = 1.03 - 3.95 ) as were those who received bupropion ( odds ratio = 2.12 ; 95 % CI = 1.32 - 3.39 ) . CONCLUSION African American menthol smokers had lower smoking cessation rates after 6 weeks of treatment with bupropion-SR , thereby putting menthol smokers at greater risk from the health effects of smoking . Lower overall cessation rates among African Americans menthol smokers may partially explain ethnic differences in smoking-related disease risks Although the efficacy of pharmacotherapy for tobacco dependence has been previously demonstrated , there is substantial variability among individuals in treatment response . We performed a systems-based c and i date gene study of 1295 single nucleotide polymorphisms ( SNPs ) in 58 genes within the neuronal nicotinic receptor and dopamine systems to investigate their role in smoking cessation in a bupropion placebo-controlled r and omized clinical trial . Putative functional variants were supplemented with tagSNPs within each gene . We used global tests of main effects and treatment interactions , adjusting the P-values for multiple correlated tests . An SNP ( rs2072661 ) in the 3′ UTR region of the β2 nicotinic acetylcholine receptor subunit ( CHRNB2 ) has an impact on abstinence rates at the end of treatment ( adjusted P = 0.01 ) and after a 6-month follow-up period ( adjusted P = 0.0002 ) . This latter P-value is also significant with adjustment for the number of genes tested . Independent of treatment at 6-month follow-up , individuals carrying the minor allele have substantially decreased the odds of quitting ( OR = 0.31 ; 95 % CI 0.18–0.55 ) . Effect of estimates indicate that the treatment is more effective for individuals with the wild-type ( OR = 2.14 , 95 % CI 1.20–3.81 ) compared with individuals carrying the minor allele ( OR = 0.83 , 95 % CI 0.32–2.19 ) , although this difference is only suggestive ( P = 0.10 ) . Furthermore , this SNP demonstrated a role in the time to relapse ( P = 0.0002 ) and an impact on withdrawal symptoms at target quit date ( TQD ) ( P = 0.0009 ) . Overall , while our results indicate strong evidence for CHRNB2 in ability to quit smoking , these results require replication in an independent sample Despite effective therapies for smoking cessation , most smokers find quitting difficult and most successful quitters relapse . Considerable evidence supports a genetic risk for nicotine dependence ; however , less is known about the pharmacogenetics of smoking cessation . In the first pharmacogenetic investigation of the efficacy of varenicline and bupropion , we examined whether genes important in the pharmacodynamics and pharmacokinetics of these drugs and nicotine predict medication efficacy and adverse events . Subjects participated in r and omized , double-blind , placebo-controlled smoking cessation clinical trials , comparing varenicline , a nicotinic acetylcholine receptor ( nAChR ) partial agonist , with bupropion , a norepinephrine/dopamine reuptake inhibitor , and placebo . Primary analysis included 1175 smokers of European ancestry , and 785 single nucleotide polymorphisms from 24 genes , representing 254 linkage disequilibrium ( LD ) bins ( genes included nAChR subunits , additional varenicline-specific genes , and genes involved in nicotine or bupropion metabolism ) . For varenicline , continuous abstinence ( weeks 9–12 ) was associated with multiple nAChR subunit genes ( including CHRNB2 , CHRNA5 , and CHRNA4 ) ( OR=1.76 ; 95 % CI : 1.23–2.52 ) ( p<0.005 ) ; for bupropion , abstinence was associated with CYP2B6 ( OR=1.78 ; 95 % CI : 1.27–2.50 ) ( p<0.001 ) . Incidence of nausea was associated with several nAChR subunit genes ( OR=0.50 ; 95 % CI : 0.36–0.70 ) ( p<0.0001 ) and time to relapse after quitting was associated with HTR3B ( HR=1.97 ; 95 % CI : 1.45–2.68 ) ( p<0.0001 ) . These data provide evidence for multiple genetic loci contributing to smoking cessation and therapeutic response . Different loci are associated with varenicline vs bupropion response , suggesting that additional research may identify clinical ly useful markers to guide treatment decisions The study was a r and omized placebo-controlled trial testing whether fluoxetine selectively enhances cessation for smokers with a history of depression . Euthymic smokers with ( H+ , n = 109 ) or without ( H- , n = 138 ) a history of major depression received 60 mg fluoxetine or placebo plus group behavioral quit-smoking treatment for 12 weeks . Fluoxetine initially enhanced cessation for H+ smokers ( p = .02 ) but subsequently impaired cessation regardless of depressive history . Six months after quit date , fluoxetine-treated participants were 3.3 times more likely to be smoking ( p = .02 ) . Further research is warranted to determine why high-dose fluoxetine produces continuing effects that oppose tobacco abstinence Aim To evaluate the efficacy of nortriptyline ( NOR ) added to a multi-component smoking cessation intervention , which included cognitive – behavioural therapy ( CBT ) and provision of nicotine replacement therapy ( NRT ) . Design R and omized controlled trial ( RCT ) comparing two study groups with blinded follow-up at 3 , 6 and 12 months . Both groups received a multi-component smoking cessation intervention comprising two half-hour individual sessions of CBT and NRT with either active NOR or placebo . Setting Prisons in New South Wales ( 17 ) and Queensl and ( one ) , Australia . Participants A total of 425 male prisoners met inclusion criteria and were allocated to either treatment ( n = 206 ) or control group ( n = 219 ) . Measurements Primary end-points at 3 , 6 and 12 months were continuous abstinence , point prevalence abstinence and reporting a 50 % reduction in smoking . Smoking status was confirmed by expired carbon monoxide , using a cut-point of ≤10 parts per million . Findings Participants ' demographics and baseline tobacco use were similar in treatment and control groups . Based on an intention-to-treat analysis , continuous abstinence between the treatment and control groups was not significantly different at 3 months ( 23.8 versus 16.4 % ) , 6 months ( 17.5 versus 12.3 % ) and 12 months ( 11.7 versus 11.9 % ) . Conclusion Adding nortriptyline to a smoking cessation treatment package consisting of behavioural support and nicotine replacement therapy does not appear to improve long-term abstinence rates in male prisoners The purpose of this study was to investigate the effect of adding sustained-release ( SR ) bupropion to cognitive behavioral therapy ( CBT ) on smoking behavior and stability of psychiatric symptoms in patients with schizophrenia . We conducted a 3-month , double-blind , placebo-controlled trial of bupropion SR , 150 mg/day , added to a concurrent CBT program with 3-month follow-up in 19 stable out patients with schizophrenia who wanted to quit smoking . Eighteen subjects completed the trial . Bupropion treatment was associated with significantly greater reduction in smoking , as measured by self-report verified by expired-air carbon monoxide ( 6/9 subjects , 66 % ) , than placebo ( 1/9 subjects , 11 % ) during the 3-month active treatment period and the 3-month follow-up period . One subject in the bupropion group ( 11 % ) and no subjects in the placebo group achieved sustained tobacco abstinence for the 6-month trial . Bupropion treatment was associated with improvement in negative symptoms and greater stability of psychotic and depressive symptoms , compared with placebo , during the quit attempt . Subjects in the bupropion group experienced significant weight loss , compared with those on placebo during the smoking cessation attempt . These data suggest that bupropion SR , 150 mg/day , combined with CBT , may facilitate smoking reduction in patients with schizophrenia while stabilizing psychiatric symptoms during a quit attempt In this study , 147 smokers were r and omly assigned to receive either venlafaxine or placebo in conjunction with behavioral counseling ( 9 weekly sessions ) and transdermal nicotine replacement therapy ( 22 mg/day ) . Patients began medication 2 weeks before quitting and continued for 18 weeks after quitting , with the daily dose titrated from 150 to 225 mg . in response to symptoms of negative affect and relapse . The results showed no main effect of treatment on abstinence . Post hoc analysis revealed that both at the end of treatment and at the 1-year follow-up smokers consuming less than a pack of cigarettes a day benefited from the addition of venlafaxine to the treatment regimen . Venlafaxine also reduced negative affect for all smokers for up to 6 weeks postcessation . The findings suggest that venlafaxine could have some role to play in the treatment of lighter smokers , in addition to the expected benefits of nicotine replacement therapy and behavioral counseling BACKGROUND Several studies have shown an association between smoking and major depressive disorder ( MDD ) , but few have prospect ively examined subjects who develop MDD after quitting smoking . This descriptive study evaluated the development of MDD after smoking cessation , as assessed by a structured clinical interview at both baseline and the end of treatment . METHOD Nondepressed participants ( N = 114 ) in a trial investigating the effect of fluoxetine on smoking cessation were administered the Structured Clinical Interview for DSM-III-R at baseline and posttreatment to evaluate the impact of quitting smoking on the development of MDD . Depressive symptoms were additionally assessed with the Beck Depression Inventory and the Hamilton Rating Scale for Depression . RESULTS At baseline , 32 % of the subjects reported a history of MDD . Sixty-nine subjects completed the SCID at baseline and posttreatment . At posttreatment , 5 subjects ( 7 % ) met threshold criteria for MDD ; none were taking the highest dose of fluoxetine ( 60 mg ) , 4 were taking 30 mg , and 1 was taking placebo . All 5 had a history of MDD ; 3 were women . Four had a history of substance abuse and attained at least 3 consecutive biochemically verified weeks of smoking abstinence . Those who developed MDD after treatment scored significantly higher on measures of depressed mood at baseline than those who did not develop MDD after smoking-cessation treatment . CONCLUSION The results from this descriptive study suggest that a subset of smokers may be at risk for developing MDD after smoking cessation Cigarette smoking is prevalent in cocaine/methamphetamine-dependent patients and associated with significant morbidity and mortality , yet , the provision of smoking cessation treatment in conjunction with substance use disorder ( SUD ) treatment is not st and ard practice . This is due , in part , to clinician concern that combining smoking cessation treatment with SUD treatment could lead to poorer SUD outcomes . The NIDA Clinical Trials Network is conducting a 10-week , two-group , r and omized trial to evaluate the impact of providing smoking cessation treatment ( SCT ) with SUD treatment as usual ( TAU ) , compared to TAU alone , in smokers who are in outpatient treatment for cocaine or methamphetamine dependence . Approximately 528 participants , recruited from 12 community treatment programs , will be r and omized into the trial . The present paper describes key design decisions made during protocol development . The trial is design ed to evaluate the relationship between cigarette smoking and stimulant use , which prior research suggests is linked , and should contribute to our underst and ing of how best to address the co-occurring problems of nicotine dependence and cocaine/methamphetamine-dependence . Unique aspects of the trial include the primary question of interest , which concerns the impact of providing SCT on SUD outcomes rather than on smoking outcomes , and the intensity of the SCT chosen , which includes bupropion , nicotine replacement , and two psychosocial interventions CONTEXT African Americans disproportionately experience greater smoking attributable morbidity and mortality . Few clinical trials for smoking cessation in African Americans have been conducted , despite a different profile of both smoking and quitting patterns . OBJECTIVE To compare a sustained-release form of bupropion hydrochloride ( bupropion SR ) with placebo for smoking cessation among African Americans . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial conducted from February 11 , 1999 , to December 8 , 2000 , of 600 African American adults treated at a community-based health care center . Volunteers , who smoked 10 or more cigarettes per day were recruited by targeted media and health care professionals . INTERVENTION Participants were r and omly assigned to receive 150 mg of bupropion SR ( n = 300 ) or placebo ( n = 300 ) twice daily for 7 weeks . Brief motivational counseling was provided in-person at baseline , quit day , weeks 1 and 3 , end of treatment ( week 6 ) , and by telephone at day 3 and weeks 5 and 7 . MAIN OUTCOME MEASURES Biochemically confirmed 7-day point prevalence abstinence at weeks 6 and 26 following quit day . RESULTS Using intention-to-treat procedures , confirmed abstinence rates at the end of 7 weeks of treatment were 36.0 % in the bupropion SR group and 19.0 % in the placebo group ( 17.0 percentage point difference ; 95 % confidence interval , 9.7 - 24.4 ; P<.001 ) . At 26 weeks the quit rates were 21.0 % in the treatment and 13.7 % in the placebo groups ( 7.3 percentage point difference ; 95 % confidence interval , 1.0 - 13.7 ; P = .02 ) . Those taking bupropion SR experienced a greater mean reduction in depression symptoms at week 6 ( 2.96 [ 9.45 ] vs 1.13 [ 8.84 ] ) than those taking placebo , and after controlling for continuous abstinence , those taking bupropion SR also gained less weight than those taking placebo . CONCLUSIONS Bupropion SR was effective for smoking cessation among African Americans and may be useful in reducing the health disparities associated with smoking The aim was to evaluate if recycling of failures from a smoking cessation study may be of value . The study comprised 126 smokers ( 50 % ) of 252 failures , from a double-blind smoking cessation trial with nicotine patch , who accepted recycling after 1 year . Subjects were allocated nicotine patches delivering 15 , 20 or 25 mg of nicotine ( over 16 hours ) according to their base-line saliva cotinine concentrations in an open trial . The treatment period was 12 weeks followed by tapering over 6 weeks . The percentage of quitters after 3 , 12 , 26 , and 52 weeks was 44 , 20 , 7 and 6 % , respectively . After 26 weeks , all subjects had relapsed in the group previously treated with active nicotine patch compared with 12 % abstainers in the previous placebo subjects . The sustained abstinence rate without slips after one year was 2 % . Recycling does not seem to be of long-term clinical relevance in our set-up for subjects initially treated with nicotine , but of some value in subjects quitting without nicotine therapy initially BACKGROUND Long-term success rates of smoking cessation programs for patients with schizophrenia are unknown . This study , conducted between June 2001 and November 2002 , evaluated the rate of smoking cessation and reduction in patients with schizophrenia ( DSM-IV ) 2 years after they had participated in a smoking cessation study in order to determine whether subjects who significantly reduced smoking during the original trial resumed their previous level of smoking at 2 years . METHOD Two years following a double-blind placebo-controlled trial of bupropion sustained release , 150 mg/day , added to cognitive-behavioral therapy for smoking cessation in patients with schizophrenia , subjects were interviewed , medical charts were review ed , and carbon monoxide in expired air was measured . RESULTS Seventeen of 18 subjects completed the follow-up assessment . More subjects were abstinent ( 22 % [ N = 4 ] ) at the 2-year follow-up than were abstinent at the end of the trial ( 6 % [ N = 1 ] ) . Subjects who achieved significant smoking reduction during the trial were more likely to be abstinent at 2 years ( 4/7 ) than those who did not significantly reduce smoking during the trial ( 0/11 ) ( chi(2 ) = 8.1 , p < .005 ) . Most subjects who achieved > or = 50 % reduction in smoking at the end of the trial maintained at least that level of reduction at 2 years . Smoking reduction during the treatment intervention was correlated with smoking reduction at follow-up ( r = 0.60 , p = .01 ) . CONCLUSION The results from this naturalistic study suggest that behavior changes achieved in smoking cessation programs for patients with schizophrenia may be durable and may predict future smoking behavior . We conclude that further investigation into the relationship between smoking reduction and future smoking cessation in special population s is indicated BACKGROUND Cigarette smoking has been associated with increases in C-reactive protein ( CRP ) and leukocyte counts ( white blood cell [ WBC ] ) ; however , the effects of smoking intensity and smoking cessation on inflammatory markers have not been evaluated prospect ively in a large , modern cohort of current smokers . METHODS White blood cell count and high-sensitivity CRP were measured in current smokers enrolled in a r and omized , prospect i ve clinical trial of 5 smoking cessation pharmacotherapies . Smoking intensity parameters included cigarettes per day , pack-years , Fagerström Test of Nicotine Dependence score , and carbon monoxide levels . C-reactive protein also was measured after 1 year with assessment of abstinence status . RESULTS The 1,504 current smokers ( 58 % female ) were ( mean [ SD ] ) 44.7 ( 11.1 ) years old , smoked 21.4 ( 8.9 ) cigarettes per day , and had a smoking burden of 29.4 ( 20.4 ) pack-years . Log(CRP ) was not associated with any marker of smoking intensity , except for a weak correlation with pack-years ( r = 0.05 , P = .047 ) . In contrast , statistically significant correlations were observed between all 4 markers of smoking intensity and WBC count ( all P ≤ .011 ) . In multivariable models , waist circumference ( P < .001 ) and triglycerides ( P < .05 ) , but no markers of smoking intensity , were associated with log(CRP ) . However , pack-years ( P = .002 ) , cigarettes per day ( P = .013 ) , carbon monoxide ( P < .001 ) , and Fagerström Test of Nicotine Dependence ( P < .001 ) were independently associated with WBC count . After 1 year , log(CRP ) ( P = .296 ) and changes in log(CRP ) ( P = .455 ) did not differ between abstainers and continuing smokers . CONCLUSIONS Smoking intensity is associated with increased WBC count , but not CRP levels . Smoking cessation does not reduce CRP . The relationship between CRP and smoking intensity may be masked by CRP 's stronger relationship with adiposity Bupropion is an antidepressant shown to be efficacious for smoking cessation . This study examined the short- and long-term effects of bupropion ( 300 mg/day for 10 weeks ) versus placebo on depression symptoms among 497 smokers attempting to quit in a r and omized trial of bupropion plus behavioral counseling . Depression symptoms were assessed via the Center for Epidemiological Studies Depression Scale ( L. Radloff , 1977 ) at baseline , end of treatment , and at 6-month follow-up . Baseline nicotine dependence level was assessed with the Fagerström Test for Nicotine Dependence ( T. F. Heatherton , L. T. Kozlowski , R. C. Frecker , & K. O. Fagerstrom , 1991 ) . A regression model of depression symptoms demonstrated a significant interaction between nicotine dependence and treatment for the treatment phase and during follow-up . Depression symptoms did not mediate the effects of bupropion on abstinence at either time point . Highly nicotine-dependent smokers who receive bupropion are more likely to experience a decrease in depressive symptoms during active treatment but are also more likely to experience a rebound in depressive symptoms when bupropion is discontinued Abstract Gestational smoking has been established as a risk to the fetus . However , many pregnant smokers are unable to quit due to the highly addictive nature of nicotine . Nicotine replacement therapy has failed in several studies in pregnant women . In a prospect i ve matched , controlled observational study , of 22 pregnant smokers receiving bupropion , 10 ( 45 % ) ceased smoking , as compared to 3 ( 14 % ) of 22 controls ( p = 0.047 ) . Bupropion appears to be effective for smoking cessation therapy during pregnancy BACKGROUND We previously documented that cognitive behavioral therapy for smoking-related weight concerns ( CONCERNS ) improves cessation rates . However , the efficacy of combining CONCERNS with cessation medication is unknown . We sought to determine if the combination of CONCERNS and bupropion therapy would enhance abstinence for weight-concerned women smokers . METHODS In a r and omized , double-blind , placebo-controlled trial , weight-concerned women ( n = 349 ; 86 % white ) received smoking cessation counseling and were r and omized to 1 of 2 adjunctive counseling components : CONCERNS or ST AND ARD ( st and ard cessation treatment with added discussion of smoking topics but no specific weight focus ) , and 1 of 2 medication conditions : bupropion hydrochloride sustained release ( B ) or placebo ( P ) for 6 months . Rates and duration of biochemically verified prolonged abstinence were the primary outcomes . Point-prevalent abstinence , postcessation weight gain , and changes in nicotine withdrawal , depressive symptoms , and weight concerns were evaluated . RESULTS Women in the CONCERNS + B group had higher rates of abstinence ( 34.0 % ) and longer time to relapse than did those in the ST AND ARD + B ( 21 % ; P = .05 ) or CONCERNS + P ( 11.5 % ; P = .005 ) groups at 6 months , although rates of prolonged abstinence in the CONCERNS + B and ST AND ARD + B groups did not differ significantly at 12 months . Abstinence rates and duration did not differ in the ST AND ARD + B group ( 21 % and 19 % ) compared with the ST AND ARD + P group ( 10 % and 7 % ) at 6 and 12 months , respectively . There were no differences among abstinent women in postcessation weight gain or weight concerns , although ST AND ARD + B produced greater decreases in nicotine withdrawal and depressive symptoms than did ST AND ARD + P. CONCLUSIONS Weight-concerned women smokers receiving the combination of CONCERNS + B were most likely to sustain abstinence . This effect was not related to differences in postcessation weight gain or changes in weight concerns . Trial Registration clinical trials.gov Identifier : NCT00006170 Serotonin uptake inhibitors have been reported to alter several consummatory and drug self-administration behaviors in rats . These observations suggest important therapeutic applications in humans . While evaluating zimelidine and citalopram effects on ethanol intake , we also assessed smoking behavior . Five male heavy drinkers smoking 29.7 + /- 9.0 ( mean + /- SD ) cigarettes a day were r and omly allocated to receive zimelidine ( 200 mg/day orally ) or placebo in a double-blind crossover study . Another 17 male heavy drinkers smoking 21.1 + /- 14.3 ( mean + /- SD ) cigarettes a day were r and omly allocated to receive citalopram ( 20 or 40 mg/day orally ) or placebo in a double-blind crossover study . In both studies , subjects were not trying to modify their smoking or drinking and received no advice or other treatment to do so . Zimelidine had no effects on the number of cigarettes smoked ( F1,4 = 1.80 , not significant ( NS ] . Neither citalopram dose had an effect on smoking ( citalopram 20 mg : F1,8 = 0.06 , NS ; citalopram 40 mg : F1,7 = 0.68 , NS ) . Because intrasubject variation is small , this trial was of sufficient size to exclude with 99.99 % confidence the possibility that these drugs decrease smoking behavior by 50 % . Since serotonin uptake inhibitors can attenuate ethanol intake in humans , these drugs may have differential effects on consummatory behaviors Introduction : An employer-based cost-benefit analysis for varenicline versus bupropion was conducted using clinical outcomes from a recently published trial . Methods : A decision tree model was developed based on the net benefit of treatment to produce a nonsmoker at 1 year . Sensitivity analyses were conducted based on quit rates with placebo and varenicline and the cost of varenicline . Results : Estimated 12-month employer cost savings per non-smoking employee were $ 540.60 for varenicline , $ 269.80 for bupropion SR generic , $ 150.80 for bupropion SR br and , and $ 81.80 for placebo . Varenicline was more cost beneficial than placebo , which had quit rates of 16.9 % or less . The quit rate with varenicline would have to be ≤16.9 % to lose cost benefit over bupropion SR generic . Conclusions : The economic benefit of varenicline is improved over bupropion , despite the increased initial cost of varenicline Tobacco withdrawal symptoms hamper smoking cessation . This was a pilot study of buspirone , a new azapirone anxiolytic , for tobacco withdrawal . Thirteen smokers entered an open clinical trial . Smokers were titrated to 30 mg/day of oral buspirone for 2 weeks prior to cessation . Tobacco withdrawal and Spielberger state-anxiety scales were used at baseline , on the quit date , and then at 24 hours , 48 hours , 1 week , and 2 weeks after abrupt cessation . At the final visit , smokers compared their withdrawal experience with previous cessation attempts . Two patients ( 15 percent ) could not tolerate the medication and did not attempt smoking cessation . Of the remaining 11 smokers , 3 ( 27 percent ) rated withdrawal relief “ very definite , ” 6 ( 55 percent ) “ moderate , ” and 2 ( 18 percent ) “ slight . ” More than two-thirds of the smokers believed that their difficulty concentrating , craving , restlessness , and anxiety were improved compared with earlier tobacco withdrawal attempts . Five patients ( 46 percent ) reported decreased smoking urges during the 2-week medication titration period . Tobacco withdrawal symptoms and state-anxiety scores changed significantly during the study ( P < 0.05 ) . These results are encouraging , but they should be interpreted with caution because of the small sample size and lack of placebo control . Buspirone effect on tobacco withdrawal symptoms should be studied in a r and omized , controlled clinical trial Smoking cessation attempts are often complicated by dysphoria/depression , weight gain , craving , and other nicotine withdrawal symptoms . Fluoxetine 's antidepressant and anorectant properties , along with its capacity to attenuate compulsive behavior , suggest that this medication might facilitate smoking cessation treatment . We examined the effect of fluoxetine on smoking cessation in the context of a program that included group cognitive-behavioral therapy ( six weeks ) and transdermal nicotine patch(ten weeks ) . In a double-blind r and omized trial of fluoxetine for smoking cessation , 150 daily smokers were assigned to placebo ( n=48 ) , 20 mg ( n=51 ) , or 40 mg fluoxetine ( n=51 ) . Fluoxetine did not significantly improve smoking cessation rates , either for those with or without major depressive disorder(MDD)histories or elevated current depression . Our results suggest that fluoxetine may moderate withdrawal symptoms , even if that was not manifested in improved smoking cessation rates . Our results , however , clearly favor the use of fluoxetine if weight gain is a major clinical obstacle to smoking cessation Heading Abstract Rationale . Changes in dopamine level are thought to play an important role in both smoking reward and withdrawal symptoms during abstinence . Medications that modulate dopamine levels may have beneficial effects on both withdrawal symptom levels and on response to smoking lapses during abstinence . Objectives . To examine the effects of the selective MAO-B inhibitor selegiline on withdrawal symptoms , smoking behavior and smoking satisfaction ratings . Methods . Fifteen smokers received selegiline ( 10 mg/day ) and placebo ( in counterbalanced order ) on Monday through Thursday of 2 study weeks , separated by a 2-week washout . During each study week , ad lib smoking sessions were scheduled to assess smoking behavior both before and after a brief period of abstinence . Subjective withdrawal symptoms and mood were measured daily , and a modified Stroop test sensitive to withdrawal was scheduled during the period of abstinence . Results . Selegiline decreased craving , especially during abstinence , and impaired performance on the modified Stroop test during subjects ' attempts to abstain . Medication also reduced number of cigarettes smoked and smoking satisfaction ratings during the smoking sessions both before and after the brief abstinence attempt . Conclusion . These results are consistent with an important role of dopamine in smoking behavior and abstinence . They suggest that pharmacological reduction of MAO-B levels during the early part of a quit attempt may aid in smoking cessation AIM To investigate the efficacy of maintenance treatment with bupropion and /or nicotine gum for reducing smoking relapse . DESIGN , SETTING AND PARTICIPANTS A 48-week study was conducted at a university-based smoking cessation clinic between February 2001 and October 2005 . A total of 588 smokers received bupropion and nicotine patch in 8 weeks of open-label treatment ( OLT ) ; 289 abstainers during the last 4 weeks of OLT were r and omized in double-blind placebo-controlled fashion to one of four arms for 16 weeks of maintenance treatment ( MT ) followed by 24 weeks of non-treatment follow-up ( NTFU ) . INTERVENTION Bupropion ( 300 mg/day ) and 2 mg nicotine gum , used alone or combined , and comparable placebo pill and placebo gum . Behavioral counseling at all visits . OUTCOME Time to relapse ( TTR ) from r and omization . Relapse is defined as the first 7 consecutive days of smoking . Abstinence verified by carbon monoxide < or= 8 parts per million . FINDINGS TTR was longer with extended active treatments compared to placebo ( median days to relapse : bupropion + placebo = 136 , nicotine + placebo = 98 , bupropion + nicotine = 90 , double placebo = 71 ) . Hazard ratios ( HR ) for relapse were statistically significant for bupropion + placebo versus double placebo during MT ( HR = 0.59 , 95 % CI = 0.37 - 0.92 ) and to the end of NTFU ( HR = 0.66 , 95 % CI = 0.42 - 0.96 ) . However , bupropion 's advantage dissipated upon stopping the drug . Gum use was low , preventing a valid assessment ; but analysis restricted to gum users suggested a weak effect of extended nicotine gum . CONCLUSION Maintenance treatment with bupropion exerted a modest benefit for preventing smoking relapse ; the optimum duration of bupropion treatment was unclear . Further research is needed to ascertain the merits of extended use of nicotine gum , other nicotine replacement agents and other treatments known to aid smokers for preventing relapse once abstinence is achieved Abstract Rationale and objectives : Bupropion has demonstrated efficacy for smoking cessation . Given the importance of nicotine craving and withdrawal in the smoking cessation process , the current study examined the effects of bupropion on these parameters during smoking abstinence . Methods : During a 2-day Baseline phase with ad lib smoking , 91 non-depressed smokers ( who were not trying to quit permanently ) were administered measures of nicotine craving , withdrawal symptoms , and timed measures of cognitive performance five times daily . Participants were then assigned r and omly to a 14-day treatment regimen with bupropion 300 mg/day , bupropion 150 mg/day , or placebo . Thereafter , the above measures were re-administered during 3 days of abstinence on a closed research ward . Results : Relative to placebo , 300 mg bupropion significantly reduced abstinence-associated increases in rated depression , difficulty concentrating , and irritability , and attenuated a decrease in positive affect . The results also suggested that bupropion might have a positive effect on performance measures during the withdrawal period . No effects were observed on craving , anxiety , restlessness , or hunger . The lack of findings on craving measures may be explained by a floor effect ; except on the first day of abstinence , neither drug nor placebo groups showed much craving elevation during abstinence . Conclusions : Study results indicate that bupropion ameliorates some nicotine withdrawal symptoms AIMS To evaluate the associations of treatment and an additive genetic efficacy score ( AGES ) based on dopamine functional polymorphisms with time to first smoking lapse and point prevalence abstinence at end of treatment among participants enrolled into two r and omized clinical trials of smoking cessation therapies . DESIGN Double-blind pharmacogenetic efficacy trials r and omizing participants to active or placebo bupropion . Study 1 also r and omized participants to cognitive-behavioral smoking cessation treatment ( CBT ) or this treatment with CBT for depression . Study 2 provided st and ardized behavioural support . SETTING Two hospital-affiliated clinics ( study 1 ) , and two university-affiliated clinics ( study 2 ) . PARTICIPANTS A total of 792 self-identified white treatment-seeking smokers aged ≥18 years smoking ≥10 cigarettes per day over the last year . MEASUREMENTS Age , gender , Fagerström Test for Nicotine Dependence , dopamine pathway genotypes ( rs1800497 [ ANKK1 E713 K ] , rs4680 [ COMT V158 M ] , DRD4 exon 3 variable number of t and em repeats polymorphism [ DRD4 VNTR ] , SLC6A3,3 ' VNTR ) analyzed both separately and as part of an AGES , time to first lapse and point prevalence abstinence at end of treatment . FINDINGS Significant associations of the AGES ( hazard ratio [ HR ] = 1.10 , 95 % confidence interval [ CI ] = 1.06 - 1.14 , P = 0.009 ) and of the DRD4 VNTR ( HR = 1.29 , 95 % CI = 1.17 - 1.41 , P = 0.0073 ) were observed with time to first lapse . A significant AGES by pharmacotherapy interaction was observed ( β st and ard error = -0.18 [ 0.07 ] , P = 0.016 ) , such that AGES predicted risk for time to first lapse only for individuals r and omized to placebo . CONCLUSIONS A score based on functional polymorphisms relating to dopamine pathways appears to predict lapse to smoking following a quit attempt , and the association is mitigated in smokers using bupropion AIMS To underst and the relations among anxiety disorders and tobacco dependence , withdrawal symptoms , response to smoking cessation pharmacotherapy and ability to quit smoking . DESIGN R and omized placebo-controlled clinical trial . Participants received six 10-minute individual counseling sessions and either : placebo , bupropion SR , nicotine patch , nicotine lozenge , bupropion SR + nicotine lozenge or nicotine patch + nicotine lozenge . SETTING Two urban research sites . PARTICIPANTS Data were collected from 1504 daily smokers ( > 9 cigarettes per day ) who were motivated to quit smoking and did not report current diagnoses of schizophrenia or psychosis or bupropion use . MEASUREMENTS Participants completed baseline assessment s , the Composite International Diagnostic Interview and ecological momentary assessment s for 2 weeks . FINDINGS A structured clinical interview identified participants who ever met criteria for a panic attack ( n = 455 ) , social anxiety ( n = 199 ) or generalized anxiety disorder ( n = 99 ) , and those who qualified for no anxiety diagnosis ( n = 891 ) . Smokers with anxiety disorders reported higher levels of nicotine dependence and pre-quit withdrawal symptoms . Those ever meeting criteria for panic attacks or social anxiety disorder showed greater quit-day negative affect . Smokers ever meeting criteria for anxiety disorders were less likely to be abstinent at 8 weeks and 6 months post-quit and showed no benefit from single-agent or combination-agent pharmacotherapies . CONCLUSIONS Anxiety diagnoses were common among treatment-seeking smokers and were related to increased motivation to smoke , elevated withdrawal , lack of response to pharmacotherapy and impaired ability to quit smoking . These findings could guide treatment assignment algorithms and treatment development for smokers with anxiety diagnoses AIMS Tobacco dependence treatments achieve abstinence rates of 25 - 30 % at 1 year . Low rates may reflect failure to conceptualize tobacco dependence as a chronic disorder . The aims of the present study were to determine the efficacy of extended cognitive behavioral and pharmacological interventions in smokers > or = 50 years of age , and to determine if gender differences in efficacy existed . DESIGN Open r and omized clinical trial . SETTING A free-st and ing , smoking treatment research clinic . PARTICIPANTS A total of 402 smokers of > or = 10 cigarettes per day , all 50 years of age or older . INTERVENTION Participants completed a 12-week treatment that included group counseling , nicotine replacement therapy ( NRT ) and bupropion . Participants , independent of smoking status , were then assigned r and omly to follow-up conditions : ( i ) st and ard treatment ( ST ; no further treatment ) ; ( ii ) extended NRT ( E-NRT ; 40 weeks of nicotine gum availability ) ; ( iii ) extended cognitive behavioral therapy ( E-CBT ; 11 cognitive behavioral sessions over a 40-week period ) ; or ( iv ) E-CBT plus E-NRT ( E-combined ; 11 cognitive behavioral sessions plus 40 weeks nicotine gum availability ) . MEASUREMENTS Primary outcome variable was 7-day point prevalence cigarette abstinence verified biochemically at weeks 24 , 52 , 64 and 104 . FINDINGS The most clinical ly important findings were significant main effects for treatment condition , time and the treatment x time interaction . The E-CBT condition produced high cigarette abstinence rates that were maintained throughout the 2-year study period [ ( week 24 ( 58 % ) , 52 ( 55 % ) , 64 ( 55 % ) and 104 ( 55 % ) ] , and was significantly more effective than E-NRT and ST across that period . No other treatment condition was significantly different to ST . No effects for gender were found . CONCLUSIONS Extended cognitive behavioral treatments can produce high and stable cigarette abstinence rates for both men and women . NRT does not add to the efficacy of extended CBT , and may hamper its efficacy . Research is needed to determine if these results can be replicated in a sample with a greater range of ages , and improved upon with the addition of medications other than NRT Adults with depression evidence higher rates of smoking and lower quit rates than adults without depression . Little is known about the relationship between depression and smoking beliefs which are associated with both smoking and smoking cessation behavior . The primary aim of this study was to examine whether adult smokers with and without a history of major depressive disorder ( MDD ) differ in their endorsement of smoking expectancies . The secondary aim of the study was to examine whether there were interactions of depression and gender on the endorsement of expectancies . Adult cigarette smokers participating in a clinical trial of Selegiline hydrochloride for smoking cessation were classified as having a history of depression ( MDD+ , n=26 ) or no history of depression ( MDD- , n=75 ) . History of depression and smoking expectancies were assessed prior to r and omization into the clinical trial . There was a main effect of depression on 7 out of 10 of the assessed beliefs . MDD+ smokers , compared to MDD- smokers , more strongly endorsed beliefs that smoking reduces negative affect , boredom , and cravings ; smoking increases stimulation and social facilitation ; smoking helps to manage cravings and weight ; and that the taste is enjoyable . The main effect of gender and the interactive effect of depression and gender were not significant . Incorporating expectancies into cognitive-behavioral treatments for smoking cessation may be useful for smokers with a history of depression This study was conducted to evaluate the effect of bupropion sustained-release ( SR ) on smoking cessation in patients with chronic posttraumatic stress disorder ( PTSD ) . Fifteen veterans with chronic PTSD who desired to stop smoking enrolled in a 12-week double-blind evaluation of bupropion SR and placebo . Patients were r and omly assigned in a 2:1 ratio to receive either bupropion SR or placebo . Bupropion SR was initiated at 150 mg daily for 3 or 4 days and increased to a final dose of 150 mg twice daily ( 300 mg daily total ) . Ten patients received bupropion SR and five received placebo . Nine of the patients who received bupropion SR were already being treated with at least one other psychotropic medication . One of the ten patients did not complete the study because of medication side effects . Eighty percent of patients receiving bupropion SR successfully stopped smoking by the end of week 2 , and 6 ( 60 % ) of these 10 maintained smoking cessation at the study endpoint ( week 12 ) . At the 6-month follow-up , 40 % of the patients ( 4 of 10 ) who received bupropion SR maintained smoking cessation . One ( 20 % ) of the five patients who received placebo stopped smoking and maintained smoking cessation at the 6-month follow-up . Bupropion SR was generally well-tolerated in combination with other psychotropic medications . Bupropion SR may be effective in helping patients who desire to quit smoking and who also have a concomitant anxiety disorder , such as PTSD BACKGROUND The use of bupropion , a smoking cessation aid , has been associated with improved health-related quality of life ( HRQOL ) in the general population of smokers ; but , its effect on HRQOL in post-myocardial infa rct ion ( MI ) patients remains unknown . OBJECTIVES To examine the effect of bupropion on HRQOL in post-MI patients who are attempting to quit smoking . METHODS To accomplish this objective , we used data from a r and omized , double-blind , placebo-controlled trial in 392 hospitalized post-MI patients . Treatment duration was 9 weeks , and follow-up was 12 months . HRQOL was assessed via the EuroQol-5D ( EQ-5D ) question naire , which includes 5 dimensions ( mobility , self-care , daily activities , pain/discomfort , and anxiety/depression ) . Analyses were restricted to patients ( n=225 ) who completed the EQ-5D at baseline , 6 months , and 12 months . RESULTS Patients r and omized to bupropion ( n=109 ) and those r and omized to placebo ( n=116 ) experienced similar improvements in HRQOL during follow-up ( difference in change in EQ-5D index from baseline to 6 months = 0.02 , 95 % confidence interval [ CI ] = -0.04 , 0.08 ; from baseline to 12 months = 0.02 , 95 % CI = -0.04 , 0.08 ) . No between-group differences were observed in any of the 5 dimensions . Similar improvements in HRQOL were observed between patients who remained abstinent and those who relapsed . Lower baseline HRQOL , defined as having a HRQOL that was less than the median value , was associated with decreased smoking abstinence at 12 months follow-up ( odds ratio OR = 0.39 , 95 % CI = 0.22 , 0.68 ) . CONCLUSIONS Bupropion does not improve HRQOL among patients attempting to quit smoking post-MI OBJECTIVES We evaluated smoking-cessation efficacy of an extended course of sustained-release bupropion ( bupropion SR ) and cognitive-behavioral treatment ( CBT ) . METHODS Participants who smoked at least 10 cigarettes per day and who smoked within 30 minutes of arising ( n = 406 ) completed a 12-week smoking-cessation treatment including group counseling , nicotine-replacement therapy , and bupropion SR . Participants were then r and omly assigned to 1 of 5 conditions : ( 1 ) no further treatment , ( 2 ) active bupropion SR for 40 weeks , ( 3 ) placebo for 40 weeks , ( 4 ) active bupropion SR and 11 sessions of CBT for 40 weeks ( A-CBT ) , or ( 5 ) placebo and 11 sessions of CBT for 40 weeks . Participants were assessed at baseline and at weeks 12 , 24 , 52 , 64 , and 104 . RESULTS A-CBT was not superior to the other 3 extended treatments . From weeks 12 through 104 , all extended treatment conditions were superior to st and ard treatment . At weeks 64 and 104 , the 2 CBT conditions produced significantly higher abstinence rates than did the other 3 conditions . CONCLUSIONS Brief contact with providers can increase abstinence during treatment . CBT may increase long-term abstinence after extended treatment is terminated OBJECTIVE The purpose of this study was to evaluate the efficacy of long-term use of bupropion sustained release ( SR ) , the nicotine patch , and the combination of these 2 treatments in patients who initially failed treatment . METHODS This was a post hoc analysis of a multicenter , double-blind , r and omized , placebo-controlled clinical trial in 893 smokers . Patients were r and omly assigned to 9 weeks of treatment with placebo ( n = 160 ) , bupropion SR ( n = 244 ) , nicotine patch ( n = 244 ) , or a combination of nicotine patch and bupropion SR ( n = 245 ) . The study was originally design ed with a follow-up period of 52 weeks . In this analysis , short-term success was defined as smoking cessation after 14 or 21 days of therapy and long-term success was defined as smoking cessation after > 21 days of therapy . Patients who did not achieve short-term success were evaluated for long-term success at week 9 ( end of treatment ) , 6 months , and 1 year after the start of the study . RESULTS The mean age of the smokers was 44 years . The majority ( 93 % ) of patients were white , and 52 % were female . The study subjects smoked an average of 27 cigarettes per day . Among the 467 patients who initially failed treatment in the first 3 weeks , treatment with bupropion SR alone and in combination with the nicotine patch produced significant increases in successful smoking cessation rates from weeks 4 to 9 ( 19 % bupropion SR or combination , 7 % nicotine patch , 7 % placebo ) , at month 6 ( 11 % bupropion SR , 13 % combination , 2 % nicotine patch , 3 % placebo ) , and at month 12 ( 10 % bupropion SR , 7 % combination , 2 % nicotine patch , 1 % placebo ) ( P < 0.05 for bupropion SR and combination vs nicotine patch or placebo ) . CONCLUSION Among patients who initially failed treatment , continued therapy with bupropion SR , either alone or in combination with the nicotine patch , result ed in significantly higher short- and long-term smoking cessation rates than treatment with the nicotine patch alone or placebo Many effective behavioral and pharmacologic therapies are now available for treatment of smoking . The most effective strategy for treatment is combined behavioral intervention and pharmacologic therapy ( 1 ) . Effective pharmacologic interventions for smoking cessation include several types of nicotine replacement and use of the non-nicotine medication bupropion ( 2 , 3 ) . Despite treatment advances , smoking relapse after successful intervention for smoking cessation occurs in 70 % to 80 % of patients within 6 to 12 months ( 4 ) . Studies of relapse prevention strategies suggest that teaching coping skills may reduce the risk for relapse , but other behavioral therapies have shown little benefit ( 5 , 6 ) . Because pharmacologic therapy for smoking cessation has been proven effective and behavioral relapse prevention strategies alone have shown no great benefit , pharmacologic therapy for relapse prevention should be evaluated . Bupropion has been proven an effective intervention for smoking cessation , both as a single therapy and in combination with nicotine-patch therapy ( 2 , 3 ) . Because bupropion is effective for initiating abstinence from smoking and is safe for long-term therapy , we hypothesized that prolonged bupropion treatment in recently abstinent smokers would decrease the relapse rate . We compared sustained-release bupropion treatment with placebo for 1 year in participants who achieved initial abstinence after 7 weeks of therapy with open-label , sustained-release bupropion . Methods Participants This r and omized , double-blind , placebo-controlled study of relapse prevention was performed at five sites ( Mayo Clinic , Rochester , Minnesota ; the Palo Alto Center for Pulmonary Disease Prevention , Palo Alto , California ; Brown University , Providence , Rhode Isl and ; Oregon Health Sciences University , Portl and , Oregon ; and Massachusetts General Hospital , Boston , Massachusetts ) and was approved by the institutional review board at each site . We recruited participants through advertisements and press releases . After passing an initial screening interview by telephone , participants attended an informational meeting . At this meeting , the study was explained and the participants completed question naires and gave written , informed consent . The volunteers were eligible for study inclusion if they were 18 years of age or older , had smoked an average of at least 15 cigarettes or more per day for the past year , were motivated to stop smoking , and were in generally good health . Only one smoker per household was allowed in the study . Exclusion criteria included a personal or family history of a seizure disorder ; history of severe head trauma ; predisposition to seizures ( such as history of brain tumor or stroke ) ; history or current diagnosis of anorexia nervosa or bulimia ; presence of an unstable medical or psychiatric condition ; pregnancy ; lactation ; dependence on alcohol or other nonnicotine substance in the past year ; current use of psychotropic medications ; previous use of bupropion ; current use of tobacco products other than cigarettes ; or current use of any therapy for smoking cessation [ such as nicotine replacement therapy ; fluoxetine , clonidine , buspirone , or doxepin therapy ; or behavioral therapy ] . Persons with current major depression were also excluded . Potential participants were deemed to have current major depression if : 1 ) they met the criteria for this condition on the basis of their responses in a structured clinical interview [ conducted by a trained study assistant ] , or 2 ) they were judged to have major depression by the physician performing the entrance history and physical examination ( 7 ) . Treatment Beginning at the baseline visit and continuing through study week 7 , all participants received open-label , sustained-release bupropion ( bupropion SR ) , 300 mg/d ( 150 mg/d for 3 days , followed by 150 mg twice daily ) . At the baseline visit , participants were instructed to set a target quitting date after 1 week of medication use [ usually day 8 of therapy ] . Each participant attended weekly follow-up visits during the 7-week open-label phase . Participants were eligible for r and om assignment to receive bupropion or placebo in the double-blind phase if they 1 ) reported not smoking [ not even a puff ] during week 7 of the open-label phase and 2 ) had their self-report confirmed by an expired carbon monoxide level of 10 parts per million ( ppm ) or less . The r and omly assigned participants returned for 14 visits during the double-blind phase ( at weeks 8 , 9 , 10 , 12 , 16 , 20 , 24 , 28 , 32 , 36 , 40 , 44 , 48 , and 52 ) and 5 visits during the follow-up year ( at weeks 53 , 56 , 64 , 78 , and 104 ) . Participants also received a telephone follow-up at 21 months after study enrollment . At the baseline physical examination , each participant received a brief personalized message from the examining physician to stop smoking , set a target quitting date , and received self-help material that was based on a smoking cessation program design ed by the U.S. National Cancer Institute ( 8) . At each visit during the open-label and double-blind study phases , study assistants counseled participants for approximately 10 to 15 minutes . R and omization to the placebo or bupropion groups was computer generated at a central location ; the investigators did not know the patient assignments . All bupropion and placebo pills were identical in shape , size , and color . Assessment s At baseline , participants had a physical examination ; underwent chest radiography , laboratory testing , and electrocardiography ; and completed a Fagerstrm Tolerance Question naire and a Beck Depression Inventory . The Fagerstrm Tolerance Question naire is a widely used measure of nicotine dependence with scores that range from 0 to 11 ; scores of 6 or greater indicate higher levels of dependence ( 9 , 10 ) . At each visit through week 53 , study assistants recorded adverse experiences , as well as use of study and concomitant medications . Participants maintained a daily diary of withdrawal symptoms ( 11 ) and daily cigarette use that was review ed at each visit through week 12 . The Beck Depression Inventory ( administered at baseline and weeks 7 , 8 , 12 , 52 , 53 , 56 , 78 , and 104 ) is a 21-item , self-administered question naire that assesses severity of depressive symptoms ( 12 ) . Smoking status was self-reported at each visit ; reports of abstinence were considered vali date d with a measurement of carbon monoxide level in expired air of no higher than 10 ppm . Outcome Measures The main outcomes of interest were 1 ) weekly point-prevalence abstinence during medication treatment , 2 ) continuous abstinence during medication treatment , and 3 ) time to first relapse . Secondary outcomes included weight change over time and point prevalence and continuous-abstinence rates after completion of drug therapy . The weekly point-prevalence smoking status was defined as 1 ) self-report of not smoking during the previous 7 days that was confirmed by an expired air carbon monoxide level of 10 ppm or lower and 2 ) two or fewer consecutive missed visits . Smoking relapse was defined as a self report of smoking or an expired air carbon monoxide level greater than 10 ppm . Participants were also considered to have smoking relapse if they missed more than two consecutive visits . All participants meeting the abstinence criteria at every visit were considered continuously abstinent . Self-report determined the date of smoking relapse . For participants who self-reported not smoking but who were classified as smoking because of an elevated carbon monoxide level or because of consecutive missed visits , the date of relapse was defined as the day after the most recent previous study visit at which smoking abstinence was biochemically confirmed . Statistical Analysis We determined that we needed a sample size of 170 participants in each r and omly assigned treatment group to detect a significant between-group difference in end-of-treatment abstinence rates of 0.15 at a significance level of 0.05 and a power of 0.80 . Assuming an abstinence rate of 35 % for week 7 of the open-label phase , we determined that up to 1000 enrollees were needed to ensure a minimum sample of 340 nonsmoking participants ( 170 per group ) for r and omization . The 1-week point prevalence for smoking status during week 7 of the open-label bupropion phase was used to determine eligibility for r and om assignment to receive placebo or active sustained-release bupropion , 300 mg/d . To compare the baseline characteristics of the bupropion and placebo recipients , we used the two- sample t-test and the chi-square test for analysis of continuous and categorical variables , respectively . The efficacy of bupropion for preventing smoking relapse during the double-blind medication phase and follow-up phase was assessed by analyzing time to first smoking relapse . We used KaplanMeier survival estimates and a proportional hazards regression model ( 13 , 14 ) to analyze time to first smoking relapse . For this analysis , time to first relapse was defined as the date of first relapse minus the date of r and omization . For participants without relapse , time to first relapse was censored by using the date of their final ( week 104 ) study visit . For the proportional hazards regression analysis , the response variable was time to first smoking relapse , and the independent variable was treatment . R and omization was stratified according to study site to ensure that similar numbers of participants were assigned to the treatment groups at each site . We verified that the treatment effect was not dependent on study site by performing an initial analysis that included the interaction of treatment by study site . Subsequently , we used a proportional hazards regression analysis with study site as a stratification factor to assess differences between treatment groups . Rates of point prevalence and continuous smoking abstinence were compared between treatment groups by using a logistic regression analysis with smoking status as the dependent variable and BACKGROUND Previous research has shown that smokers have reduced brain and platelet monoamine oxidase B ( MAOB ) activity . This is probably due to some components of tobacco smoke . When smokers quit , MAOB activity returns to normal . Reduced MAO activity may increase nicotine 's addictive potential . AIMS To assess whether lazabemide , a reversible selective MAOB inhibitor , promotes smoking cessation . STUDY DESIGN Double-blind , r and omized , placebo-controlled , multicenter phase II study . Placebo , lazabemide 100 mg/day and 200 mg/day were administered for 8 weeks . This was a dose finding , proof-of-concept , exploratory study . SETTING General practice s and anti-smoking clinics in France and Belgium . PARTICIPANTS Smokers smoking > or=15 cigarettes per day and motivated to quit . MAIN OUTCOME MEASURE Sustained abstinence during the last 4 weeks of the study . FINDINGS The study was discontinued prematurely by the sponsor before r and omization of the planned 420 smokers because of liver toxicity observed in other indications . Data of 330 r and omized subjects could be analysed . Sustained abstinence during the last 4 weeks of treatment was 9 % , 11 % and 17 % in the intent-to-treat population [ P for trend : 0.036 ( one-sided ) ] ; 11 % , 14 % and 21 % in the intent-to-treat population of smokers without those excluded because of discontinuation of the study [ n = 262 , P for trend : 0.02 ( one-sided ) ] , and 19 % , 27 % and 35 % in completers [ P for trend : 0.03 ( one-sided ) ] , in the placebo , lazabemide 100 mg/day and lazabemide 200 mg/day groups , respectively . Point prevalence abstinence ( intent-to-treat population ) at the end of treatment ( week 8) was 17 % , 19 % and 30 % in the placebo , lazabemide 100 mg/day and lazabemide 200 mg/day groups , respectively ( placebo vs. lazabemide 200 mg/day : P = 0.01 , one-sided ) . No treatment emergent major adverse event occurred . More nausea and insomnia were reported with lazabemide than with placebo . CONCLUSIONS MAOB inhibitors are promising treatments as an aid in smoking cessation . There may be an interest to develop MAOB inhibitors with an acceptable toxicity profile . Further studies may associate MAOB inhibitors with nicotine replacement therapies to increase therapeutic efficacy Among smokers , women may be at greater risk than men for developing smoking-related diseases , perhaps because they have greater difficulty quitting smoking , as suggested by numerous studies . In the present study , we hypothesized that bupropion would reduce this gender disparity among 314 women and 241 men enrolled in a placebo-controlled , r and omized trial using behavioral counseling plus 10 weeks of bupropion ( 300 mg ) . Prolonged abstinence and biochemically verified point prevalence outcomes were measured at end of treatment ( 8 weeks after the quit date ) and at 6-month follow-up . A logistic regression model of 6-month prolonged abstinence and a Cox regression ( survival analysis ) model revealed a significant gender by smoking rate by drug interaction and a main effect for marital status . This three-way interaction suggests that bupropion particularly benefited men who smoked more than one pack of cigarettes per day at baseline and , conversely , women who smoked a pack or less . The point prevalence logistic regression model showed no evidence that either gender or smoking rate modified the effect of treatment . These results suggest that bupropion treatment may reduce the gender disparity in prolonged abstinence rates among lighter smokers Weight gain typically accompanies smoking cessation , and women smokers concerned about postcessation weight gain are prone to substantial gain . Little is known about the ways in which cessation affects dietary composition . Underst and ing postcessation changes in dietary composition may inform the design of smoking cessation interventions to address postcessation weight gain . Participants were women smokers concerned about postcessation weight gain enrolled in a r and omized trial and assigned to either bupropion or placebo and to either st and ard cessation intervention or st and ard intervention plus components to address weight concerns . Women completed three , 24-hr food recall interviews at baseline , and at 1 and 6 months following a targeted quit date . At 6 months , 22 % of women were abstinent and had gained 3.6 ( ±2.7 ) kg , compared to 0.91 ( ±2.0 ) kg for women who continued to smoke , p = .42 . Abstinent women reported significantly higher energy intake and consumed a smaller percentage of fat across assessment points than did those who continued to smoke . Intervention was not associated with differential weight gain or change in percent of calories from protein , fat , or carbohydrates . This study is the first documentation of energy and macronutrient intake during smoking cessation treatment using a vali date d 24-hr dietary recall methodology . Although cessation was associated with overall increases in energy intake among women , neither bupropion nor weight concerns treatment affected energy or macronutrient intake . Future research to underst and the relation between cessation and dietary intake needs to replicate and extend these findings to eluci date how , if at all , smoking cessation affects dietary intake BACKGROUND the effects of smoking and smoking cessation on lipoproteins have not been studied in a large contemporary group of smokers . This study was design ed to determine the effects of smoking cessation on lipoproteins . METHODS this was a 1-year , prospect i ve , double-blind , r and omized , placebo-controlled clinical trial of the effects of 5 smoking cessation pharmacotherapies . Fasting nuclear magnetic resonance spectroscopy lipoprotein profiles were obtained before and 1 year after the target smoking cessation date . The effects of smoking cessation and predictors of changes in lipoproteins after 1 year were identified by multivariable regression . RESULTS the 1,504 current smokers were ( mean [ SD ] ) 45.4 ( 11.3 ) years old and smoked 21.4 ( 8.9 ) cigarettes per day at baseline . Of the 923 adult smokers who returned at 1 year , 334 ( 36.2 % ) had quit smoking . Despite gaining more weight ( 4.6 kg [ 5.7 ] vs 0.7 kg [ 5.1 ] , P < .001 ] , abstainers had increases in high-density lipoprotein cholesterol ( HDL-C ) ( 2.4 [ 8.3 ] vs 0.1 [ 8.8 ] mg/dL , P < .001 ) , total HDL ( 1.0 [ 4.6 ] vs -0.3 micromol/L [ 5.0 ] , P < .001 ) , and large HDL ( 0.6 [ 2.2 ] vs 0.1 [ 2.1 ] micromol/L , P = .003 ) particles compared with continuing smokers . Significant changes in low-density lipoprotein ( LDL ) cholesterol and particles were not observed . After adjustment , abstinence from smoking ( P < .001 ) was independently associated with increases in HDL-C and total HDL particles . These effects were stronger in women . CONCLUSIONS despite weight gain , smoking cessation improved HDL-C , total HDL , and large HDL particles , especially in women . Smoking cessation did not affect LDL or LDL size . Increases in HDL may mediate part of the reduced cardiovascular disease risk observed after smoking cessation The relationship between major depressive disorder ( MDD ) , treatment modality , and mood was evaluated in smokers participating in cessation programs . Participants ( N = 549 , 53.7 % women , 46.3 % men , 28 % endorsing past MDD episodes ) were r and omly assigned to a cognitive-behavioral treatment ( CBT ) or health education ( HE ) intervention . Participants with a history of recurrent MDD ( MDD-R ) had higher rates of abstinence in CBT compared with HE even when the contribution of mood and the interaction between mood and an MDD x Treatment variable were included in the model . Likewise , higher levels of mood disturbance were reported by MDD-R smokers compared with those reporting a single episode . The study replicated results reported by R. A. Brown et al. ( 2001 ) and exp and ed upon them by evaluating the differential contribution of poor mood on cessation outcomes relative to MDD history Despite the efficacy of bupropion for smoking cessation , smokers exhibit variability in treatment outcome . The CYP2B6 gene has been implicated in bupropion kinetics and nicotine metabolism , and is a plausible c and i date for pharmacogenetic studies of treatment response . We investigated whether a functional genetic polymorphism in the CYP2B6 gene predicts smoking outcomes in a placebo-controlled r and omized trial . Four hundred and twenty-six smokers of European Caucasian ancestry provided blood sample s and received bupropion ( 300 mg/day for 10 weeks ) or placebo , plus counseling . Smoking status , abstinence symptoms and side-effects were recorded weekly , and smoking status was verified at the end of treatment and at 6-month follow-up . Smokers with a decreased activity variant of CYP2B6 reported greater increases in cravings for cigarettes following the target quit date and had higher relapse rates . These effects were modified by a significant gender x genotype x treatment interaction , suggesting that bupropion attenuated the effects of genotype among female smokers . We conclude that smokers with the CYP2B6 variant may be more vulnerable to abstinence symptoms and relapse . Bupropion may attenuate these effects , especially among females . Additional trials are warranted to confirm these results , as are studies to explore the neurobiological mechanisms . Such research could ultimately enable practitioners to select the optimal type and dose of medication for individual smokers Adult smokers ( N = 253 ) without clinical ly significant depression were r and omized on a double-blind basis to receive fluoxetine ( 30 or 60 mg daily ) or a placebo for 10 weeks in combination with cognitive-behavioral therapy ( CBT ) . It was predicted that fluoxetine would selectively benefit smokers with higher baseline depression , nicotine dependence , and weight concern and lower self-efficacy about quitting smoking . Among those who completed the prescribed treatment regimen , baseline depression scores moderated the treatment response . Logistic regression analyses showed that 1 and 3 months after the quit date , fluoxetine increased the likelihood of abstinence , as compared with placebo , among smokers with minor depression but not among those with little or no depression . Results suggests that , as an adjunct to CBT , fluoxetine enhances cessation by selectively benefiting medication-compliant smokers who display even sub clinical levels of depression AIMS Smoking cessation treatment trials often require that smokers quit on or before a protocol -defined date . The goals of this paper were to : ( 1 ) identify factors associated with adherence to a protocol -defined quit date and ( 2 ) determine whether such adherence predicts cessation outcome ( relapse ) . DESIGN A quasi-experimental secondary analysis of data collected from a r and omized placebo-controlled trial of fluoxetine ( 60 mg or 30 mg ) versus placebo for smoking cessation . SETTING AND PARTICIPANTS Clinic-based smoking cessation treatment program comprising 989 non-depressed smokers . INTERVENTION Participants received cognitive behavioral therapy for smoking cessation and either study medication or placebo for 10 weeks . They were required to set a quit date within 2 weeks of their second study visit ( by visit 4 ) . FINDINGS Significant predictors of quit date adherence were low nicotine dependence and active drug treatment . High-dose fluoxetine ( 60 mg ) and male gender were protective against relapse . Adherence to quit date was not an independent predictor of relapse ; instead there was a significant interaction between quit date adherence and gender . Among non-adherers to the quit date , women were more than 2.5 times as likely as men to relapse ; among adherers to the quit date , women were only 1.3 times as likely as men to relapse . CONCLUSIONS Although women were more likely than men to relapse regardless of quit date adherence , adherence was strongly protective against relapse for women OBJECTIVES To identify predictors of smoking abstinence at the end of medication use that could assist in the optimal use of a sustained-release ( SR ) form of bupropion for treating cigarette smokers . DESIGN A double-blind , placebo-controlled , dose-response trial . SETTING Multicenter ( three sites ) study conducted in the United States . PARTICIPANTS Six hundred fifteen healthy men and women ( > or = 18 years of age ) who were smoking > or = 15 cigarettes per day and who were motivated to stop smoking . INTERVENTION R and om assignment of patients to placebo or SR bupropion treatment , 100 , 150 , or 300 mg/d , for 7 weeks ( total duration of study was 52 weeks : 7 weeks of treatment and 45 weeks of follow-up ) . MEASUREMENTS AND RESULTS Logistic regression was used to identify predictors of abstinence at the end of the medication phase . Univariate predictors included the following : bupropion dose ( p < 0.001 ) ; older age ( p = 0.024 ) ; lower number of cigarettes smoked per day ( cpd ) ( p < 0.001 ) ; lower Fagerström Tolerance Question naire score ( p = 0.011 ) ; longest time previously abstinent that was < 24 h or > 4 weeks ( p < 0.001 ) ; absence of other smokers in the household ( p = 0.021 ) ; greater number of previous stop attempts ( p = 0.019 ) ; and study site ( p = 0.004 ) . Multivariate predictors of abstinence at the end of the medication phase were the following : higher bupropion dose ( p < 0.001 ) ; lower number of cpd ( p < 0.001 ) ; longest time previously abstinent from smoking ( p = 0.002 ) ; male gender ( p = 0.014 ) ; and study site ( p = 0.021 ) . CONCLUSION Bupropion SR therapy was effective in treating cigarette smokers independently of all other characteristics studied . Lower smoking rate , brief periods ( ie , < 24 h ) or long periods ( ie , > 4 weeks ) of abstinence with previous attempts to stop smoking , and male gender were predictive of better outcomes , independent of the dose of bupropion that was used Bupropion is indicated to promote smoking cessation . Animal studies suggest that the pharmacologic activity of bupropion can be mediated by its major metabolite , hydroxybupropion . We measured plasma bupropion and its metabolite levels in a double‐blind , placebo controlled , r and omized smoking‐cessation trial . Among the treatment‐adherent individuals , higher hydroxybupropion concentrations ( per μg/ml ) result ed in better smoking‐cessation outcomes ( week 3 , 7 , and 26 odds ratio ( OR ) = 2.82 , 2.96 , and 2.37 , respectively , P = 0.005–0.040 ) ; this was not observed with bupropion levels ( OR = 1.00–1.03 , P = 0.59–0.90 ) . Genetic variation in CYP2B6 , the enzyme that metabolizes bupropion to hydroxybupropion , was identified as a significant source of variability in hydroxybupropion formation . Our data indicate that hydroxybupropion contributes to the pharmacologic effects of bupropion for smoking cessation , and that variability in response to bupropion treatment is related to variability in CYP2B6‐mediated hydroxybupropion formation . These findings suggest that dosing of bupropion to achieve a hydroxybupropion level of 0.7 μg/ml or increasing bupropion dose for CYP2B6 slow metabolizers could improve bupropion 's cessation outcomes Background : Knowledge pertaining to the effectiveness of smoking cessation treatments and patient characteristics that may affect success may enable smokers and clinicians to select individualized treatment for each patient and ultimately increase the success rate of smoking cessation in general . Objective : To evaluate the effectiveness of bupropion as a smoking cessation agent when used in routine clinical practice . Methods : This was a prospect i ve , observational study with a one year follow-up period . Adult smokers presenting to community pharmacies in British Columbia , Canada , with an index prescription for bupropion for smoking cessation ( N = 205 ) were eligible . The primary outcome was the biochemically vali date d 12 month point abstinence ( PA ) rate from smoking . Secondary outcomes included the frequency of adverse events , patterns of bupropion use in routine clinical practice , and possible predictors of bupropion effectiveness . Results : The vali date d 12 month PA rate was 21.0 % . Of subjects who reported taking at least one dose of bupropion , 70.4 % ( 126/179 ) experienced at least one adverse event and 29.6 % ( 53/179 ) reported stopping the drug due to adverse effects . Greater length of time on bupropion ( OR 0.98 ) and a lower cigarette pack-year history ( OR 1.05 ) were associated with an increase in the odds of smoking cessation . Conclusions : Subjects receiving bupropion in a real-life setting exhibited a similar abstinence rate at 12 months as has been observed in the active drug groups of placebo-controlled clinical trials . However , the patterns of use and discontinuation rate due to adverse events differed substantially from those observed in early efficacy studies Some studies have shown that female smokers and smokers with a history of depression have an increased risk of relapse following smoking cessation treatment . This study examined the efficacy of bupropion sustained-release ( SR ) and the nicotine patch for smoking cessation in subgroups of smokers at possible risk for relapse . Data for this study were from a previously published r and omized , double-blind , placebo-controlled clinical trial in which 893 smokers were r and omized to four treatment conditions : placebo tablet + placebo patch , placebo tablet + 21 mg/24-hr nicotine patch , 300 mg bupropion SR + placebo patch , and 300 mg bupropion SR + 21 mg/24-hr nicotine patch . Study medication continued for 8 weeks after the quit day ; brief individual cessation counseling was provided during weekly clinic visits . In comparison to the placebo tablet , bupropion SR approximately tripled 1-year non-smoking rates among women and previously depressed individuals . In contrast , the nicotine patch did not significantly improve cessation rates for any group . We conclude that bupropion SR is a first-line treatment for smoking that has the potential to benefit all smokers , especially women and the previously depressed There is an association between smoking and depression , yet the herbal antidepressant St John 's wort ( Hypericum perforatum L. ; SJW ) herb extract has not previously been investigated as an aid in smoking cessation . In this open , uncontrolled , pilot study , 28 smokers of 10 or more cigarettes per day for at least one year were r and omised to receive SJW herb extract ( LI-160 ) 300 mg once or twice daily taken for one week before and continued for 3 months after a target quit date . In addition , all participants received motivational/behavioural support from a trained pharmacist . At 3 months , the point prevalence and continuous abstinence rates were both 18 % , and at 12 months were 0 % . Fifteen participants ( 54 % ) reported 23 adverse events up to the end of the 3-month follow-up period . There was no statistically significant difference in the frequency of adverse events for participants taking SJW once or twice daily ( p > 0.05 ) . Most adverse events were mild , transient and non-serious . This preliminary study has not provided convincing evidence that a SJW herb extract plus individual motivational/behavioural support is likely to be effective as an aid in smoking cessation . However , it may be premature to rule out a possible effect on the basis of a single , uncontrolled pilot study , and other approaches involving SJW extract may warrant investigation OBJECTIVE A prospect i ve r and omized study was undertaken to assess the effectiveness and side effect profiles of nicotine patch and bupropion therapies for smoking cessation . METHODS Three hundred and fifty patients were referred to our smoking cessation program in the Department of Pulmonary Diseases , Gaziantep University between September 2002 and July 2003 . Of these , only 131 patients fulfilled the trial criteria . We r and omized the patients into nicotine patch ( n=50 ) , bupropion ( n=50 ) and control groups ( n=31 ) . Cases were followed up for 24 weeks . Question naires including the Fagerstrom test for nicotine dependence and Beck Depression Inventory were carried out at initial evaluation . Declaration of quitting and exhaled carbon monoxide level less than 10 ppm was accepted as success criteria . RESULTS Success rates were 26 % for nicotine patch group , 26 % for bupropion and 16 % for control group at the end of the 24th week ( p=0.56 ) . Beck depression inventory scores did not differ significantly between the groups , however none of the cases with scores greater than 13 succeeded regardless of the group . Mean body weight at baseline and change at 6 months did not differ significantly between the groups . Sleep disturbance was significantly more common in nicotine patch and bupropion groups than the control group ( p=0.008 ) . CONCLUSION The present study reinforces the role of medical doctors and importance of close follow up in smoking cessation , and directed counseling is quite as effective as pharmacologic therapy and is the sole approach without any adverse effects Given high rates of smoking among cancer patients , smoking cessation treatment is crucial ; yet limited data exist to guide integration of such trials into the oncologic context . In order to determine the feasibility of conducting smoking cessation clinical trials with cancer patients , screening and baseline data from a large r and omized placebo-controlled pharmacotherapy trial were analyzed . Descriptive statistics and regression analyses were used to compare enrollees to decliners , describe program enrollees , and assess correlates of confidence in quitting smoking . Out of 14,514 screened patients , 263 ( < 2 % ) were eligible ; 43 ( 16 % ) refused enrollment . Among the eligible patients , 220 ( 84 % ) enrolled . Enrollment barriers included smoking rate , medical history/contraindicated medication , lack of interest , and language . Compared to enrollees , decliners were more likely to have advanced cancer . The trial enrolled a sample of 67 ( > 30 % ) African Americans ; participants had extensive smoking histories ; many were highly nicotine dependent ; and participants consumed about seven alcoholic beverages/week on average . Head and neck and breast cancer were the most common tumors . About 52 ( 25 % ) reported depressive symptoms . A higher level of confidence to quit smoking was related to lower depression and lower tumor stage . Integrating a smoking cessation clinical trial into the oncologic setting is challenging , yet feasible . Recruitment strategies are needed for patients with advanced disease and specific cancers . Once enrolled , addressing participant ’s depressive symptoms is critical for promoting cessation INTRODUCTION Bupropion is a first-line pharmacological aid for smoking cessation ; however , no clinical trials have been conducted in a general population of hospitalized smokers . METHODS We enrolled 85 smokers in a hospital-based r and omized smoking cessation trial conducted at the San Francisco Veterans Affairs Medical Center . A total of 42 participants received a 7-week course of sustained-release bupropion and 43 participants received placebo . All participants received cognitive-behavioral counseling . We screened 14,997 patients , of whom 25 % were current smokers . Of the 536 smokers who met the entry criteria , 451 opted not to enroll . We determined on-medication , end-of-medication , 3-month , and 6-month smoking cessation rates . RESULTS At the end of 7 weeks of drug treatment , self-reported quit rates were equivalent in the bupropion and placebo arms , 37 % versus 33 % , respectively ( p = .82 ) . The vali date d quit rates for the bupropion and placebo groups were 27 % versus 29 % , respectively ( p = 1.00 ) . At 6 months , the self-reported quit rates were 29 % in the bupropion group and 41 % in the placebo group ( p = .36 ) . In a comparison of 6-month quit rates , vali date d either by salivary cotinine or by spousal proxy , we found nonsignificantly higher quit rates in the placebo group than in the bupropion group , 31 % versus 15 % ( p = .12 ) . DISCUSSION The addition of sustained-release bupropion to counseling did not increase quit rates , but the study was underpowered . Because of the secular trend toward shorter hospital stays , recruitment was very difficult , raising questions regarding the feasibility of future hospital-based smoking cessation trials and interventions OBJECTIVE The authors assessed the efficacy and safety of combination treatment with varenicline and sustained-release bupropion for smokers who , based on an assessment of initial smoking reduction prior to the quit date , were deemed unlikely to achieve abstinence using nicotine patch treatment . METHOD In a r and omized , double-blind , parallel-group adaptive treatment trial , the authors identified 222 cigarette smokers who failed to show a reduction of more than 50 % in smoking after 1 week of nicotine patch treatment . Smokers were r and omly assigned to receive 12 weeks of varenicline plus bupropion or varenicline plus placebo . The primary outcome measure was continuous smoking abstinence at weeks 8 - 11 after the target quit date . RESULTS Both treatments were well tolerated . Participants who received the combination treatment had a significantly higher abstinence rate than those who received varenicline plus placebo ( 39.8 % compared with 25.9 % ; odds ratio=1.89 ; 95 % CI=1.07 , 3.35 ) . Combination treatment had a significantly greater effect on abstinence rate in male smokers ( odds ratio=4.26 ; 95 % CI=1.73 , 10.49 ) than in female smokers ( odds ratio=0.94 ; 95 % CI=0.43 , 2.05 ) . It also had a significantly greater effect in highly nicotine-dependent smokers ( odds ratio=3.51 , 95 % CI=1.64 , 7.51 ) than in smokers with lower levels of dependence ( odds ratio=0.71 , 95 % CI=0.28 , 1.80 ) . CONCLUSIONS Among smokers who did not show a sufficient initial response to prequit nicotine patch treatment , combination treatment with varenicline and bupropion proved more efficacious than varenicline alone for male smokers and for smokers with a high degree of nicotine dependence Objective To compare the risk of suicide , self harm , and depression in patients prescribed varenicline or bupropion with those prescribed nicotine replacement therapy . Design Prospect i ve cohort study within the Clinical Practice Research Data link . Setting 349 general practice s in Engl and . Participants 119 546 men and women aged 18 years and over who used a smoking cessation product between 1 September 2006 and 31 October 2011 . There were 81 545 users of nicotine replacement products ( 68.2 % of all users of smoking cessation medicines ) , 6741 bupropion ( 5.6 % ) , and 31 260 varenicline ( 26.2 % ) users . Main outcome measures Outcomes were treated depression and fatal and non-fatal self harm within three months of the first smoking cessation prescription , determined from linkage with mortality data from the Office for National Statistics ( for suicide ) and Hospital Episode Statistics data ( for hospital admissions relating to non-fatal self harm ) . Hazard ratios or risk differences were estimated using Cox multivariable regression models , propensity score matching , and instrumental variable analysis using physicians ’ prescribing preferences as an instrument . Sensitivity analyses were performed for outcomes at six and nine months . Results We detected 92 cases of fatal and non-fatal self harm ( 326.5 events per 100 000 person years ) and 1094 primary care records of treated depression ( 6963.3 per 100 000 person years ) . Cox regression analyses showed no evidence that patients prescribed varenicline had higher risks of fatal or non-fatal self harm ( hazard ratio 0.88 , 95 % confidence interval 0.52 to 1.49 ) or treated depression ( 0.75 , 0.65 to 0.87 ) compared with those prescribed nicotine replacement therapy . There was no evidence that patients prescribed bupropion had a higher risk of fatal or non-fatal self harm ( 0.83 , 0.30 to 2.31 ) or of treated depression ( 0.63 , 0.46 to 0.87 ) compared with patients prescribed nicotine replacement therapy . Similar findings were obtained using propensity score methods and instrumental variable analyses . Conclusions There is no evidence of an increased risk of suicidal behaviour in patients prescribed varenicline or bupropion compared with those prescribed nicotine replacement therapy . These findings should be reassuring for users and prescribers of smoking cessation medicines INTRODUCTION Social support has been linked to quitting smoking , but the mechanisms by which social support affects cessation are poorly understood . The current study tested a stress-buffering model of social support , which posits that social support protects or " buffers " individuals from stress related to quitting smoking . We hypothesized that social support would be negatively associated with risk of relapse , and that this effect would be mediated by reduced withdrawal and depressive symptoms ( i.e. , cessation-related stress ) over time . Further , we predicted that trait neuroticism would moderate this mediational effect , such that individuals high in negative affectivity would show the greatest stress-buffering effects of social support . METHODS Participants were weight-concerned women ( n = 349 ) ages 18 - 65 enrolled in a r and omized , double-blind , placebo-controlled smoking cessation trial of bupropion and cognitive behavioral therapy . Social support was assessed at baseline , and biochemically-verified abstinence , withdrawal-related symptoms , and depressive symptoms were assessed at 1- , 3- , 6- , and 12-months follow-up . RESULTS Social support was negatively related to risk of relapse in survival models and negatively related to withdrawal symptoms and depression in mixed effects models . These relationships held after controlling for the effects of pre-quit day negative affect and depression symptoms , assignment to treatment condition , and number of cigarettes smoked per day . A temporal mediation model showed that the effect of social support on risk of relapse was mediated by reductions in withdrawal symptoms over time but not by depression over time . Contrary to hypotheses , we did not find that neuroticism moderated this mediation effect . CONCLUSIONS Increased social support may buffer women from the harmful effects of cessation-related withdrawal symptoms , which in turn improve cessation outcomes OBJECTIVE The objective of this study was to examine the effects of tobacco abstinence and bupropion treatment on cognitive functioning in adult smokers with schizophrenia in the setting of a r and omized , double-blind , placebo-controlled clinical trial of bupropion for smoking cessation . METHOD Fifty-three adults with schizophrenia ( DSM-IV ) took part in a trial of bupropion for smoking cessation . Subjects were enrolled in the study from August 1999 to March 2003 . Forty-five subjects remained in the trial at week 4 ; 41 subjects , 19 taking bupropion and 22 taking placebo , completed the baseline and week 4 cognitive assessment s and were included in the analysis of adjusted effects of abstinence and bupropion treatment on cognitive function . RESULTS Controlling for bupropion treatment and baseline performance , 7 days of tobacco abstinence was associated with slowed motor speed ( finger tapping ) but was not associated with worsening of performance on tests of attention ( AX Continuous Performance Test [ AX-CPT ] ) , verbal learning and memory ( California Verbal Learning Test [ CVLT ] ) , working memory ( digit span ) , or executive function/inhibition ( Stroop ) and was not associated with worsening of any clinical measures . Controlling for abstinence status , bupropion was associated with reduction ( improvement ) in reaction time variability on the AX-CPT and with reduction in perseverative errors on the CVLT . CONCLUSION We conclude that 1 week of tobacco abstinence is associated with slowed motor speed but is not associated with detectable worsening in performance on a range of neuropsychological tests or clinical symptoms in the subset of patients who were able to quit smoking . We also conclude that bupropion treatment may be associated with improvement in variability of attention OBJECTIVE Accepted treatments for cigarette smoking rarely achieve abstinence rates of > 35 % at 1 year . Low rates may reflect failure to provide extended and multifocal treatment for this complex and chronic addiction . Using a chronic disease model of smoking , the authors undertook a study to determine the effects of long-term antidepressant and psychological treatment . METHOD One hundred sixty smokers of > or = 10 cigarettes/day were r and omly assigned to one of four treatment conditions in a two-by-two ( nortriptyline versus placebo by brief versus extended treatment ) design . All subjects received 8 weeks of a transdermal nicotine patch , five group counseling sessions , and active or placebo treatment . Interventions for subjects in brief treatment ended at this point . Subjects in extended treatment continued taking drug or placebo to week 52 and received an additional 9 monthly counseling sessions , with checkup telephone calls midway through each session . Subjects were assessed at baseline and weeks 12 , 24 , 36 , and 52 . The principal outcome variables were repeated abstinence at each assessment after the first over a 1-year period and a point prevalence of 7 days of abstinence . RESULTS At week 52 , point-prevalence abstinence rates with missing subjects imputed as smokers were 30 % for placebo brief treatment , 42 % for placebo extended treatment , 18 % for active brief treatment , and 50 % for active extended treatment . With missing subjects omitted , these rates were 32 % , 57 % , 21 % , and 56 % , respectively . CONCLUSIONS Comprehensive extended treatments that combine drug and psychological interventions can produce consistent abstinence rates that are substantially higher than those in the literature This study examined the role of dopaminergic genes in prospect i ve smoking cessation and response to bupropion treatment in a placebo-controlled clinical trial . Smokers of European ancestry ( N=418 ) provided blood sample s for genetic analysis and received either bupropion or placebo ( 10 weeks ) plus counseling . Assessment s included the dopamine D2 receptor ( DRD2 ) genotype , dopamine transporter ( SLC6A3 ) genotype , demographic factors , and nicotine dependence . Smoking status was verified at the end of treatment ( EOT ) and at 6-month follow-up . The results provided evidence for a significant DRD2 * SLC6A3 interaction effect on prolonged smoking abstinence and time to relapse at EOT , independent of treatment condition . Such effects were no longer significant at 6-month follow-up , however . These results provide the first evidence from a prospect i ve clinical trial that genes that alter dopamine function may influence smoking cessation and relapse during the treatment phase OBJECTIVES In healthy smokers , antidepressants can double the odds of cessation . Because of its four times lower costs and comparable efficacy in healthy smokers , nortriptyline appears to be favourable compared to bupropion . We assessed which of both drugs was most effective and cost-effective in stopping smoking after 1 year compared with placebo among smokers at risk or with existing chronic obstructive pulmonary disease ( COPD ) . METHODS A total of 255 participants , aged 30 - 70 years , received smoking cessation counselling and were assigned bupropion , nortriptyline or placebo r and omly for 12 weeks . Prolonged abstinence from smoking was defined as a participant 's report of no cigarettes from week 4 to week 52 , vali date d by urinary cotinine . Costs were calculated using a societal perspective and uncertainty was assessed using the bootstrap method . RESULTS The prolonged abstinence rate was 20.9 % with bupropion , 20.0 % with nortriptyline and 13.5 % with placebo . The differences between bupropion and placebo [ relative risk ( RR ) = 1.6 ; 95 % confidence interval ( CI ) 0.8 - 3.0 ] and between nortriptyline and placebo ( RR = 1.5 ; 95 % CI 0.8 - 2.9 ) were not significant . Severity of airway obstruction did not influence abstinence significantly . Societal costs were 1368 euros ( 2.5th-97.5th percentile 193 - 5260 ) with bupropion , 1906 euros ( 2.5th-97.5th 120 - 17 761 ) with nortriptyline and 1212 euros ( 2.5th-97.5th 96 - 6602 ) with placebo . Were society willing to pay more than 2000 euros for a quitter , bupropion was most likely to be cost-effective . CONCLUSIONS Bupropion and nortriptyline seem to be equally effective , but bupropion appears to be more cost-effective when compared to placebo and nortriptyline . This impression holds using only health care costs . As the cost-effectiveness analyses concern some uncertainties , the results should be interpreted with care and future studies are needed to replicate the findings We monitored the emergence of major depression ( MDD ) during treatment for nicotine dependence among 224 smokers . MDD was assessed on three occasions during the course of treatment with the mood disorders portion of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders ( SCID ) , fourth edition ( DSM-IV ) . Out of 224 participants , 20 % had suffered a past episode of MDD , 18 % of males and 22 % of females . Four percent ( n=10 ) experienced onset of MDD during the course of the study , four males and six females . Only 2 of the 10 cases managed to achieve abstinence at end of treatment . Those who reported large increases in depression symptoms between baseline and end of treatment ( Week 10 ) were less likely to be abstinent at 26-week follow-up . The evidence indicates that those who treat nicotine dependence must be prepared to monitor and respond to the emergence of depression associated with treatment OBJECTIVE Since attention-deficit/hyperactivity disorder ( ADHD ) is a well-documented risk factor for smoking and bupropion has been shown to be effective for smoking cessation , we tested the efficacy of bupropion as a prophylactic agent for the prevention of smoking in children and adolescents with ADHD . METHOD We conducted a longitudinal , r and omized , double-blind , placebo-controlled , parallel-group study of bupropion at a large , urban , outpatient medical center . Recruitment began in April 1999 , and the last subject was followed until September 2004 . Patients were nonsmoking youth , of both sexes , between 9 and 18 years of age , with DSM-IV ADHD . After r and om assignment to either bupropion or placebo , subjects were assessed weekly for 8 weeks , biweekly for 4 weeks , and monthly thereafter for up to 6.5 years ( mean 12 months ) . Also , patients received treatment with psychostimulants for ADHD symptoms as needed . To assess smoking , we used an assay of cotinine in urine . RESULTS Fifty-seven subjects ( 28 receiving bupropion and 29 receiving placebo ) were r and omly assigned and included in the analysis . No differences were found between the bupropion and placebo groups on demographic factors . About half of each group was treated with stimulants for ADHD . Statistical separation between bupropion and placebo in the rate of smoking initiation or continued smoking was not demonstrated . However , secondary post hoc analyses revealed that concurrent stimulant treatment was significantly associated with a lower rate of smoking onset ( hazard ratio [ HR ] = 0.2 , 95 % CI = 0.08 to 0.89 ; z = -2.2 , p = .03 ) and a lower rate of continued smoking ( HR = 0.3 , 95 % CI = 0.11 to 0.85 ; z = -2.3 , p = .02 ) . CONCLUSION While bupropion was not associated with a lower rate of smoking in youth with ADHD , post hoc analyses suggest that stimulant treatment was . Future controlled studies should investigate the role of stimulants in the prevention of smoking in children and adolescents with ADHD INTRODUCTION This study examined the efficacy and safety of selegiline transdermal system ( STS ) and brief repeated behavioral intervention ( BRBI ) for smoking cessation in heavy smokers . We hypothesized that the quit rate of subjects who received STS and BRBI would be significantly greater than that of those who received placebo patch and BRBI . METHODS This was a double-blind , placebo-controlled parallel-group study in which 246 men and women were r and omized to receive either STS ( n = 121 ) or placebo patch ( n = 125 ) for 9 weeks . Recruitment targeted heavy smokers , defined as individuals with self-reported use of ≥15 cigarettes/day in the 30 days prior to enrollment , who had smoked cigarettes for the past 5 years , and had an expired CO level ≥9 ppm during screening . RESULTS Although STS was well tolerated , the overall results indicated that STS with BRBI was not more effective than placebo plus BRBI for smoking cessation ( p = .58 ) . CONCLUSIONS The results are discussed in relation to interventions for heavy smokers . Although 2 trials using oral selegiline both showed trends toward improved abstinence , these results indicate that STS with BRBI was not an effective aid for smoking cessation at the end of treatment ( 10 weeks ) , 14 , or 26 weeks Several studies have documented the effectiveness of bupropion for smoking cessation , yet little is known about the mechanisms by which it facilitates abstinence . In this placebo-controlled r and omized trial . We examined whether bupropion 's effects on cessation were mediated by changes in withdrawal and /or negative or positive affect ( PA ) . Two hundred and fifty-one smokers received 10-week treatment with bupropion or placebo , plus behavioral counseling . Changes in affect and withdrawal symptoms from pre-quit to 1 week post quit were examined as mediating variables in structural equation models . Cotinine-verified 7-day point prevalence cessation rates at the end of treatment ( 8-weeks post quit date ) were 48 % for bupropion and 29 % for placebo ( P=0.001 ) . There were significant treatment effects on withdrawal and negative affect ( NA ) ; however , only change in NA predicted cessation . In a path model , change in NA was a significant mediator of bupropion 's effects on cessation . However , the proportion of variance accounted for by this mediator was small , suggesting that other unmeasured factors play an important role . Laboratory-based paradigms may be useful to identify other mediators of bupropion 's effects , thereby pointing to mechanisms of effect that can be bolstered in future treatment studies OBJECTIVES Identification of individual characteristics that predict successful smoking cessation treatment has been limited to studies with mostly white participants . This study identifies factors that predict successful quitting among African-Americans participating in a smoking cessation trial . METHODS Twenty-one baseline variables were analyzed as potential predictors from a double-blind placebo-controlled , r and omized trial that used bupropion SR for smoking cessation among 600 African-American smokers . Chi-square tests , two sample t tests , and multiple logistic regression procedures were employed to identify predictors of 7-day abstinence among the 535 participants who completed the 7-week medication phase . RESULTS Univariate predictors of cessation were receiving bupropion ( P < 0.0001 ) , not smoking menthol cigarettes ( P = 0.0062 ) , smoking after 30 min of waking ( P < 0.0001 ) , older age ( P = 0.0085 ) , smoking fewer cigarettes per day ( P = 0.0038 ) , and lower cotinine levels ( P = 0.0002 ) . Logistic regression identified three significant independent predictors . Participants who received bupropion treatment were more than twice as likely to quit smoking at the end of treatment compared to participants who received placebo ( OR = 2.62 ; 95 % CI = 1.77 - 3.88 , P < 0.0001 ) , while smoking within 30 min of waking ( OR = 0.40 ; 95 % CI = 0.25 - 0.62 , P < 0.0001 ) and higher salivary cotinine levels at baseline ( OR = 0.799 ; 95 % CI = 0.629 - 0.922 , P < 0.0001 ) reduced the likelihood of quitting . CONCLUSIONS This is the first report identifying predictors of smoking cessation among African-Americans participating in a clinical trial . Results indicate that , aside from bupropion treatment , various indicators of addiction were the strongest predictors . While this is similar to findings among white smokers , thresholds of addiction may need to be adjusted for African-American smoking patterns . Additional studies focused on diverse population s are needed to improve treatment approaches and to identify population -specific factors that are important for treatment-matching approaches Abstract : The purpose of this study was to assess the effect of bupropion on cytochrome P450 2D6 ( CYP2D6 ) activity . Twenty-one subjects completed this repeated- measures study in which dextromethorphan ( 30-mg oral dose ) was administered to smokers at baseline and after 17 days of treatment with either bupropion sustained-release ( 150 mg twice daily ) or matching placebo . Subjects quit smoking 3 days before the second dextromethorphan administration . To assess CYP2D6 activity , urinary dextromethorphan/dextrorphan metabolic ratios were calculated after an 8-hour urine collection . Thirteen subjects received bupropion , and 8 received placebo . In those receiving active medication , the dextromethorphan/dextrorphan ratio increased significantly at the second assessment relative to the first ( 0.012 ± 0.012 vs. 0.418 ± 0.302 ; P < 0.0004 ) . No such change was observed in those r and omized to placebo ( 0.009 ± 0.010 vs. 0.017 ± 0.015 ; P = NS ) . At baseline , all subjects were phenotypically extensive CYP2D6 metabolizers ( metabolic ratio < 0.3 ) ; after treatment , 6 of 13 subjects receiving bupropion , but none of those receiving placebo , had metabolic ratios consistent with poor CYP2D6 metabolizers . Bupropion is therefore a potent inhibitor of CYP2D6 activity , and care should be exercised when initiating or discontinuing bupropion use in patients taking drugs metabolized by CYP2D6 Recent research has demonstrated there is a high prevalence of weight concerns in smokers and that smokers with weight concerns may respond poorly to treatment for tobacco dependence . Most studies have focused only on females or have consisted of small sample s. In this study of a 12-week r and omized trial of nicotine inhaler , bupropion or both for smoking cessation , 50 % of the 1012 female smokers and 26 % of the 680 male smokers , at study entry , were weight concerned . In examining the impact of weight concerns on the 12-week point-prevalence smoking abstinence , 26 % of non-weight-concerned smokers quit smoking compared to 22 % of weight-concerned smokers ( p=0.06 ) . This study , which includes a large sample of both genders , provides further evidence that approximately half of females who are seeking smoking cessation treatment are weight concerned and that one quarter of male smokers are weight concerned . Additionally , being weight concerned may impact the short-term success rates of stopping smoking using pharmacotherapy AIMS The effect of successful and unsuccessful smoking cessation on depressive mood , anxiety- and suicide-related outcomes is unclear . The aim of this secondary analysis was to explore the relationship between abstinence status and these outcomes . DESIGN Cohort of adult smokers attempting to stop smoking . Smoking status was assessed by a daily diary ; depressed mood , anxiety and suicidal tendencies by the Hamilton Depression Rating Scale ( HDRS ) . The association of complete and point-prevalence abstinence with the HDRS variables was assessed using multi-level linear regression models . SETTING R and omized trial of sertraline versus placebo for smoking cessation with weekly behavioural support provided in a clinic . PARTICIPANTS A total of 133 adult smokers with past major depression . FINDINGS Pre-quit mood scores did not predict smoking status post-quit day . Both continuous and point-prevalence abstainers had significantly lower total HDRS , suicide and anxiety scores , adjusted for all potential confounders , during the period following quit day than did non-abstainers who experienced a significant mood deterioration . There was a significant effect of sertraline on post-quit HDRS scores but not on abstinence . CONCLUSIONS Contrary to expectation , smoking abstinence among smokers with a history of major depression did not lead to increase in depression , anxiety or suicide ideation ; however , failed quit attempts did . Persisting with a quit attempt while unable to achieve abstinence may be associated with mood deterioration Objective Many cancer patients continue to smoke post diagnosis , yet there have been few smoking cessation trials for this population . Depression , which is prevalent among cancer patients , may be a barrier to cessation . Methods This double-blind placebo-controlled trial r and omized 246 cancer patients to 9 weeks of placebo or bupropion , stratifying by pre-treatment depression symptoms . In addition , all patients received transdermal nicotine and behavioral counseling . Primary outcomes were 7-day point-prevalence abstinence , biochemically confirmed , at the end of treatment ( Week 12 ) , and at 6 months post quit day ( Week 27 ) . Additional outcomes included : withdrawal , affect , quality of life , compliance , and side effects . Results There was no main effect of bupropion vs. placebo on abstinence ( Odds Ratio [ OR ] = 1.36 , 95 % CI : 0.38–4.81 , p = .64 ) . Patients with depression symptoms reported significantly lower abstinence rates vs. patients without depression symptoms ( OR = .14 , 95 % CI : 0.02–0.80 , p = .03 ) . Bupropion increased abstinence rates , vs. placebo , more for participants with depression vs. those without depression symptoms . For patients with depression symptoms , bupropion reduced withdrawal symptoms and improved quality of life vs. placebo . Conclusions For patients with depression symptoms , bupropion increases abstinence rates , lowers withdrawal , and increases quality of life . However , abstinence rates among patients with depression symptoms were low vs. patients without depression symptoms , who exhibited similar abstinence rates when treated with bupropion or transdermal nicotine and counseling alone . These results can guide future smoking cessation intervention studies with cancer patients 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 Although bupropion is efficacious for smoking cessation , only a minority of smokers are able to quit . Pharmacogenetic research may improve treatment outcomes through discovery of DNA sequences predictive of successful pharmacotherapy for subgroups of smokers . We investigated variants in the catechol-O-methyltransferase ( COMT ) gene in a smoking cessation trial of bupropion . METHODS A double-blind , placebo-controlled , 10-week trial of bupropion and counseling ( with a 6-month follow-up period ) was conducted at two university-based smoking cessation research programs . Abstinence was biochemically verified at the end of treatment and at 6 months after the target quit date . RESULTS At the end of the treatment phase , statistically significant interaction effects indicated that COMT haplotypes of two SNPs ( rs737865 and rs165599 ) predicted the efficacy of bupropion compared with placebo . This interaction effect was attenuated at 6-month follow-up . CONCLUSIONS COMT haplotypes at rs737865 and rs165599 may predict a favorable outcome for bupropion treatment for smoking cessation . European-American smokers with a G allele at both SNPs may not benefit from bupropion treatment . Small numbers of some COMT haplotypes limit interpretation of response . If study findings are confirmed in additional large studies , COMT genotyping could be applied to identify likely responders to bupropion treatment for smoking cessation We report a re analysis of data from a prior study describing the event history of quitting smoking aided by bupropion , using recurrent-event models to determine the effect of the drug on occurrence of lapses and recoveries from lapse ( resumption of abstinence ) . Data were collected on 1,070 subjects across two similar double-blind r and omized clinical trials of bupropion versus placebo and fitted with separate Cox regression models for lapse and recovery . Analyses were split using discrete time-varying covariates between the treatment ( weeks 1 - 10 ) and follow-up phases ( end of treatment to 12 months ) . Bupropion was associated with slower lapse during treatment for both sexes , and being female was associated with faster lapse across both phases . Drug did not affect time to recovery for males but was associated with faster recovery among females , allowing women to recover as quickly as men . High levels of nicotine dependence did not affect time to lapse but were associated with slower recovery from lapse across treatment and follow-up phases . During the treatment phase , higher levels of baseline depression symptoms had no effect on time to lapse but were associated with slower recovery from lapse . Results highlight the asymmetry in factors preventing lapse versus promoting recovery . Specifically , dependence , depression symptoms , and a sex x drug interaction were found to affect recovery but not lapse . Further research disentangling lapse and recovery events from summary abstinence measures is needed to help us develop interventions that take advantage of bupropion at its best and that compensate where it is weak INTRODUCTION Smoking expectancies are related to smoking consumption and predict smoking cessation . Little is known about whether expectancies change during smoking treatments , consistent with changes in smoking behavior . This study examined reported changes in smoking beliefs during an 8-week smoking cessation trial , which evaluated the safety and efficacy of the monoamine oxidase B inhibitor selegiline hydrochloride versus placebo . METHODS Participants were classified as " Quit " ( n = 18 ) , " Reduced " ( n = 34 ) , or " Not Quit " ( n = 49 ) by 7-day point prevalence abstinence at the end of treatment . Expectancies were assessed at r and omization , 1 week after the target quit date , and at the end of treatment . RESULTS Beliefs about smoking assessed prior to the quit attempt were not associated with cessation outcomes . Participants who quit smoking reported a reduction in expectations that smoking would reduce negative affect , boredom , and cravings , and facilitate social interactions , while participants who did not quit smoking reported an increase in Negative Social Impression beliefs . There were gender differences in beliefs related to Negative Affect Reduction , Negative Physical Feelings , Social Facilitation , and Cravings and significant Gender X Smoking Status interactions for Health Risk and Weight Control beliefs . There were no significant effects of medication on expectancies . DISCUSSION Baseline expectancies were not associated with abstinence outcomes ; however , expectancies changed over time with changes in smoking , and the greatest changes were seen with smoking abstinence . Information about the relationship between smoking beliefs and behaviors may be used to enhance or tailor smoking cessation treatments OBJECTIVE To evaluate bupropion SR for smoking cessation in physicians and nurses . METHODS This double-blind prospect i ve 26-center , 12-country trial r and omized 687 subjects to smoking cessation counselling with bupropion SR or placebo for 7 weeks . The participants were followed for 52 weeks . RESULTS Bupropion SR was superior to placebo ( 50 % vs 40 % , P=0.013 ) on the 4-week primary outcome variable . Due to a high placebo response in this health care population , statistical differences were not maintained after treatment was discontinued . CONCLUSIONS Bupropion SR is effective and well tolerated in health care professionals . Relapse prevention measures are needed to attain long-term abstinence PURPOSE Smoking cessation after myocardial infa rct ion reduces cardiovascular mortality , but many smokers can not quit despite state-of-the-art counseling intervention . Bupropion is effective for smoking cessation , but its safety and efficacy in hospitalized smokers with acute cardiovascular disease is unknown . METHODS A five-hospital r and omized double-blind placebo-controlled trial assessed the safety and efficacy of 12 weeks of sustained-release bupropion ( 300 mg ) or placebo in 248 smokers admitted for acute cardiovascular disease , primarily myocardial infa rct ion and unstable angina . All subjects had smoking counseling in the hospital and for 12 weeks after discharge . Cotinine-vali date d 7-day tobacco abstinence , cardiovascular mortality , and new cardiovascular events were assessed at 3 months ( end-of-treatment ) and 1 year . RESULTS Vali date d tobacco abstinence rates in bupropion and placebo groups were 37.1 % vs 26.8 % ( OR 1.61 , 95 % CI , 0.94 - 2.76 ; P=.08 ) at 3 months and 25.0 % vs 21.3 % ( OR , 1.23 , 95 % CI , 0.68 - 2.23 , P=.49 ) at 1 year . The adjusted odds ratio , after controlling for cigarettes per day , depression symptoms , prior bupropion use , hypertension , and length of stay , was 1.91 ( 95 % CI , 1.06 - 3.40 , P=.03 ) at 3 months and 1.51 ( 95 % CI , 0.81 - 2.83 ) at 1 year . Bupropion and placebo groups did not differ in cardiovascular mortality at 1 year ( 0 % vs 2 % ) , in blood pressure at follow-up , or in cardiovascular events at end-of-treatment ( 16 % vs 14 % , incidence rate ratio [IRR]1.22 ( 95 % CI : 0.64 - 2.33 ) or 1 year ( 26 % vs 18 % , IRR 1.56 , 95 % CI 0.91 - 2.69 ) . CONCLUSIONS Bupropion improved short-term but not long-term smoking cessation rates over intensive counseling and appeared to be safe in hospitalized smokers with acute cardiovascular disease OBJECTIVE To determine the relationship between joint variation in 2 dopaminergic genes and the likelihood of nonsmoking following treatment with bupropion sustained release ( SR ) . DESIGN Three hundred twenty-three participants in a bupropion SR smoking cessation effectiveness trial with 12-month follow-up were genotyped for variants of dopamine receptor gene DRD2 and dopamine transporter SLC6A3 . MAIN OUTCOME MEASURES Self-reported 7-day point prevalence of nonsmoking . RESULTS Neither genotype alone was associated with 7-day point-prevalent nonsmoking at the 12-month follow-up . However , in the presence of the DRD2 A1 allele , SLC6A3 status was significantly associated with the likelihood of nonsmoking at the 12-month follow-up ( individuals with DRD2 A1 + and SLC6A3 9- were more likely to be smoking ) . In the absence of the DRD2 A1 allele , the association between SLC6A3 status and nonsmoking was nonsignificant . CONCLUSION Although these results are suggestive , a more compelling test is needed of the hypothesis that dopaminergic gene interaction underlies , in part , the likelihood of smoking following treatment with bupropion SR . Most likely this will come from larger studies involving prospect i ve r and omization to treatment based on genotype Rationale Individuals with schizophrenia have high smoking-related morbidity and mortality rates and need powerful and innovative smoking cessation interventions . Objectives This proof-of-concept study investigated the feasibility and initial efficacy of combining a contingency management intervention with bupropion to reduce smoking in people with schizophrenia . Methods Using a double-blind , placebo-controlled , between-groups design , 57 non-treatment-seeking participants were r and omized to receive 300 mg/day bupropion or placebo . One week later , participants were r and omized to a contingency management ( CM ) intervention in which reductions in urinary cotinine levels were reinforced , or a non-contingent reinforcement ( NR ) condition in which session attendance was reinforced , regardless of cotinine level . Over the 22-day study period , participants visited the laboratory approximately three times per week to provide urine sample s for analysis of cotinine levels , to give breath sample s for analysis of carbon monoxide ( CO ) levels , and to report number of cigarettes smoked per day , nicotine withdrawal symptoms , cigarette craving , and psychiatric symptoms . Results Cotinine and CO levels significantly decreased during the study period in participants r and omized to the CM condition , but not the NR condition . Bupropion did not reduce cotinine levels or increase the efficacy of CM . Cigarette craving and psychiatric symptom levels significantly decreased during the study in all groups . Conclusions The results of this study indicate the efficacy and feasibility of this CM intervention for reducing smoking in individuals with schizophrenia UNLABELLED There are different modalities for management of Nicotine dependence , but it is still inconclusive which is the best modality for the treatment of Nicotine dependence syndrome ( NDS ) . In this background the present study was carried out to assess the efficacy and to compare different modalities for the treatment of NDS . METHODS Patients diagnosed as NDS as per ICD-10 were taken up for study . These patients were administered proforma to elicit sociodemographic details , Fagerstrom test for Nicotine Dependence , Question naire of Smoking Urges-Brief and breath analysis was done using carbon monoxide meter . Assessment was done at base line and at weekly follow-ups for 12 weeks . Patients were divided into six groups r and omly . Group A received BUP at a dose of 150mg/day for 3 days ; subsequently increased to 300mg/day , Group B : for initial 6 weeks Nicotine gum of 4 mg every 1 - 2 hourly was used and next 6 weeks every 2 - 4 hourly was used , Group C : BI , Group D : BI+BUP , Group E : BI+NRT , Group F received BUP+NRT+BI . RESULTS The quit rates at end of the study were BUP-30 % , NRT-26.66 % , BI-23.33 % , BI+BUP-43.33 % , BI+NRT-33.33 % , and BI+BUP+NRT-50 % . BI+BUP+NRT had 2 - 3 times more quit rates than the individual modality treatment group . CONCLUSION There was no statistically significant difference between the study groups , but there was clinical difference in quit rates . Among the groups BI+BUP+NRT had higher quit rates compared to other groups . Combination modalities yield better quit rates than individual modalities 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 To assess the effectiveness of moclobemide on smoking cessation and abstinence in heavy , dependent smokers . There is a strong association between smoking and depression , especially in dependent smokers . It was hypothesized that smoking is a self‐medication to treat depression . Cigarette smoke has monoamine oxidase (MAO)‐inhibitory properties , and smokers have lower MAO activity than nonsmokers Abstract : The objective of this study was to examine the efficacy of bupropion for smoking cessation in patients with schizophrenia . Adults with schizophrenia who smoked more than 10 cigarettes per day and wished to try to quit smoking were recruited from community mental health centers , enrolled in a 12-week group cognitive behavioral therapy intervention , and r and omly assigned to receive either bupropion sustained-release 300 mg/d or identical placebo . Fifty-three adults , 25 on bupropion and 28 on placebo , were r and omized , completed at least 1 postbaseline assessment and were included in the analysis . The primary outcome measures were 7-day point prevalence abstinence in the week after the quit date ( week 4 ) and at the end of the intervention ( week 12 ) . Subjects in the bupropion group were significantly more likely to be abstinent for the week after the quit date ( 36 % [ 9/25 ] vs. 7 % [ 2/28 ] , P = 0.016 ) and at end of the intervention ( 16 % [ 4/25 ] vs. 0 % , P = 0.043 ) . Subjects in the bupropion group also had a higher rate of 4-week continuous abstinence ( weeks 8 - 12 ) ( 16 % [ 4/25 ] vs. 0 % , P = 0.043 ) and a longer duration of abstinence ( 4.2 [ 3.2 ] weeks vs. 1.8 [ 0.96 ] weeks , t = 2.30 , P = 0.037 ) . The effect of bupropion did not persist after discontinuation of treatment . Subjects in the bupropion group had no worsening of clinical symptoms and had a trend toward improvement in depressive and negative symptoms . We conclude that bupropion does not worsen clinical symptoms of schizophrenia and is modestly effective for smoking cessation in patients with schizophrenia . The relapse rate is high after treatment discontinuation OBJECTIVES The purpose of this study was to examine smoking cessation rates among smokers with AMI to determine whether bupropion , started in-hospital , is safe and can improve cessation rates at 1 year . BACKGROUND Bupropion doubles quit rates in otherwise healthy smokers and patients with stable cardiovascular disease . Although 2 previous trials examined the use of bupropion in patients hospitalized with acute cardiovascular disease , these studies have been inconclusive with respect to its safety and efficacy in patients with acute myocardial infa rct ion ( AMI ) . METHODS We conducted a multicenter , double-blind , placebo-controlled , r and omized trial in smokers hospitalized with AMI . Participants received bupropion or placebo for 9 weeks and were followed for 12 months . Both groups received low-intensity counseling . Point prevalence abstinence was assessed by 7-day recall and biochemical validation of expired carbon monoxide . RESULTS A total of 392 patients were r and omized ( mean age 53.9 ± 10.3 years ) ; 83.5 % were male ; 64.9 % had ST-segment elevation myocardial infa rct ion ) . Patients smoked a mean of 23.2 ± 10.6 cigarettes/day for a mean of 32.9 ± 12.4 years . At 12 months , point prevalence abstinence rates were 37.2 % in the bupropion group and 32.0 % in the placebo group ( p = 0.33 ; % difference after adjusting for between center differences 3.9 % ) . Continuous abstinence rates were 26.8 % and 22.2 % , respectively ( p = 0.34 ) . Major adverse cardiac event rates were similar ( 13.0 % vs. 11.0 % , respectively ; p = 0.64 ) . CONCLUSIONS Two-thirds of patients return to smoking by 12 months after AMI . Bupropion is well tolerated and seems to be safe to use in the immediate post-AMI period . However , bupropion is not effective for smoking cessation in patients post-AMI Although bupropion and nicotine replacement therapy ( NRT ) are efficacious tobacco dependence treatments , there is substantial interindividual variability in therapeutic response and most smokers relapse . Pharmacogenetics research may improve treatment outcomes by identifying genetic variants predictive of therapeutic response . We investigated the roles of two functional genetic variants in the dopamine D2 receptor ( DRD2 ) gene in response to pharmacotherapy for tobacco dependence among participants in two r and omized clinical trials with a 6-month follow-up period : a double-blind placebo-controlled trial of bupropion ( n=414 ) and an open label trial of transdermal nicotine vs nicotine nasal spray ( n=368 ) . At the end of the treatment phase , a statistically significant ( p=0.01 ) interaction between the DRD2 − 141C Ins/Del genotype and treatment indicated a more favorable response to bupropion among smokers homozygous for the Ins C allele compared to those carrying a Del C allele . By contrast , smokers carrying the Del C allele had statistically significantly ( p=0.006 ) higher quit rates on NRT compared to those homozygous for the Ins C allele , independent of NRT type . The C957 T variant was also associated ( p=0.03 ) with abstinence following NRT . These results suggest that bupropion may be the preferred pharmacologic treatment for smokers homozygous for the DRD2 − 141 Ins C allele , while NRT may be more beneficial for those who carry the Del C allele . Study findings require confirmation in additional larger sample s before they are applied in practice Bupropion hydrochloride is effective in promoting long-term abstinence from smoking and may reduce risk for relapse through attenuation of withdrawal symptoms and craving . Bupropion is a weak dopamine reuptake inhibitor , and individual genetic variation in the dopamine D2 receptor has been associated with nicotine dependence in case-control studies . Thirty smokers were r and omly assigned to bupropion or placebo and interviewed using the Minnesota Nicotine Withdrawal Scale on two occasions : prior to starting medication and after 14 days on bupropion or placebo . The individual symptoms of craving , irritability , and anxiety were significantly reduced in the bupropion group , whereas no withdrawal symptoms were diminished in the placebo group . Within the bupropion group , subgroup analyses with stratification by genotype demonstrated that craving , irritability , and anxiety were significantly attenuated only among subjects with DRD2-Taq1 A2/A2 genotypes . In the DRD2-Taq1 A1/A1 and A1/A2 groups , no significant reduction was seen in any individual symptom of the nicotine withdrawal syndrome . These data suggest that bupropion attenuates specific symptoms of the nicotine withdrawal syndrome and that this effect may be modified by genotype for the dopamine D2 receptor The objective of the present study was to test whether confronting smokers with previously undetected chronic obstructive pulmonary disease ( COPD ) increases the rate of smoking cessation . In total , 296 smokers with no prior diagnosis of COPD were detected with mild-to-moderate airflow limitation by means of spirometry and r and omly allocated to : confrontational counselling by a nurse with nortriptyline for smoking cessation ( experimental group ) ; regular counselling by a nurse with nortriptyline ( control group 1 ) ; or “ care as usual ” for smoking cessation by the general practitioner ( control group 2 ) . Only the experimental group was confronted with their abnormal spirometry ( mean forced expiratory volume in one second ( FEV1 ) post-bronchodilator 80.5 % predicted , mean FEV1/forced vital capacity post-bronchodilator 62.5 % ) . There was no difference in cotinine-vali date d prolonged abstinence rate between the experimental group ( 11.2 % ) and control group 1 ( 11.6 % ) from week 5–52 ( odds ratio ( OR ) 0.96 , 95 % confidence interval ( CI ) 0.43–2.18 ) . The abstinence rate was approximately twice as high in the experimental group compared with control group 2 ( 5.9 % ) , but this difference was not statistically significant ( OR 2.02 , 95 % CI 0.63–6.46 ) . The present study did not provide evidence that the confrontational approach increases the rate of long-term abstinence from smoking compared with an equally intensive treatment in which smokers were not confronted with spirometry . The high failure rates ( ≥88 % ) highlight the need for treating tobacco addiction as a chronic relapsing disorder The objective of this study was to examine whether there is a benefit of adding bupropion SR to high-dose combination nicotine replacement therapy ( NRT ) and weekly group cognitive behavioral therapy ( CBT ) for smoking reduction or cessation in schizophrenia . Fifty-one adult smokers with schizophrenia were r and omly assigned to a 12-week trial of bupropion SR 300 mg/d or placebo added to transdermal nicotine patch , nicotine polacrilex gum , and CBT . The treatment goal was smoking cessation . The primary outcome measure was biochemically confirmed 7-day point-prevalence of 50 % to 100 % smoking reduction at week 12 . Secondary outcomes were biochemically confirmed tobacco abstinence and change from baseline in expired air carbon monoxide ( CO ) and psychiatric symptoms . Subjects on bupropion + NRT had a greater rate of 50 % to 100 % smoking reduction at weeks 12 ( 60 % vs. 31 % ; P = 0.036 ) and 24 , a lower expired air CO in the treatment and follow-up periods , ( F = 13.8 ; P < 0.001 ) and a greater continuous abstinence rate at week 8 , before NRT taper , ( 52 % vs. 19 % ; P = 0.014 ) . However , relapse rates in subjects on bupropion + dual NRT were 31 % during NRT taper ( weeks 8 - 12 ) and 77 % at the 12-month follow-up . Abstinence rates did not differ by treatment group at weeks 12 ( 36 % vs. 19 % ) , 24 ( 20 % vs. 8 % ) , or 52 ( 12 % vs. 8 % ) . Because abstinence rates were high during treatment with combination pharmacotherapy and relapse rates were very high during taper and after discontinuation of treatment , study of longer term treatment with combination pharmacotherapy and CBT for sustained abstinence is warranted in those who attain initial abstinence with this intervention BACKGROUND Little is known about the effectiveness of bupropion SR for smoking cessation outside the context of clinical efficacy trials , where in-person screening and treatment occur at a higher level than provided in a typical health care system . This article describes the methods for recruitment , screening for exclusions , and result ing sample in a field trial of bupropion SR undertaken in a managed-care setting . METHODS A total of 2979 telephone interviews were conducted to screen and identify eligible volunteers using a detailed protocol that allowed for consultation with study physicians when necessary . The volunteers ' primary care physicians were given the option to override their eligibility , and pharmacy data bases were used to verify medication reporting . RESULTS A total of 1909 ( 64 % ) volunteers were considered eligible for the study . The most common reason for exclusion was use of contraindicated medications ( 32 % ) , followed by recent use of one of the behavioral cessation programs ( 14 % ) , brain injury that reduced seizure threshold ( 14 % ) , current depression ( 14 % ) , and high levels of alcohol use ( 13 % ) . CONCLUSIONS The methods used in this field trial show that it is possible to enroll subjects in an effectiveness trial that is successful from the st and point of the consumer , provider , and health care system This study reports an experimental , r and omized controlled clinical trial comparing three treatments for smoking cessation : sustained-release bupropion , nicotine patch , and combination nicotine and bupropion , to a counseling-only control group ( N = 140 ) , for smoking sailors aboard seven Navy ships . The purpose was to determine the effectiveness of different pharmcotherapies used in smoking cessation programs . Continuous abstinence was defined as the percentage of subjects who did not smoke since the quit date assessed at 6 and 12 months and having an expired carbon monoxide concentration of < 10 ppm at educational sessions 2 , 3 , and 4 . Nine subjects dropped out of the study , and 40 subjects were lost to follow-up . Eleven percent ( 15/140 subjects ) had continuous abstinence at 12 months . The abstinence rates at 12 months were 47 % in the control group , as compared with 27 % in the nicotine patch/bupropion group , 20 % in the nicotine patch group , and 7 % in the bupropion group AIMS To determine , in the context of a trial in which counseling did not improve smoking cessation outcomes , whether this was due to a failure of the conceptual theory identifying treatment targets or the action theory specifying interventions . DESIGN Data from a r and omized clinical trial of smoking cessation counseling and bupropion SR were su bmi tted to multi-level modeling to test whether counseling influenced real-time reports of cognitions , emotions and behaviors , and whether these targets predicted abstinence . SETTING Center for Tobacco Research and Intervention , Madison , WI . PARTICIPANTS A total of 403 adult , daily smokers without contraindications to bupropion SR use . Participants were assigned r and omly to receive individual counseling or no counseling and a 9-week course of bupropion SR or placebo pill . Cessation counseling was delivered in eight 10-minute sessions focused on bolstering social support , motivation , problem-solving and coping skills . MEASUREMENTS Pre- and post-quit ecological momentary assessment s of smoking behavior , smoking triggers , active prevention and coping strategies , motivation to quit , difficulty quitting and reactions to initial lapses . FINDINGS Counseling prompted avoidance of access to cigarettes , improved quitting self-efficacy , reduced perceived difficulty of quitting over time and protected against guilt and demoralization following lapses . Results also supported the importance of limiting cigarette access , receiving social support , strong motivation and confidence and easing withdrawal distress during cessation efforts . Quitting self-efficacy and perceived difficulty quitting may partially mediate counseling effects on abstinence . CONCLUSIONS Smoking cessation counseling may work by supporting confidence about quitting and reducing perceived difficulty quitting . Counseling did not affect other targets that protect against relapse CONTEXT Little direct evidence exists on the relative efficacies of different smoking cessation pharmacotherapies , yet such evidence is needed to make informed decisions about their clinical use . OBJECTIVE To assess the relative efficacies of 5 smoking cessation pharmacotherapy interventions using placebo-controlled , head-to-head comparisons . DESIGN A r and omized , double-blind , placebo-controlled clinical trial . SETTING Two urban research sites . PATIENTS One thous and five hundred four adults who smoked at least 10 cigarettes per day during the past 6 months and reported being motivated to quit smoking . Participants were excluded if they reported using any form of tobacco other than cigarettes ; current use of bupropion ; having a current psychosis or schizophrenia diagnosis ; or having medical contraindications for any of the study medications . INTERVENTIONS Participants were r and omized to 1 of 6 treatment conditions : nicotine lozenge , nicotine patch , sustained-release bupropion , nicotine patch plus nicotine lozenge , bupropion plus nicotine lozenge , or placebo . In addition , all participants received 6 individual counseling sessions . MAIN OUTCOME MEASURES Biochemically confirmed 7-day point-prevalence abstinence assessed at 1 week after the quit date ( postquit ) , end of treatment ( 8 weeks postquit ) , and 6 months postquit . Other outcomes were initial cessation , number of days to lapse , number of days to relapse , and latency to relapse after the first lapse . RESULTS All pharmacotherapies differed from placebo when examined without protection for multiple comparisons ( odds ratios , 1.63 - 2.34 ) . With such protection , only the nicotine patch plus nicotine lozenge ( odds ratio , 2.34 , P < .001 ) produced significantly higher abstinence rates at 6-month postquit than did placebo . CONCLUSION While the nicotine lozenge , bupropion , and bupropion plus lozenge produced effects that were comparable with those reported in previous research , the nicotine patch plus lozenge produced the greatest benefit relative to placebo for smoking cessation BACKGROUND Tobacco use is responsible for a large proportion of the total disease burden from tuberculosis . Pakistan is one of the 10 high-burden countries for both tuberculosis and tobacco use . OBJECTIVE To assess the effectiveness of a behavioral support intervention and bupropion in achieving 6-month continuous abstinence in adult smokers with suspected pulmonary tuberculosis . DESIGN Cluster r and omized , controlled trial . ( Current Controlled Trials : IS RCT N08829879 ) SETTING Health centers in the Jhang and Sargodha districts in Pakistan . PATIENTS 1955 adult smokers with suspected tuberculosis . INTERVENTION Health centers were r and omly assigned to provide 2 brief behavioral support sessions ( BSS ) , BSS plus 7 weeks of bupropion therapy ( BSS+ ) , or usual care . MEASUREMENTS The primary end point was continuous abstinence at 6 months after the quit date and was determined by carbon monoxide levels in patients . Secondary end points were point abstinence at 1 and 6 months . RESULTS Both treatments led to statistically significant relative risks ( RRs ) for abstinence compared with usual care ( RR for BSS+ , 8.2 [ 95 % CI , 3.7 to 18.2 ] ; RR for BSS , 7.4 [ CI , 3.4 to 16.4 ] ) . Equivalence between the treatments could not be established . In the BSS+ group , 275 of 606 patients ( 45.4 % [ CI , 41.4 % to 49.4 % ] ) achieved continuous abstinence compared with 254 of 620 ( 41.0 % [ CI , 37.1 % to 45.0 % ] ) in the BSS group and 52 of 615 ( 8.5 % [ CI , 6.4 % to 10.9 % ] ) in the usual care group . There was substantial heterogeneity of program effects across clusters . LIMITATIONS Imbalances in the urban and rural proportions and smoking habits among treatment groups , and inability to confirm adherence to bupropion treatment and vali date longer-term abstinence or the effect of smoking cessation on tuberculosis outcomes . CONCLUSION Behavioral support alone or in combination with bupropion is effective in promoting cessation in smokers with suspected tuberculosis . PRIMARY FUNDING SOURCE International Development Research Centre We analyzed pooled data from two comparable r and omized placebo-controlled clinical trials of bupropion pharmacotherapy for smoking cessation for which data on DRD2 Taq1A genotype were available . A total of 722 smokers across the two trials were r and omized to 10 weeks of sustained-release bupropion hydrochloride or placebo . General estimating equation analysis demonstrated a significant gene x drug interaction ( B = 0.87 , SE = 0.34 , p = .009 ) . Smokers with the A2/A2 genotype using bupropion were more than three times as likely , relative to placebo , to be abstinent at end of treatment ( 35.2 % vs. 15.1 % ; OR = 3.25 , 95 % CI 2.00 - 5.28 ) and at 6 months of follow-up ( 26.7 % vs. 12.2 % ; OR = 2.81 , 95 % CI 1.66 - 4.77 ) , which was attenuated by 12 months ( 16.3 % vs. 10.7 % ; OR = 1.70 , 95 % CI 0.95 - 3.05 ) . We found no significant benefit of bupropion relative to placebo on smoking cessation outcomes at any time point in participants with A1/A1 or A1/A2 genotypes . These data suggest that bupropion may be effective for smoking cessation only in a subgroup of smokers with the DRD2 Taq1 A2/A2 genotype Limited data exist regarding the management of patients with acute coronary syndrome ( ACS ) in high-income countries compared with low/middle-income countries . We aim ed to compare in-hospital trends of revascularization and prescription of medications at discharge in patients with ACS from high-income ( Canada and United States ) and low/middle-income ( India , Iran , Pakistan , and Tunisia ) countries . Data from a double-blind , placebo-controlled , r and omized trial investigating the effect of bupropion on smoking cessation in patients after an enzyme-positive ACS was used for our study . A total of 392 patients , 265 and 127 from high-income and from low/middle-income countries , respectively , were enrolled . Patients from high-income countries were older , and were more likely to have diagnosed hypertension and dyslipidemia . During the index hospitalization , patients from high-income countries were more likely to be treated by percutaneous coronary intervention ( odds ratio [ OR ] 19.7 , 95 % confidence interval [ CI ] 10.5 to 37.0 ) . Patients with ST elevation myocardial infa rct ion from high-income countries were more often treated by primary percutaneous coronary intervention ( OR 16.3 , 95 % CI 6.3 to 42.3 ) in contrast with thrombolytic therapy ( OR 0.24 , 95 % CI 0.14 to 0.41 ) . Patients from high-income countries were also more likely to receive evidence -based medications at discharge ( OR 2.32 , 95 % CI 1.19 to 4.52 , a composite of aspirin , clopidogrel , and statin ) . In conclusion , patients with ACS in low/middle-income countries were less likely to be revascularized and to receive evidence -based medications at discharge . Further studies are needed to underst and the underutilization of procedures and evidence -based medications in low/middle-income countries OBJECTIVE Adolescent overweight and obesity and smoking continue to be very important health challenges because of their lasting effects on overall health . Weight gain after smoking cessation is a barrier to quitting as well as a negative consequence to health . This study reports changes in the body mass index ( BMI ) z-scores of adolescent smokers participating in a dose-ranging clinical trial of bupropion SR ( 150 mg/day and 300 mg/day ) for smoking cessation . METHODS A total of N = 296 adolescent smokers ( placebo n = 100 , 150 mg/day n = 101 , 300 mg/day n = 95 ) with a BMI z-score of 0.5 ( sd : 1.4 ) , 0.5 ( sd : 1.3 ) , and 0.5 ( sd : 1.2 ) in the placebo , 150 mg/day , and 300 mg/day groups , respectively , were followed for 6 months . RESULTS Adolescents in the 300 mg/day group had a significant reduction in BMI z-score 6 weeks after quitting ( β = -0.16 , CI = ( -0.29 , -0.04 ) , P-value = 0.01 ) . This result was not sustained at the 6-month follow-up . CONCLUSIONS A reduction in BMI z-score during smoking cessation with bupropion has important implication s for the future of adolescent smoking cessation . These results are particularly relevant for adolescents who have either overweight or obesity or who have reservations about quitting for fear of gaining weight or BMI AIMS To compare the efficacy and safety of a novel psychological intervention for smoking cessation called psychodynamic model ( PDM ) training to an active control condition of sustained-release bupropion . DESIGN R and omized controlled clinical trial with allocation concealment . SETTING Private psychiatric practice . PARTICIPANTS Seven hundred and seventy-nine adult smokers recruited by advertising . INTERVENTIONS PDM training ( n = 366 participants ) consisted of a very brief ( 1.5 days ) psychoeducation and a supervised training in autosuggestion techniques ( guided imageries ) aim ed at enhancing self-management , decidedness , assertiveness , security and competence in relationships , natural functions of organs and awareness of bodily functions . Bupropion SR ( n = 413 ) was increased to 150 mg twice daily over 1 week and given over a 8-week period . MEASUREMENTS Twelve-month continuous abstinence confirmed by exhaled carbon monoxide ( CO ) of 9 parts per million ( p.p.m . ) or less at all interviews conducted at 3 , 6 and 12 months . FINDINGS Intention-to-treat analysis revealed Russell st and ard 12-month continuous abstinence rates of 39.1 % in the psychotherapy group versus 12.3 % in the bupropion SR group ( P < 0.001 ) with a relative benefit ( RB ) of 3.16 ( 2.38 - 4.26 ) . Completer analysis revealed 12-month continuous abstinence rates of 39.9 % in the psychotherapy group versus 22.5 % in the bupropion group [ P < 0.001 ; RB 1.78 ( 1.35 - 2.34 ) ] . Of note , bupropion abstinence rates were comparable to previous medications/placebo-only comparisons in geographically different sample s. CONCLUSIONS The 1.5-day psychotherapy exceeded bupropion 's efficacy , presenting an alternative to pharmacological smoking cessation aids , especially for smokers who reject drugs to treat their substance dependence , at a similar cost ( Euro 350 ) as the bupropion treatment ( Euro 355 ) Adolescent smokers ( N = 211 ) were r and omized to 1 of 2 groups : ( a ) nicotine patch plus bupropion SR ( sustained release ; 150 mg per day ) or ( b ) nicotine patch plus placebo . Group skills training sessions were conducted each week by research staff . Abstinence rates at Weeks 10 and 26 were as follows : ( a ) patch plus bupropion , 23 % and 8 % , ( b ) patch plus placebo , 28 % and 7 % . Despite the lack of a treatment effect , a large majority of adolescents in both treatment groups reduced their consumption to a few cigarettes per day or less and maintained this reduction over time . Similarly , an examination of survival curves revealed that by the end of treatment many had managed to avoid a return to daily smoking . These findings are encouraging and suggest new avenues for research . For example , treatments of the kind examined in this report , augmented by extended maintenance therapies , may yield higher long-term success rates OBJECTIVE The administration of antidepressant drugs was shown to positively affect the rate of smoking cessation . This study evaluates the efficacy of nortriptyline in an antismoking program . METHODS A possible r and omized double-blind study that included 144 patients who were r and omized to receive nortriptyline , 75 mg/d ( 68 patients ) , or placebo ( 76 patients ) , during 6 consecutive weeks . All patients attended behavioral group orientation for 5 weeks . The rate of success , complications , adherence to the regime , and factors of pretreatment prognosis were evaluated ( multivariate analysis ) . RESULTS The groups were balanced in relation to the characteristics of the patients on entering the study . Patients receiving nortriptyline showed significantly higher cessation rate ( 55.9 % ) compared to the group receiving placebo ( 23.3 % ; p < 0.001 ) . In a univariate analysis on prognosis factors influencing the rate of cessation in our study , the Fagerström test results ( p = 0.005 ) and nortriptyline ( p < 0.001 ) were identified . Logistic regression showed that a Fagerström test score of < 7 ( odds ratio [ OR ] , 3.1 ; 95 % confidence interval [ CI ] , 1.47 to 6.7 ; p = 0.003 ) and nortriptyline use ( OR , 4.1 ; 95 % CI , 2 to 8.3 ; p < 0.001 ) were independent factors impacting the rate of success for smoking cessation . No significant complications were observed in the nortriptyline group . CONCLUSION This study showed that nortriptyline significantly increases the smoking cessation rate in chronic smokers , as compared to the placebo group , without any significant side effects Objectives : This study evaluated the effectiveness of behavioral interventions ( brief counseling , nonspecific psychological support in groups — NSGS and cognitive behavioral group therapy — CBGT ) in combination with bupropion SR for smoking cessation in the field , through a smoking cessation clinic . Methods : Two-hundred- and -five smokers were enrolled in a 19-week course during 2007/ 2008 , and were r and omly assigned to : bupropion SR combined with brief counseling ( group A ) , bupropion SR combined with NSGS ( group B ) , bupropion SR combined with CBGT ( group C ) , or CBGT as the only approach ( group D ) . Results : Continuous abstinence rates at the end of therapy were 53.2 % for group A , 62.9 % for group B , 50.0 % for group C , and 22.2 % ( p < 0.05 ) for group D. Sustained abstinence rates in 12 months were 29.6 % , 28.1 % , 34.3 % and 19.4 % ( p > 0.05 ) , respectively . Conclusions : Bupropion SR is an effective aid for smoking cessation in clinical practice . NSGT increased the chances for success at the end of therapy when combined with bupropion SR , while CBGT as monotherapy was less effective compared with the approaches including pharmacotherapy . It is suggested that smoking cessation interventions in real-life healthcare setting s should be implemented through comprehensive programs using pharmacotherapy where applicable , combined with NSGT , and integrated by specialized healthcare professionals OBJECTIVE This research examined why smokers receiving combination medication for smoking cessation are more likely to quit smoking than are those who receive either single agent ( monotherapy ) or placebo . METHOD Data were collected from 1,504 current smokers ( 58.2 % women , 83.9 % White ; mean age = 44.67 years , SD = 11.08 ) participating in a cessation clinical trial who were r and omized to 1 of 6 cessation pharmacotherapy conditions ( placebo , nicotine patch , nicotine lozenge , bupropion , nicotine patch + nicotine lozenge , and bupropion + nicotine lozenge ) . Participants completed ecological momentary assessment s 4 times a day , concerning 5 hypothesized mediators ( negative affect , positive affect , craving , smoking expectations , and withdrawal ) of pharmacotherapy effects . Medications were provided for 8 - 12 weeks post-quit along with 6 individual counseling sessions . Mediational paths were estimated via a novel Bayesian approach with estimation of multiple mediator models . RESULTS Biochemically confirmed 8-week abstinence was the outcome variable , with the monotherapy and combination pharmacotherapy composites producing 45 % ( n = 689 ) and 54 % ( n = 478 ) abstinence rates , respectively . The univariate models suggested that the combination treatments produced higher abstinence rates than the monotherapies because of greater suppression of withdrawal , craving , and smoking expectations . However , multiple mediator models showed that the suppression of craving on the quit day produced the strongest mediational effects and could account for the mediational effects of other tested variables . CONCLUSION Suppression of craving on the quit day significantly mediates the clinical effects of monotherapies and combination smoking pharmacotherapies , and the higher abstinence rates for combination therapy versus monotherapies appear primarily due to greater craving suppression BACKGROUND Smoking cessation rates with current therapy are suboptimal . One class of drugs that may improve cessation is the tricyclics . OBJECTIVE To add nortriptyline hydrochloride to a behavioral smoking cessation program to enhance cessation rates and reduce withdrawal symptoms . SUBJECTS AND METHODS We conducted a r and omized , double-blind , placebo-controlled trial at an affiliated Department of Veterans Affairs Medical Center and an Army Medical Center . Subjects were aged 18 through 70 years , smoked 10 or more cigarettes per day , and were without current major depression . Nortriptyline hydrochloride or matched placebo was started at 25 mg before bed 10 days prior to quit day and titrated to 75 mg/d or to the maximal tolerated dose . The behavioral intervention consisted of 2 group sessions and 12 individual follow-up visits . Withdrawal symptoms were measured using a daily diary , and smoking cessation was defined as self-reported abstinence , expired carbon monoxide of 9 ppm or less , and a 6-month urine cotinine level of less than 50 ng/mL. RESULTS A total of 214 patients were r and omized ( 108 to nortriptyline and 106 to placebo ) . There was a significant reduction in several withdrawal symptoms including anxious/tense , anger/irritability , difficulty concentrating , restlessness , and impatience by day 8 after quit day in the nortriptyline group . The cessation rate at 6 months was 15 ( 14 % ) of 108 and 3 ( 3 % ) of 106 , respectively ( P = .003 ; absolute difference , 11 % ; 95 % confidence interval , -18 % to -4 % ) . Nortriptyline caused frequent adverse effects , including dry mouth ( 64 % ) and dysgeusia ( 20 % ) . CONCLUSIONS We conclude that nortriptyline led to an increased short-term cessation rate compared with placebo . In addition , there were significant , but relatively small , reductions in withdrawal symptoms . Nortriptyline may represent a new therapeutic approach to smoking cessation This 6-week , r and omized , open-label pilot study estimated the treatment effect size of gabapentin ( n = 17 ) compared with bupropion SR ( n = 19 ) for smoking cessation , thereby allowing sample size calculations for a definitive comparison study . The primary outcome measure was smoking cessation . Secondary outcome measures included smoking reduction and withdrawal severity . Gabapentin was less efficacious than bupropion for smoking cessation but was associated with fewer dropouts from adverse effects . Withdrawal severity was less with bupropion . Bupropion remains the first-line non-nicotine pharmacotherapy for smoking cessation . Further study is required to determine if gabapentin has any useful role in smoking cessation . Based on our primary outcome measure , 79 subjects would be required in each treatment group of a two-armed study to achieve 90 % power for detecting a difference in efficacy between gabapentin and bupropion This study examined the psychometric properties of an Italian version of the Fagerström Test for Nicotine Dependence in a sample of 593 smokers who were enrolled in a r and omized Phase IV clinical trial to compare bupropion to placebo , This version was administered at baseline , and from each participant an expired air carbon monoxide ( CO ) measure was taken . Spearman correlations between the Total score and CO concentration were .27 in the combined sample and .27 and .25 among men and women , With respect to the internal consistency reliability , the coefficient alpha was low ( alpha = .55 ) in the combined sample and among men ( .59 ) and women ( .50 ) . While the Total score predicted abstinence at 7 wk . , it was not significantly related to continuous abstinence at 12 mo . postr and omization . The properties of the Italian version of the Fagerström Test for Nicotine Dependence appear to be consistent with other versions described in the literature BACKGROUND A past history of major depression or alcoholism has been associated with poorer smoking treatment outcomes . AIM To evaluate the efficacy of bupropion for smoking cessation in smokers with a former history of major depression or alcoholism , and changes in depressive symptoms during smoking abstinence . METHOD Data were drawn from a multicentre trial of bupropion for smoking cessation . Smokers ( n = 615 ) received placebo or bupropion sustained-release at 100 , 150 , or 300 mg/day for six weeks after target quit date ( TQD ) . The primary outcome was the point prevalence smoking abstinence at the end of treatment and at one year . The Beck Depression Inventory ( BDI ) was used to assess depressive symptoms . RESULTS A significant dose-response effect of bupropion for smoking cessation was found . This was independent of history of major depression or alcoholism . Among those continuously abstinent from smoking for two weeks following TQD , an increase in BDI score was associated with a return to smoking at end of treatment . CONCLUSIONS Bupropion is efficacious for smoking cessation independently of a former history of major depression or alcoholism . Increases in depressive symptoms during an initial period of abstinence are associated with a return to smoking This is the first study to examine the prevalence and effects of major depression ( MDD ) in a sample of adolescent smokers ( N = 211 ) undergoing treatment for nicotine dependence . We assessed MDD at baseline and end of treatment with the mood disorders portion of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders , fourth edition ( DSM-IV ) . Eleven percent of participants reported a history of MDD ( 6 % of males and 21 % of females ) . Study variables did not distinguish those with and without a history of MDD . End of treatment abstinence rates and relapse rates were similar in both groups . Two participants ( 1 % ) , both female , experienced onset of MDD during the treatment . The findings provide further evidence that MDD is a comparatively common disorder among children and adolescents and that clinicians should monitor and be prepared to respond to depression that may emerge during the treatment of nicotine-dependent adolescents INTRODUCTION St. John 's wort ( SJW ) is a widely used herbal supplement . The predominant mechanism(s ) accounting for the activity of SJW in vivo are , however , unclear . The purpose of this study was to investigate the efficacy of SJW for smoking cessation . METHODS We conducted a r and omized , blinded , placebo-controlled , three-arm , dose-ranging clinical trial . A total of 118 subjects were r and omly allocated to receive SJW 300 mg , 600 mg , or a matching placebo tablet 3 times a day combined with a behavioral intervention for 12 weeks . Self-reported smoking abstinence was biochemically confirmed with expired air carbon monoxide . RESULTS Mean age of the study participants was 37.6 + /- 12.4 years ; they smoked an average of 20.0 + /- 6.6 cigarettes per day for 20 + /- 12.1 years . The study dropout rate was high ( 43 % ) . By intention-to-treat analysis , no significant differences were observed in abstinence rates at 12 and 24 weeks between SJW dose groups and placebo . SJW did not attenuate withdrawal symptoms among abstinent subjects . Abstinence rates did not differ by study group among subjects who took at least 75 % of their study medication . No significant side-effects were noted with SJW . CONCLUSIONS In this r and omized trial , SJW did not increase smoking abstinence rates . Our data , in combination with data from other studies , suggest that SJW has little role in the treatment of tobacco dependence BACKGROUND Current guidelines recommend smoking cessation and weight management for secondary prevention in patients post-myocardial infa rct ion . However , little is known about the effects of smoking cessation on weight change post-myocardial infa rct ion . METHODS We examined patterns of weight change and its effects on blood pressure and glycemic control using data from a r and omized trial investigating the effect of bupropion on smoking cessation in patients post-myocardial infa rct ion . Weight change was compared among 3 groups of patients : those who were completely abstinent ( n = 92 ) , those who smoked intermittently ( n = 49 ) , and those who smoked persistently ( n = 38 ) during the 12-month follow-up . Analyses were restricted to patients who attended all follow-up visits . RESULTS The median weight at baseline was 77.1 kg ( interquartile range [ IQR ] , 66.0 , 87.5 ) , and 64.3 % of patients were overweight/obese ( body mass index ≥25.0 kg/m(2 ) ) . The median weight gain at 12 months was 4.0 kg ( IQR , 0 - 7.0 ) , with more than one third gaining > 5 kg . The proportion of patients who were overweight/obese increased by approximately 10 % , and 23.2 % of patients moved up a body mass index category . Abstainers gained a median of 4.8 kg ( IQR , 1.0 , 8.6 ) , intermittent smokers gained a median of 2.0 kg ( IQR , -2.0 , 5.0 ) , and persistent smokers gained a median of 3.0 kg ( IQR , -0.8 , 6.0 ) . Weight gain was associated with an increase in blood pressure and requirements for hypoglycemic medications at 12 months . CONCLUSIONS The majority of patients attempting to quit smoking gain weight 12 months post-myocardial infa rct ion , with abstainers gaining more weight than those who return to smoking . Weight gain was associated with an increased prevalence of hypertension and diabetes BACKGROUND Cigarette smoking causes reduced health-related quality of life ( QoL ) and smoking abstinence improves health-related QoL. We assessed the effects of treatment for tobacco dependence on the health-related QoL in a 52-week r and omized controlled trial of varenicline and bupropion sustained release ( SR ) . METHODS Subjects who smoked ≥10 cigarettes per day for the past year were r and omly assigned to receive varenicline 1 mg twice daily ( n = 696 ) , bupropion SR 150 mg twice daily ( n = 671 ) or placebo ( n = 685 ) for 12 weeks and followed post-therapy for an additional 40 weeks . Health-related QoL was assessed using the Smoking Cessation Quality of Life question naire at baseline and Weeks 12 , 24 and 52 . RESULTS Health transition ( perceived health compared with baseline ) and self-control were both significantly improved among subjects receiving varenicline and bupropion SR compared with placebo at Weeks 12 , 24 and 52 . Similarly , varenicline-treated subjects had significantly improved health transition and self-control compared with subjects who received bupropion SR at Weeks 12 and 24 , and at Week 52 for health transition . A significant positive association existed between length of continuous abstinence and improved health transition , vitality , self-control , anxiety and overall mental profile . In most instances both a direct and an indirect effect ( through continuous smoking abstinence ) of each active treatment ( vs. placebo ) contributed to improved self-control and health transition . CONCLUSION Treatment with varenicline and bupropion SR for smoking cessation result ed in improved self-control and health transition that was mediated in large part by continuous smoking abstinence & NA ; A total of 104 men who were heavy smokers ( minimum of a pack , and averaging 35 cigarettes a day ) participated in a 10‐week program to break the habit . The majority ( N=83 ) received group therapy , and the remainder were seen individually . Each S was r and omly assigned to one of the following drug conditions : no pills , placebo , lobeline , dextroamphetamine and imipramine . Pretesting established each S as a good ( N=67 ) or poor ( N=37 ) risk to stop smoking . Results indicated that , both at the end of treatment and at followup 3 months later , group was superior to individual therapy , treatment without drugs was more effective than taking medication ( especially for high risk cases ) , and low‐risk did better than high‐risk Ss . Successful Ss stayed in treatment longer than did failures . Relapse was associated with life situations of loneliness , passivity , boredom , tension and personal tragedy . The best predictor of resistance to relapse was the abrupt and complete breaking of the habit during the first 2 weeks of the program ( " cold turkey " ) OBJECTIVE The study examined the efficacy , tolerability , and safety of supportive group psychotherapy and adjunctive sustained-release bupropion for nicotine addiction in patients with schizophrenia . METHOD Eight patients participated in a 14-week open-label trial . End expired breath carbon monoxide level , symptom levels , neuropsychological performance , and suppression of the P50 event-related potential were measured before and after the 14-week trial . RESULTS Patients showed a decrease in carbon monoxide levels that was not associated with any worsening in symptom , neuropsychological , or P50 suppression measures . CONCLUSIONS Use of sustained-release bupropion in combination with supportive group therapy may help patients with schizophrenia decrease their cigarette consumption There is a significant need for evidence -based treatments for adolescent smoking cessation . Prior research , although limited , has suggested potential roles for bupropion sustained-release ( SR ) and contingency management ( CM ) , but no previous studies have assessed their combined effect . In a double-blind , placebo-controlled design , 134 adolescent smokers were r and omized to receive a 6-week course of bupropion SR + CM , bupropion SR + non-CM , placebo + CM , or placebo + non-CM , with final follow-up at 12 weeks . The primary outcome was 7-day cotinine-verified point prevalence abstinence , allowing for a 2-week grace period . Combined bupropion SR + CM treatment yielded significantly superior abstinence rates during active treatment when compared with placebo + non-CM treatment . In addition , combined treatment showed greater efficacy at multiple time points than did either bupropion SR + non-CM or placebo + CM treatment . Combined bupropion SR and CM appears efficacious , at least in the short-term , for adolescent smoking cessation and may be superior to either intervention alone INTRODUCTION Detailed analysis of adherence to tobacco cessation medications and predictors of adherence is sparse in published literature . In this analysis , we assessed adherence to tobacco dependence treatment , association of adherence with abstinence , and predictors of adherence . METHODS We analyzed pooled results from 2 r and omized controlled trials . Adult smokers ( N = 2,045 ) who were r and omly assigned to 12 weeks of treatment and took at least 1 dose of the assigned medication ( varenicline [ 692 ] , bupropion sustained release [ 669 ] , or placebo [ 684 ] ) were included . Treatment adherence was defined as any subject who took > or=1 dose of study drug for > or=80 % days during the 12-week treatment period ( " completers " ) . Smoking abstinence was assessed using carbon monoxide-confirmed 4-week continuous abstinence rate at end of treatment ( Weeks 9 - 12 ) . RESULTS Adherence rates for completers who received varenicline , bupropion , and placebo groups , respectively , were 99.3 % , 98.8 % , and 99.2 % . There was a positive correlation between adherence to treatment and tobacco abstinence in all treatment groups . Treatment effect sizes ( odds ratios ) for active therapy compared with placebo were similar whether considering all subjects or only the completer subset . Age , cigarettes per day , and Week-2 abstinence were significant predictors of adherence for all treatment groups ( all p < .05 ) , with Week-2 abstinence the strongest predictor . DISCUSSION Adherence to pharmacotherapy for smoking cessation is highly correlated with improved tobacco abstinence . Early abstinence experience is a strong driver of adherence Various theories have proposed mechanisms for drug motivation and relapse . For instance , negative reinforcement theories focus on the alleviation of withdrawal . However , other theories and some data cast doubt on the importance of withdrawal as a motivator of addictive drug use . Using data from a r and omized double-blind placebo-controlled smoking cessation treatment study ( N=608 ) , this research examined the impact of withdrawal on drug motivation and the ability to maintain abstinence . Withdrawal was experimentally manipulated by r and omly assigning participants to receive active bupropion versus placebo . Mediation analyses revealed that active bupropion reduced the amount of withdrawal and craving that individuals reported in the 1st week post quit ; modest support was also found for smaller declines in positive affect . These effects , in turn , were all positively associated with posttreatment abstinence . These results implicate withdrawal as an important factor in motivating persistent tobacco use Smoking is a risk factor for complications during and after surgery , but most smokers are unable to quit before elective surgery . We tested the efficacy of bupropion in improving smoking cessation rates in this setting by enrolling 47 patients from the elective surgery waiting list in a double‐blind r and omised controlled trial . Patients receiving bupropion had a lower daily cigarette consumption at the time of hospital admission , median ( IQR ) cigarettes per day : 6 ( 2–7 ) vs. 15 ( 9–20 ) , p = 0.046 . They also had a reduction in end‐expired carbon monoxide ( p = 0.004 ) , a known contaminant of cigarette smoke , and increased arterial oxygen saturation on pulse oximetry ( p = 0.011 ) . They were more likely to have stopped smoking at the 3‐week visit ( p = 0.036 ) , but not at the 6‐week visit ( p = 0.25 ) or at the time of hospital admission for surgery ( p > 0.99 ) . This study found that smokers waiting for elective surgery are more likely to reduce or stop smoking when treated with bupropion AIMS The primary aim of this study was to compare the efficacy of smoking cessation treatment using a combination of nicotine patch and bupropion vs. nicotine patch and placebo bupropion . A secondary aim was to investigate whether the efficacy of bupropion is moderated by belief about whether one is receiving active or placebo medication . METHODS Participants were recruited from a residential substance abuse treatment program and the community . We r and omly assigned 148 smokers with between 2 and 12 months of alcohol abstinence to nicotine patch plus bupropion or nicotine patch plus placebo . All participants also received seven counseling sessions . RESULTS At follow up , differences between medication conditions were not significant . Seven-day point prevalence quit rates in the patch plus bupropion vs. patch plus placebo conditions at week 24 were 6 % and 11 % , respectively . Differences between groups on prolonged abstinence and time to first smoking lapse were also not significant . However , among participants who received bupropion , those who accurately " guessed " that they were receiving bupropion were more likely to remain abstinent than those who incorrectly believed they were receiving placebo . CONCLUSIONS Findings do not support combining nicotine patch and bupropion for smoking cessation in this population . However , findings support previous studies suggesting the importance of assessing the blind in smoking cessation studies and its possible moderating effect on medication efficacy . Future directions for enhancing smoking cessation outcome in these smokers include investigations of intensive behavioral and pharmacological interventions , including studies of potential interactions between individual genetic differences and medication efficacy AIMS We investigated whether variants in the serotonin transporter gene ( SLC6A4 ) influence smoking cessation rates using antidepressant therapy ( i.e. bupropion and nortriptyline ) . DESIGN Pharmacogenetic ( secondary ) analysis of a r and omized , placebo-controlled efficacy trial of bupropion and nortriptyline for smoking cessation . SETTING Single-centre study , Maastricht University , the Netherl and s. PARTICIPANTS A total of 214 of 255 ( 84 % ) current daily smokers participating in a r and omized controlled efficacy trial . MEASUREMENTS Subjects were genotyped for three functional variants in SLC6A4 ( 5-HTTLPR , STin2 , rs25531 ) . Primary outcome measures were prolonged abstinence from weeks 4 - 12 , 4 - 26 and 4 - 52 . Secondary outcome measures included 7-day point prevalence abstinence at weeks 4 , 12 , 26 and 52 . FINDINGS Carriers of the 5-HTTLPR high-activity L-variant had higher prolonged cessation rates with bupropion than placebo [ odds ratio ( OR ) = 1.44 , 95 % confidence interval ( CI ) = 1.01 - 2.05 , P = 0.04 ] . Combining the three variants result ed in increased prolonged cessation rates for both bupropion and nortriptyline among carriers of four to five high-activity variants ( bupropion : OR = 2.00 , 95 % CI = 1.21 - 3.29 , P = 0.01 ; nortriptyline : OR = 1.91 , 95 % CI = 1.02 - 3.56 , P = 0.04 ) . Similar results were found for point prevalence abstinence . CONCLUSIONS Bupropion and nortriptyline seem to be more effective in smoking cessation among SLC6A4 high-activity variant carriers , probably by blocking the increased serotonin transporter activity , thereby increasing serotonin levels . Prospect i ve studies have to assess if this can improve cessation rates when treatment is targeted at individuals based on their genotypes We examined whether a pretreatment phenotypic marker of nicotine metabolism rate ( NMR ) predicts successful smoking cessation with bupropion . Smokers ( N = 414 ) were tested for pretreatment NMR , based on the ratio of 3′‐hydroxycotinine/cotinine derived during smoking , before entering a placebo‐controlled r and omized trial of bupropion plus counseling . At the end of the 10‐week treatment phase , slow metabolizers ( 1st NMR quartile ) had equivalent quit rates with placebo or bupropion ( 32 % ) . Fast metabolizers ( 4th NMR quartile ) had low quit rates with placebo ( 10 % ) , and these were enhanced significantly by bupropion ( 34 % ) . Smokers in the 2nd quartile ( placebo : 25 % , bupropion : 30 % ) and the 3rd quartile ( placebo : 20 % , bupropion : 30 % ) did not benefit significantly from bupropion . At the 6‐month follow‐up , the relationship between the NMR and quitting remained similar , but was no longer statistically significant . A pretreatment assessment of NMR may identify smokers who are most and least likely to benefit from treatment with bupropion for smoking cessation OBJECTIVE To compare the combination of a nicotine inhaler and bupropion to either treatment alone for initiating smoking abstinence and relapse prevention . METHODS Smokers were r and omized to receive a nicotine inhaler , bupropion , or both for 3 months . At 3 months , smoking-abstinent study participants were r and omized to their initial medications or placebo . Participants who were smoking at 3 months were r and omized to an alternative treatment regimen or placebo . This study was conducted from July 2001 to January 2003 . RESULTS A total of 1700 smokers were r and omized to treatment ( phase 1 ) for 3 months . Among the 941 study participants eligible for r and omization to the phase 2 trial , 837 continued in the study . For the phase 2 trial , 405 smoking-abstinent participants were r and omized to relapse prevention for 9 additional months , and 432 smokers were r and omized to re-treatment for an additional 3 months . At the end of the initial 3 months of treatment ( phase 1 ) , 82 ( 14 % ) of 566 , 145 ( 26 % ) of 567 , and 194 ( 34 % ) of 567 study participants receiving a nicotine inhaler , bupropion , or both , respectively , were abstinent from smoking . Of the 405 smoking-abstinent participants at the end of 3 months , the bupropion group had more smokers than the placebo group ( mean No. of smokers , 1.5 vs 1.1 ; P < .001 ) , and the nicotine inhaler group had higher smoking abstinence rates at 12 months than the placebo group . Those receiving combination therapy had reduced rates of relapse to smoking for the first 3 months of relapse prevention , but this difference disappeared after the initial 3 months . Of the 432 study participants who were smoking at the end of 3 months and who received an alternative treatment regimen , the 223 smokers initially assigned to a nicotine inhaler were more likely to stop smoking at 6 months if they were re-treated with bupropion instead of placebo ( 8 [ 7 % ] of 111 vs 0 [ 0 % ] of 112 ; P = .003 ) , and the 209 smokers initially treated with bupropion and re-treated with a nicotine inhaler did not have significantly higher smoking abstinence rates ( 6 [ 6 % ] of 104 vs 3 [ 3 % ] of 105 ; P = -.50 ) . CONCLUSION Combined therapy with a nicotine inhaler and bupropion increased smoking abstinence rates . Continuation of the initial combination therapy does not appear to prevent relapse to smoking . Timing of re-treatment and alternative approaches to relapse prevention should be further examined In a double-blind study , 15 cigarette smokers self-monitored 10 withdrawal symptoms . For the first 21 days ( baseline ) , subjects received doxepin hydrochloride , up to 150 mg/day , or inert medication while continuing to smoke . On day 22 , they were instructed to stop smoking ; medication was continued . Withdrawal symptoms on the first 28 days of treatment ( baseline and 7 days of attempted cessation ) were analyzed . During cessation , subjects taking doxepin reported significantly less craving for cigarettes . Results from this study and others suggest that antidepressants may attenuate the severity of symptoms during withdrawal from addictive substances STUDY OBJECTIVE To assess the efficacy and safety of long-term bupropion therapy for nicotine dependence in adolescents . DESIGN Prospect i ve , double-blind , placebo-controlled trial . SETTING Outpatient clinic in Innsbruck , Austria . SUBJECTS Twenty-two adolescents , aged 16 - 19 years , with nicotine dependence . INTERVENTION Participants were r and omly assigned to receive bupropion 150 mg/day or placebo for 90 days . MEASUREMENTS AND MAIN RESULTS Patients were classified as abstinent or relapsed on day 0 ( when study drug was started ) and again on days 30 and 90 , according to their self-reports . Treatment failure was defined as relapse or nonattendance . Time to first treatment failure was the primary outcome measure . Mean cumulative abstinence duration was significantly greater in the bupropion group than in the placebo group ( 78.4 + /- 39.6 vs 30.2 + /- 19.2 days . p=0.0042 ) . CONCLUSION Bupropion seems to be an effective and well-tolerated pharmacologic adjunct to psychosocial and behavioral treatment programs for some adolescent nicotine-dependent patients . However , experienced clinicians should continuously monitor patients for adverse effects Treatment trials involving smoking in alcoholics with major depression are scarce , despite the common co-occurrence of these disorders . In this study , 25 smokers with DSM-III-R diagnoses of both major depressive disorder and alcohol dependence were r and omized to fluoxetine or placebo in a 12-week , double-blind , parallel group trial . Almost half ( 48 % ) of the patients had made a suicide attempt in the week before hospitalization ( where recruitment was performed ) , and 84 percent reported suicidal ideations during that week . Those in the fluoxetine group demonstrated a significant within-group decrease in smoking during the course of the study , whereas those in the placebo group did not . Those in the fluoxetine group smoked 27 percent fewer cigarettes than those in the placebo group , although this difference was not statistically significant . Cumulative alcohol consumption during the 12 weeks of the pharmacotherapy trial was four times as high in the placebo group as in the fluoxetine group , though this difference was not statistically significant in this limited-sized sample . The change in smoking was significantly associated with a change in drinking . These preliminary findings suggest that fluoxetine has the potential for treating the smoking and drinking behaviors of depressed alcoholic smokers BACKGROUND CYP2B6 is the primary enzyme involved in bupropion ( Zyban ; GlaxoSmithKline , Research Triangle Park , North Carolina ) metabolism . Genetic polymorphisms in CYP2B6 , such as CYP2B6 * 6 , can alter bupropion metabolism and may affect bupropion treatment outcome . METHODS Subjects participated in a smoking cessation clinical trial of bupropion versus placebo . The main outcome was a 7-day point prevalence abstinence rate measured 10 weeks after the start of treatment ( i.e. , end of treatment ) and at the 6-month follow-up ; secondary outcomes were severity of adverse effects , withdrawal , and urge to smoke . Subjects were haplotyped for the CYP2B6 * 6 variants . RESULTS Among smokers in the CYP2B6 * 6 group ( CYP2B6 * 1/*6 or CYP2B6 * 6/*6 genotype , n = 147 , 45 % of the population ) , bupropion produced significantly higher abstinence rates than placebo at the end of treatment ( 32.5 % vs. 14.3 % , p = .01 ) and at the 6-month follow-up ( 31.2 % vs. 12.9 % , p = .008 ) . In contrast , bupropion was no more effective than placebo for smokers in the CYP2B6 * 1 group ( CYP2B6 * 1/*1 , n = 179 ) at the end of treatment ( 31.0 % vs. 31.6 % , p = .93 ) or at the 6-month follow-up ( 22.0 % vs. 21.5 % , p = .94 ) . There was a significant genotype by treatment interaction at the end of treatment ( odds ratio [ OR ] = 2.97 , confidence interval [ CI ] = 1.05 - 8.40 , p = .04 ) , which was similar at 6-month follow-up ( OR = 2.98 , CI = .98 - 9.06 , p = .05 ) . CONCLUSIONS These data suggest that smokers with the CYP2B6 * 6 genotype have a higher liability to relapse on placebo and that they may be good c and i date s for bupropion treatment for smoking cessation OBJECTIVES To compare the effect of oral selegiline plus nicotine patch with placebo plus nicotine patch on smoking cessation rates . DESIGN R and omized double-blind placebo-controlled trial . SETTING Three community-based clinics . PARTICIPANTS One hundred and nine male and female smokers aged 18 - 55 years , who smoked at least 15 cigarettes/day . INTERVENTIONS Oral selegiline , 2.5 mg , or placebo twice/day initiated 1 week before the quit day , followed by 5 mg oral selegiline or placebo twice daily for 26 weeks , plus active nicotine skin patch to all participants for the first 8 weeks only . Measures of continuous abstinence rates up to 52 weeks , withdrawal symptoms , blood pressure and adverse events incidence . FINDINGS Twenty-five per cent ( 14 of 56 ) were continuously abstinent for 52 weeks in the selegiline plus nicotine group compared with 11 % ( 6 of 53 ) in the placebo plus nicotine group ( P = 0.08 ) . Craving for cigarettes was lower in the selegiline plus nicotine group 4 weeks after quit day ( P = 0.02 ) . CONCLUSIONS Adding selegiline to nicotine patch was associated with a doubling of the 52-week continuous abstinence rate , but this difference was not statistically significant . Selegiline significantly reduced craving for cigarettes and appeared to mitigate the need for nicotine replacement therapy . The results suggest that selegiline is a promising drug for future smoking cessation research BACKGROUND Bupropion sustained release ( bupropion SR ) has been shown to increase smoking cessation success rates in the US studies . OBJECTIVE To determine whether bupropion SR , in combination with counselling , is effective for smoking cessation in a multi-country study . METHODS This r and omized , double-blind , placebo-controlled trial enrolled 707 smokers . A total of 527 received bupropion SR 300 mg daily for 7 weeks and 180 received placebo . A total of 11 clinic visits and 10 telephone contacts were scheduled , during the course of 1 year . Seven-week and 12-month abstinence rates were the study outcomes . RESULTS Both continuous and weekly point prevalence smoking abstinence rates were significantly higher in the bupropion SR group compared with placebo . The continuous abstinence rate from weeks 4 to 7 was 46 % in the bupropion SR group compared with 23 % in the placebo group [ odds ratio ( OR ) = 2.82 ; 95 % confidence interval ( CI ) 1.89 - 4.28 ; P < 0.001 ) . At month 12 , the continuous abstinence rates were 21 % for the bupropion SR group and 11 % for the placebo group ( OR = 2.19 ; 95 % CI 1.29 - 3.86 , P = 0.002 ) . For most nicotine-withdrawal symptoms small changes were measured . Adverse events were higher for the bupropion SR group compared with placebo ( insomnia 24 % vs. 15 % ; dry mouth 13 % vs. 5 % ) . CONCLUSION Bupropion SR in combination with counselling increased the abstinence rate compared with placebo , and was well tolerated Smokers ( N = 224 ) were r and omized to 1 of 3 groups : ( a ) transdermal system ( TNS ) + placebo ; ( b ) TNS + paroxetine ( 20 mg ) ; ( c ) TNS + paroxetine ( 40 mg ) . Assignment to treatment was double-blind . Nicotine patch ( TNS ) treatment was provided for 8 weeks ; paroxetine or placebo was provided for 9 weeks . Abstinence rates at Weeks 4 , 10 , and 26 were as follows : ( a ) TNS + placebo : 45 % , 36 % , and 25 % ; ( b ) TNS + paroxetine ( 20 mg ) : 48 % , 33 % , and 21 % ; ( c ) TNS + paroxetine ( 40 mg ) : 57 % , 39 % , and 27 % . The differences were not statistically significant . The combined treatment was more effective in reducing both craving and depression symptoms associated with smoking cessation . A subgroup analysis comparing compliant participants was also conducted . Abstinence rates at Weeks 4 , 10 , and 26 were as follows : ( a ) TNS + placebo : 46 % , 35 % , and 24 % ; ( b ) TNS + paroxetine ( 20 mg ) : 64 % , 43 % , and 33 % ; ( c ) TNS + paroxetine ( 40 mg ) : 74 % , 51 % , and 38 % . The differences between paroxetine groups and placebo at Week 4 were statistically significant . Although paroxetine may add value to the current st and ard of care in excess of potential risk , more conclusive evidence is needed The clinical pharmacology of biochemical measures of nicotine exposure has been thoroughly review ed with regard to usefulness and limitations in detecting abstinence from cigarette smoking . While plasma nicotine concentration measures only acute nicotine exposure , plasma , salivary , and urine cotinine concentrations reflect exposure over an extended period of time . Although , expired carbon monoxide ( CO ) is frequently used to confirm self reports , it has a relatively short half life , calling into question whether this measure might provide misleading information by exaggerating smoking cessation success rates . To examine this question , we analyzed expired CO , plasma cotinine and self report data collected in a clinical trial in which subjects ( N=207 ) were r and omly assigned to gain- or loss-framed messages for smoking cessation in combination with open label sustained-release bupropion ( 300 mg/day ) . In examining measurements collected at 6 weeks , 3 and 6 months , results showed that CO significantly overestimated abstinence rates as compared with cotinine , although the discrepancy was less at the later time points . These data suggest that while expired CO is a useful and well-established marker in certain context s , when testing extended abstinence from smoking with non-nicotine medications , cotinine measurements should be preferred The influence of depressive symptoms on smoking cessation was examined among 600 African American smokers who participated in a r and omized , placebo-controlled trial of sustained-release bupropion hydrochloride . Depressive symptoms were assessed at baseline , at week 6 ( end of treatment ) , and at 6-month follow-up . The study examined three separate questions : ( a ) Whether depressive symptom levels were related to smoking cessation , ( b ) whether bupropion was more effective for smokers who had higher depressive symptoms at baseline ( i.e. , a moderator model ) , and ( c ) whether changes in depressive symptoms would account for the efficacy of bupropion for smoking cessation ( i.e. , a mediator model ) . Depressive symptoms at baseline were not predictive of cessation ; however , increases in depressive symptoms from baseline predicted reduced cessation at the end of treatment , and higher depressive symptoms at week 6 and month 6 were associated with a reduced likelihood of smoking cessation at those time points . The moderator model was not supported , but the mediation analyses indicated that alleviation of depressive symptoms partly accounted for bupropion-assisted smoking cessation at end of treatment . Results extend prior findings to African American smokers and suggest that clinicians consider increases in depressive symptoms after quitting rather than baseline depressive symptoms in predicting risk of treatment failure . Results also suggest that even though bupropion may facilitate cessation in part by reducing depressive symptoms , it appears to be no more effective for more depressed smokers , and that mechanisms other than depressive symptom alleviation account for most of its efficacy OBJECTIVE Bupropion was developed for the treatment of depression , but subsequently was found to be effective for smoking cessation . To date , there are no prospect i ve comparative studies examining its safety in pregnancy . The primary objective was to determine whether bupropion increases the risks for major malformations above baseline . The secondary objective was to examine the rates of live births , stillbirths , spontaneous and therapeutic abortions , mean birth weight , and gestational age at birth . STUDY DESIGN Women who were pregnant or planning a pregnancy and taking bupropion were enrolled in the study . Follow-up of pregnancy outcome was carried out between 4 months and 1 year after delivery . Three comparisons were carried out : 1 ) women exposed to bupropion vs a nonteratogen group ; 2 ) those taking for depression vs other antidepressants , vs a nonteratogen group ; 3 ) spontaneous abortions were compared between those taking for depression , vs another antidepressant group vs a nonteratogen group . RESULTS We completed follow-up on 136 women exposed to bupropion during the first trimester of pregnancy . There were ( 105 ) live births , no major malformations , the mean birth weight was ( 3450 g ) , the mean gestational age at delivery was ( 40 weeks ) , the number of spontaneous abortions was 20 , there were 10 therapeutic abortions , there was 1 stillbirth , and 1 neonatal death . There were no statistically significant differences between any of the end points we examined between the exposed and comparison groups , with the exception of significantly more spontaneous abortions in the bupropion group ( P = .009 ) . CONCLUSION These results suggest that bupropion does not increase the rates of major malformation above baseline . The higher rates of spontaneous abortions are similar to other studies examining the safety of antidepressants during pregnancy OBJECTIVE To examine previous use of nicotine replacement therapy ( NRT ) on the smoking-cessation efficacy of bupropion sustained release ( SR ) . METHODS Secondary analysis of a parallel-group , r and omized , double-blind , placebo-controlled study . Smokers who had , based on self-report , no previous history of NRT ( N = 453 ) or who had used NRT at least once ( N = 440 ) were r and omized to receive placebo , bupropion SR , nicotine transdermal system ( NTS ) , or a combination of bupropion SR and NTS . RESULTS Bupropion SR showed similar efficacy in participants with or without previous use of NRT . CONCLUSION Bupropion SR is effective in promoting smoking abstinence regardless of prior NRT use The authors evaluated the efficacy of fluoxetine hydrochloride ( Prozac ; Eli Lilly and Company , Indianapolis , IN ) as an adjunct to behavioral treatment for smoking cessation . Sixteen sites r and omized 989 smokers to 3 dose conditions : 10 weeks of placebo , 30 mg , or 60 mg fluoxetine per day . Smokers received 9 sessions of individualized cognitive-behavioral therapy , and biologically verified 7-day self-reported abstinence follow-ups were conducted at 1 , 3 , and 6 months posttreatment . Analyses assuming missing data counted as smoking observed no treatment difference in outcomes . Pattern-mixture analysis that estimates treatment effects in the presence of missing data observed enhanced quit rates associated with both the 60-mg and 30-mg doses . Results support a modest , short-term effect of fluoxetine on smoking cessation and consideration of alternative models for h and ling missing data BACKGROUND Tobacco smoking is associated with chronic obstructive pulmonary disease ( COPD ) in more than 80 % of cases . Our aim was to investigate the effect of sustained-release bupropion ( amfebutamone ) ( SR ) in promoting abstinence from smoking in patients with COPD . METHODS In a double-blind , r and omised , placebo-controlled trial 404 individuals with mild or moderate COPD who smoked 15 or more cigarettes per day , were assigned bupropion SR ( 150 mg twice daily ) or placebo for 12 weeks . All patients received smoking cessation counselling . Study medication was taken for 1 week before patients attempted to stop smoking . The primary efficacy endpoint was the complete and continuous abstinence from smoking from the beginning of week 4 to the end of week 7 . Participants were followed up at month 6 . Analysis was by intention to treat . FINDINGS All patients were chronic smokers with a smoking history of about 51 pack-years . Continuous smoking abstinence rates from week 4 to 7 were significantly higher in participants receiving bupropion SR than in those receiving placebo ( 28 % [ 57/204 ] vs 16 % [ 32/200 ] , p=0.003 ) . Continuous abstinence rates from weeks 4 to 12 ( 18 % [ 36/204 ] vs 10 % [ 20/200 ] ) and weeks 4 to 26 ( 16 % [ 32/204 ] vs 9 % [ 18/200 ] ) were also higher in participants receiving bupropion SR than in those taking placebo ( p<0.05 ) . Furthermore , symptoms of tobacco craving and withdrawal were attenuated in those receiving bupropion SR . Seven individuals discontinued study medication because of adverse events . INTERPRETATION Bupropion SRis a well-tolerated and effective aid to smoking cessation in people with mild to moderate COPD OBJECTIVES S-Adenosyl-L-methionine ( SAMe ) is a dietary supplement commonly used to treat depression . SAMe facilitates dopamine and norepinephrine synthesis in the central nervous system . This study investigated the efficacy of SAMe for increasing tobacco abstinence among cigarette smokers . DESIGN A r and omized , blinded , placebo-controlled , three-arm , dose-ranging clinical trial was conducted . Subjects were r and omly allocated to receive SAMe 1600 mg or 800 mg by mouth every day or a matching placebo for 8 weeks . All subjects received a behavioral smoking cessation intervention . Self-reported smoking abstinence was biochemically confirmed with exhaled-air carbon monoxide . SUBJECTS Subjects in the study comprised 120 adults . RESULTS One hundred and twenty ( 120 ) subjects with a mean age of 40.0±14.0 ( SD ) years were enrolled . Participants smoked an average of 19.6±8.6 cigarettes per day for 21±13.2 years . The study dropout rate was high ( 42.5 % ) . By intention-to-treat analysis , no significant differences were observed in abstinence rates at 8 and 24 weeks between SAMe dose groups and placebo . SAMe did not attenuate withdrawal symptoms among abstinent subjects . Rates of gastrointestinal side-effects were higher with SAMe 1600 mg/d compared to placebo . CONCLUSIONS SAMe did not increase smoking abstinence rates . Abstinence and tobacco withdrawal data from this clinical trial suggest that SAMe holds little promise for the treatment of tobacco dependence BACKGROUND Smoking menthol cigarettes is more prevalent among African Americans ( AA ) compared to Whites . Menthol has been found to be inversely related to smoking cessation among AA , yet little is known about the factors associated with menthol smoking among AA light smokers . This study examines baseline demographic , psychological , and smoking factors associated with smoking menthol cigarettes among AA light smokers ( ≤10 cigarettes per day ) . METHODS Participants ( n=540 ) were enrolled in a double blind , placebo-controlled r and omized trial of bupropion in combination with health education counseling for smoking cessation . Bivariate differences between menthol and non-menthol smokers were explored and baseline factors associated with smoking menthol cigarettes were identified . RESULTS Participants averaged 46.5 years in age , predominantly female ( 66.1 % ) , and smoked an average of 8.0 cpd ( SD=2.5 ) . The majority ( 83.7 % ) smoked menthol cigarettes . In bivariate analysis , menthol cigarette smokers were younger ( mean age : 45 vs. 52 years p<0.0001 ) , were more likely to be female ( 68 % vs. 52 % p=0.003 ) and had smoked for shorter duration ( 28 vs. 34 years p<0.0001 ) compared to non-menthol smokers . While depression and withdrawal scores were slightly higher and exhaled carbon monoxide values were lower among menthol smokers , the differences were not statistically significant . CONCLUSIONS Among AA light smokers , younger individuals and females were more likely to smoke menthol cigarettes and may be more susceptible to the health effects of smoking . Appropriately targeted health education campaigns are needed to prevent smoking uptake in this high-risk population Background : Cigarette smoking remains the single largest cause of premature death in the United Kingdom . As part of the government ’s national service framework for coronary heart disease , smoking cessation forms a key part of the strategy . Objectives : To determine the effectiveness of bupropion treatment for smoking cessation in a general practice setting , measuring continuous abstinence from smoking , from 8 weeks to 52 weeks . Design : Prospect i ve observational study . Setting : One general practice ( six whole time equivalent doctors , 11 070 patients ) in rural Northumberl and . Subjects : Of the 243 patients who presented to the practice over a one year period for smoking cessation , a total of 227 motivated people , who were appropriate for bupropion treatment as a pharmacological aid for smoking cessation , entered the study . Continuous smoking cessation at one year was vali date d by an exhaled carbon monoxide level of 10 ppm or less . Results : Fifty patients successfully gave up smoking , giving a one year smoking cessation prevalence with bupropion of 22 % ( 95 % confidence intervals ( CI ) 17 % to 28 % ) . There was no difference in success rate for sex , number of cigarettes smoked , the number of years smoking , or whether there were other smokers in the household or not . Conclusion : Bupropion treatment in this general practice helped 22 % of motivated people to quit and remain stopped smoking at one year . Mainly nurses , whose prescribing rights are restricted and currently exclude bupropion , deliver smoking cessation services in primary care Background : Tobacco use is the cause of immense burden on our nation in terms of mortality and morbidity , being the single leading cause of preventable illnesses and death . Smoking cessation interventions in our country will be the most cost effective of all interventions considering that the cost incurred on the three main tobacco related illnesses ( COPD , CAD , and Cancer ) being around Rs 27,761 crore in the year 1999 . Matrials and Methods A double blind placebo controlled trial was conducted to see the efficacy of Bupropion in smoking cessation . Smokers with current depression were excluded . The subjects ( n = 30 ) were r and omly assigned to receive Bupropion SR 300 mg/day or placebo for seven weeks . Target quit date was preferentially 8th day of starting the treatment . Intensive counseling was provided by the physician at the baseline and brief counseling at every visit weekly during the treatment phase and at weeks 12 and 16 . Self reported abstinence was confirmed by a carbon monoxide concentration in expired air of less than 10 ppm . Results : The seven-day point prevalence abstinence rate at the end of week 2 and week 16 in the drug group was 46.67 % and 53.33 % respectively and in the placebo group was 13.33 % and 20 % respectively with the ‘ P ’ value of 0.04 and 0.05 respectively . Rates of continuous abstinence at weeks 4 , 7 and 16 were 46.67 % , 40 % and 33.33 % in the drug group and 13.33 % , 13.33 % and 13.33 % in the placebo group respectively . The rates were significantly higher in the drug group till week 4 starting from week 2 of the treatment phase . The mean weight gain in drug group was found to be significant less as compared to the placebo at week 16 ( P = 0.025 ) The mean change of depression scores from the baseline was not significantly different between the two groups at any point of time . The withdrawal symptom score increase from the baseline was not significantly higher at any point of time in the drug group but in the placebo group the increase was significantly higher for seven days after target quit date and at weeks 3 and 4 ( P < 0.05 ) . The most common adverse events in the drug group were insomnia , which was seen in 6 ( 40 % ) patients and dry mouth and /or altered taste in 4 ( 26.67 % ) patients , which was significantly higher as compared to placebo . Predictors of Outcome : The univariate predictors of a successful outcome were the point prevalence abstinence at week 16 were older age ( > 40 years ) , ( P = 0.044 ) and quitter status at week 2 ( P = 0.001 ) . Multivariate predictors in order of importance were Quit status at 2nd week ( P = 0.002 ) and Age > 40 years ( P = 0.031 ) . The combined predictive value of these two variables was found to be 86.3 % . Conclusions : Bupropion helps in smoking cessation . This has been proved by three large multicenter r and omized controlled trials . This study has also reflected the same result in the form of significantly high seven-day point prevalence abstinence at week 16 in the Bupropion group as compared to placebo . Bupropion has a beneficial effect on weight gain and withdrawal symptoms and the benign adverse effects of insomnia and dry mouth or altered taste make it a very effective and cheap treatment for nicotine addiction in smokers BACKGROUND Studies undertaken in academic setting s have shown that bupropion hydrochloride can double the odds of smoking cessation compared with placebo . To assess whether these results are applicable in primary care , we launched a double-blind , placebo-controlled , r and omized trial to be conducted by general practitioners . METHODS We assigned 593 healthy smokers to receive bupropion hydrochloride , 150 mg twice a day , or placebo daily for 7 weeks ( hereinafter , bupropion group [ n = 400 ] and placebo group [ n = 193 ] , respectively ) . After the baseline visit , 4 clinical visits and 3 telephone calls were scheduled over the 1-year period . The primary end points were biochemically confirmed continuous abstinence at week 7 and at week 52 . RESULTS Seventy-one Italian general practitioners enrolled participants from April 2004 to May 2005 . Of the bupropion group , 41.0 % were continuously abstinent from week 4 to week 7 compared with 22.3 % of the placebo group ( multivariate odds ratio , 2.37 ; 95 % confidence interval , 1.60 - 3.53 ) . The continuous abstinence rates from week 4 to week 52 were 25 % in the bupropion group and 14 % in the placebo group ( odds ratio , 2.11 ; 95 % confidence interval , 1.32 - 3.39 ) . The mean weight gain was similar in both groups and among long-term abstainers was 3 kg in women and 4 kg in men . More participants in the bupropion group experienced an adverse event than those in the placebo group , but the percentage who discontinued use of the study medication was similar . CONCLUSIONS Bupropion more than doubled the odds of continuous abstinence from smoking . The adherence of general practitioners and participants to the protocol was excellent , making our findings robust and easy to generalize to the context of primary care BACKGROUND Recent data suggest that women smokers respond differently than men to cessation pharmacotherapies , particularly nicotine replacement therapy ( NRT ) . Lower abstinence and higher relapse rates are often reported for women treated with NRT . Gender effects for those treated with non-nicotinic , bupropion-hydrochloride sustained release for relapse prevention have not been studied . METHODS Data from a multicenter relapse-prevention ( RP ) trial of bupropion ( November 1995-June 1998 ) were analyzed for gender differences . Men and women smokers ( N=784 ) were treated with open-label bupropion for 7 weeks . Those abstinent at Week 7 ( n=432 ) were enrolled in the double-blind relapse-prevention phase and r and omized to placebo or continued bupropion for 45 additional weeks . RESULTS Differences in point-prevalence abstinence rates between men ( 61.8 % ) and women ( 55.6 % ) in open-label bupropion ( Week 7 ) were not significant . In the RP-phase Week 52 , continuous abstinence rates for men and women were 37.8 % and 36.4 % ( bupropion ) and 36.6 % and 29.9 % ( placebo ) , respectively ; point-prevalence abstinence rates for men and women were 54.1 % and 55.9 % ( bupropion ) and 42.9 % and 41.3 % ( placebo ) , respectively . Abstinence rates and time to relapse were superior for both men and women who received longer treatment . Gender differences within treatment groups were not significant . Median time to relapse was equal for men and women within each treatment group : Week 32 for bupropion and Week 20 for placebo . CONCLUSIONS Our data suggest that bupropion is a promising pharmacotherapy for preventing relapse , particularly for women Rationale Fluoxetine improves affect in clinical syndromes such as depression and premenstrual dysphoric disorder . Little is known about fluoxetine ’s influence on mood changes after quitting smoking , which often resemble sub- clinical depression . Objectives The present study , a re- analysis of previously published data ( Niaura et al. 2002 ) , examined fluoxetine ’s effect on changes in negative and positive affect following quitting smoking . Methods Adult smokers ( n=175 ) without clinical ly significant depression were r and omized on a double-blind basis to receive fluoxetine hydrochloride ( 30 or 60 mg daily ) or placebo for 10 weeks in combination with cognitive-behavioral therapy ( CBT ) for smoking cessation . We postulated that fluoxetine would beneficially influence post-cessation changes in positive and negative affect . Results Mood change across treatment was analyzed using mixed linear modeling controlling for initial level of nicotine dependence , plasma fluoxetine metabolites , and change in cotinine ( a nicotine metabolite ) at each visit . Relative to placebo , those on 60 mg fluoxetine experienced an elevation in positive affect that increased across time [ t(526)=2.50 , P=0.01 ] , and a reduction in negative affect that returned to baseline across time [ t(524)=2.26 , P=0.02 ] . There were no differences between 30 mg and placebo on changes in positive or negative affect . Conclusions Results indicate that 60 mg of fluoxetine improves both positive and negative mood states after quitting smoking and that diminished positive affect may be an overlooked affective response to smoking cessation Multiple , controlled clinical trials support the efficacy of nortriptyline as a smoking cessation agent . Although therapeutic plasma nortriptyline concentrations ( PNCs ) are known for the treatment of depression , little is known about PNCs in smoking cessation treatment . PNCs from three r and omized , placebo‐controlled smoking cessation trials ( N=244 ) were analyzed both separately and pooled . PNCs normalized for dose and weight were associated with cigarettes per day and race , but not with sex or age . Greater smoking was associated with decreased normalized PNCs . In addition , both Asian and black population s had significantly higher normalized PNCs than the white population s. Weak and inconsistent associations between PNCs and self‐reported side effects were observed . PNCs were linearly related to end of treatment and long‐term biochemically verified smoking abstinence . Maximum therapeutic effects were observed over a range of plasma concentrations somewhat lower than those found effective for the treatment of depression INTRODUCTION Fluoxetine , a selective serotonin reuptake inhibitor , was examined in the treatment of smokers with elevated depressive symptoms . Specifically , this r and omized , open-label clinical trial was design ed to evaluate the efficacy of three logical , real-world alternatives for providing smoking cessation treatment to smokers with elevated depressive symptoms . METHODS In a sample of 216 smokers ( mean Center for Epidemiological Studies Depression Scale score = 11.41 ) , participants were r and omly assigned to ( a ) transdermal nicotine patch ( TNP ) , beginning on quit date and continuing for 8 weeks thereafter ; ( b ) st and ard administration of antidepressant pharmacotherapy with fluoxetine ( 20 mg ) , beginning 2 weeks before quit date and continuing for 8 weeks following quit date + TNP ( ST-FLUOX ) ; or ( c ) sequential administration of fluoxetine ( 20 mg ) , beginning 8 weeks before quit date and continuing for 8 weeks following quit date + TNP ( SEQ-FLUOX ) . All participants received 5 sessions of brief behavioral smoking cessation treatment . RESULTS Findings indicate that SEQ-FLUOX result ed in significantly higher point prevalence abstinence than ST-FLUOX at 6-month follow-up ( OR = 2.35 ; 95 % CI = 1.10 - 5.02 , p < .03 ) , a difference that was reduced at the 12-month assessment . Furthermore , sequential fluoxetine treatment , compared with st and ard fluoxetine treatment , result ed in significantly lower levels of depressive symptoms throughout smoking cessation treatment ( p < .025 ) and significantly lower nicotine withdrawal-related negative affect ( p < .004 ) immediately after quitting . CONCLUSIONS Findings suggest that if one is going to prescribe fluoxetine for smoking cessation in smokers with elevated depressive symptoms , it is best to begin prescribing fluoxetine well before the target quit date INTRODUCTION Bupropion and cognitive-behavioral treatment ( CBT ) for depression have been used as components of treatments design ed to alleviate affective disturbance during smoking cessation . Studies of treatment-related changes in precessation affect or urges to smoke are needed to evaluate the proposed mechanisms of these treatments . METHODS The present report examines affective trajectories and urges to smoke prior to , on quit day , and after quitting in a sample of 524 smokers r and omized to receive bupropion versus placebo and CBT versus st and ard smoking cessation CBT . RESULTS Bupropion and /or CBT did not affect the observed decreases in positive affect and increases in negative affect prior to cessation . However , on quit day , observed levels of negative affect and urges to smoke were diminished significantly among individuals receiving bupropion . Decreases in positive affect prior to quitting , lower levels of positive affect , and increased levels of negative affect and urges to smoke on quit day were each related to higher risk of smoking lapse . Depression proneness was an independent predictor of lower positive affect and higher negative affect but did not moderate the effects of bupropion on outcomes . In mediational analyses , the effect of bupropion was accounted for in part by lower negative affect and urges to smoke on quit day . DISCUSSION Results support the efficacy of bupropion in reducing relapse risk associated with urges to smoke and negative affect and suggest the need to better underst and the role of low positive affect as a risk factor for early lapse The associations between failure to quit and posttreatment self-efficacy and motivation were examined among 600 African American smokers enrolled in a r and omized trial testing the efficacy of bupropion for smoking cessation . Participants also received brief motivational counseling and were followed for 6 months . Baseline levels of self-efficacy and motivation for all participants were high ( 8.2 and 8.5 on a 10-point scale , respectively ) . Longitudinal analyses indicated that smokers who failed to quit were less likely than quitters to report high self-efficacy and motivation from posttreatment to follow-up . However , examination of mean self-efficacy and motivation scores at posttreatment and follow-up revealed that smokers continued to sustain high self-efficacy and motivation . Mean self-efficacy and motivation scores differed by less than 1 point from baseline levels , even though the majority of participants failed to quit smoking . Results suggest that unsuccessful participation in a smoking cessation program does not meaningfully reduce smokers ’ self-efficacy and motivation to quit OBJECTIVES To examine the feasibility and efficacy of St. John 's Wort ( SJW ) for smoking cessation . DESIGN This one-arm Phase II study utilized an exact two-stage group sequential design with a 1-week run-in period between the start of SJW treatment and the design ated quit date . A total of 37 smokers ( ages 18 - 65 years , smoking > or = 10 cigarettes/day ) were started on SJW . Thirteen failed to make a verified quit attempt on the pre design ated date and were taken off study result ing in 24 evaluable subjects . SETTING Smokers completed clinic visits at a cancer center with interval telephone calls and mailings . INTERVENTION St and ardized SJW , 450 mg capsules taken orally twice daily along with cessation counseling messages . MAIN OUTCOME MEASURES Subjects completed vali date d surveys and a focused physical examination at baseline . Evaluable subjects were defined as those subjects who made a confirmed quit attempt on their " quit date " 1 week following initiation of SJW . Smoking status was determined through self-report and bioverification using carbon monoxide ( CO ) testing . RESULTS Among evaluable subjects , the 12-week quit rate was 37.5 % ( 9/24 ) . Quitters had no significant change in weight from baseline to 12-weeks cessation . Use of SJW was generally well tolerated . CONCLUSIONS Based upon these results ( which suggest that SJW may be effective in maintaining smoking cessation ) and the high compliance and few AEs , we conclude that SJW demonstrates feasibility for use in smoking cessation . If SJW proves to be effective in larger controlled studies , it could represent a less expensive , more readily accessible and well-tolerated agent to promote tobacco cessation This study evaluated a treatment combining bupropion with a novel acceptance and relationship focused behavioral intervention based on the acceptance and relationship context ( ARC ) model . Three hundred and three smokers from a community sample were r and omly assigned to bupropion , a widely used smoking cessation medication , or bupropion plus functional analytic psychotherapy ( FAP ) and acceptance and commitment therapy ( ACT ) . Objective measures of smoking outcomes and self-report measures of acceptance and relationship processes were taken at pretreatment , posttreatment , 6-month , and 1-year follow-up . The combined treatment was significantly better than bupropion alone at 1-year follow-up with 7-day point prevalence quit rates of 31.6 % in the combined condition versus 17.5 % in the medication-alone condition . Acceptance and the therapeutic relationship at posttreatment statistically mediated 12-month outcomes . Bupropion outcomes were enhanced with an acceptance and relationship focused behavioral treatment Polymorphisms in the dopamine D2 receptor ( DRD2 C/T and DRD2 A/G ) and in dopamine beta hydroxylase ( DBH A/G ) have been implicated in modulation of smoking and other reward-seeking behaviours . We hypothesized that these alleles would predict the outcome of nicotine patch therapy for smoking cessation . In 1991 - 93 , we performed a r and omized controlled trial of the nicotine patch on 1686 heavy smokers ( > or = 15 cigarettes/day ) . In 1999 - 2000 , we contacted 1532 of the 1612 subjects still available ; 767 ( 50 % ) completed a question naire and gave a blood sample . In the 755 cases in which DNA was successfully genotyped , we examined associations between the polymorphisms in DRD2 and DBH , and smoking cessation . At 1 week , the patch was more effective for smokers with DRD2 CT/TT genotype [ patch/placebo odds ratio ( OR ) 2.8 , 95 % confidence interval ( CI ) 1.7 - 4.6 ] than with CC ( OR 1.4 , 0.9 - 2.1 ; P for difference in ORs 0.04 ) . Smokers with both DRD2 CT/TT and DBH GA/AA genotypes had an OR of 3.6 ( 2.0 - 6.5 ) compared to 1.4 ( 1.0 - 2.1 ) for others ( P = 0.01 ) . At 12 weeks , the ORs for these genotypic groups were 3.6 ( 1.7 - 7.8 ) and 1.4 ( 0.9 - 2.3 ) , respectively ( P = 0.04 ) . There was no association between patch effectiveness and DRD2 exon 8 . Short-term effectiveness of the nicotine patch may be related to dopamine beta-hydroxylase and dopamine D2 receptor genotype . Our results support the need for further investigation into personalized therapies for smoking cessation based on individual genotype The effectiveness of bupropion SR , a nicotine patch , or both , when co-administered with cognitive-behavioral therapy , on smoking cessation was evaluated under treatment-as-usual conditions in a primary care smoking cessation clinic . Consecutive consenting patients ( n = 189 ) assigned themselves to one of three treatments according to personal preference : nicotine patch ( NTP ; n = 27 ) , bupropion SR ( B ; n = 101 ) , and bupropion SR plus nicotine patch ( B + NTP ; n = 61 ) . Six-month self-reported abstinence rates were 14.8 % , 27.7 % , and 34.4 % , respectively . Odds ratios for 6-month abstinence , with NTP as reference , were 2.2 ( CI = 0.7 - 5.9 ; p = .19 ) for B , and 3.0 ( CI = 0.9 - 9.9 ; p = .07 ) for B + NTP . Resemblance of abstinence pattern and magnitude between this naturalistic study and r and omized clinical trials of bupropion SR may support tentative inferences of stability and generalizability of clinical trial efficacy findings BACKGROUND Since dopaminergic mechanisms appear to be involved in nicotine dependence , we studied the safety and efficacy of the monoamine oxidase B inhibitor selegiline hydrochloride compared with placebo for smoking cessation in nicotine-dependent cigarette smokers . METHODS Forty subjects with DSM-IV nicotine dependence were r and omized to : 1 ) selegiline hydrochloride ( 5 mg p.o . twice daily ) or 2 ) placebo in an 8-week trial . Outcome measures included smoking cessation rates , treatment retention , and medication side effects . RESULTS Selegiline hydrochloride increased trial end point ( week 8) 7-day point prevalence smoking cessation rates ( selegiline hydrochloride , 9/20 [ 45.0 % ] ; placebo , 3/20 [ 15.0 % ] , odds ratio = 4.64 , 95 % CI , 1.02 - 21.00 , p < .05 ) , and smoking cessation rates during the last 4 weeks of the trial ( selegiline hydrochloride , 6/20 [ 30.0 % ] ; placebo , 1/20 [ 5.0 % ] , odds ratio = 8.14 , 95 % CI , 0.88 - 75.48 , p = .07 ) in comparison with placebo . Six-month follow-up 7-day point prevalence smoking cessation rates were reduced compared with trial end point ( selegiline hydrochloride , 4/20 [ 20.0 % ] ; placebo , 1/20 [ 5.0 % ] , odds ratio = 4.75 , 95 % CI , 0.48 - 46.91 , p = .18 ) . Treatment retention was similar between drug and placebo groups ( p = .13 ) , and selegiline hydrochloride was well tolerated in cigarette smokers . CONCLUSION This preliminary study suggests that selegiline ( 10 mg/day ) is safe for use and enhances smoking cessation rates compared with placebo in nicotine-dependent cigarette smokers Background The double-blind placebo-controlled design is commonly considered the gold st and ard in research methodology ; however , subject expectation bias could subvert blinding . Objective The primary aim of this study was to examine the impact of expectation bias . Specifically , we examined perceived treatment assignment on smoking cessation outcome rates among participants enrolled in a clinical trial of bupropion ( 150 mg SR , BID ) . Design Analyses were conducted on data collected during “ Kick It at Swope , ” a double-blind , placebo-controlled , r and omized trial of 600 African-American smokers . Chi-square and multiple logistic regression analyses were used to examine the impact of perception of assignment on treatment effect and cotinine-verified smoking abstinence rates . Participants Participants were predominantly middle-aged ( mean 44.7 , SD 11.2 ) , African-American women ( 68.6 % ) , who smoked 19 CPD ( SD = 8.1 ) . Most had completed at least a high school education or GED ( 51.6 % ) , and 55 % had a monthly family income < $ 1,800 . Measurements At week 6 ( end of treatment ) and week 26 ( end of study ) , participants were asked to report their perceived treatment group assignment . Self-reported abstinence ( weeks 6 and 26 ) was confirmed using CO and cotinine biochemical verification . Results After adjusting for actual treatment assignment , age and baseline cotinine , participants who perceived being assigned to bupropion vs. placebo were more likely to be abstinent at weeks 6 ( OR = 2.07 , 95 % CI : 1.29 to 3.33 , p = 0.002 ) and 26 ( OR = 1.85 , 95 % CI : 1.05 to 3.24 , p = 0.032 ) . Conclusions Results support previous research that expectation bias associated with judgment of treatment assignment is a strong predictor of outcome and confirms this relationship in a smoking cessation trial using bupropion SR among African-American smokers We conducted a double-blind pilot study involving 11 alcohol- and nicotine-dependent patients r and omized to receive either bupropion or placebo . Four of six patients on bupropion and one of five patients on placebo were abstinent from smoking at the end of medication phase . Those in the bupropion group reported significantly less craving ( p < .02 ) and less exposure to cigarette smoke over time ( expired carbon monoxide ; p < .01 ) . There were no serious adverse events and no main effects of medication group on either per subject or total number of adverse events . All those who completed treatment remained abstinent from alcohol Fluoxetine 's effect ( 30 mg , 60 mg , and placebo ) on postcessation weight gain was studied among participants from a r and omized , double-blind 10-week smoking cessation trial who met strict criteria for abstinence and drug levels . It was hypothesized that ( a ) fluoxetine would dose-dependently suppress postcessation weight gain and ( b ) drug discontinuation would produce dose-dependent weight rebound . During the on-drug phase , placebo participants gained weight linearly ( M = 2.61 kg ) . exceeding both fluoxetine groups ( 30-mg group M = 1.33 kg , 60-mg group M = 1.25 kg ) . Weight suppression was initially greater for 60 mg than 30 mg , but both were followed by weight gain . Six months off drug produced greater dose-dependent weight rebound for 60 mg than 30 mg or placebo . Considering both on- and off-drug phases , weight gain for 60 mg of fluoxetine ( M = 6.5 kg ) was comparable with that for placebo ( M = 4.7 kg ) but greater than that for 30 mg ( M = 3.6 kg ) . Fluoxetine appears to forestall postcessation weight gain , allowing time for the weight-conscious smoker to focus on quitting smoking rather than on preventing weight gain BACKGROUND No pharmacotherapies have been shown to increase long-term ( > or = 6 months ) tobacco abstinence rates among smokeless tobacco ( ST ) users . Bupropion SR has demonstrated potential efficacy for ST users in pilot studies . We conducted a multicenter , r and omized , double-blind , placebo-controlled , clinical trial to assess the efficacy and safety of bupropion SR for tobacco abstinence among ST users . METHODS Adult ST users were r and omized to bupropion SR titrated to 150 mg twice daily ( N=113 ) or placebo ( N=112 ) for 12 weeks plus behavioral intervention . The primary endpoint was the 7-day point-prevalence tobacco abstinence rate at week 12 . Secondary outcomes included prolonged and continuous tobacco abstinence rates , craving and nicotine withdrawal , and weight gain . RESULTS The 7-day point-prevalence tobacco abstinence rates did not differ between bupropion SR and placebo at the end treatment ( 53.1 % versus 46.4 % ; odds ratio ( OR ) 1.3 ; p=0.301 ) . The 7-day point-prevalence abstinence did not differ at weeks 24 and 52 . The prolonged and continuous tobacco abstinence rates did not differ at weeks 12 , 24 , and 52 . A time-by-treatment interaction was observed in craving over time with greater decreases in the bupropion SR group . At 12 weeks , the mean ( + /-S.D. ) weight change from baseline among abstinent subjects was an increase of 1.7 (+/-2.9)kg for the bupropion SR group compared to 3.2 (+/-2.7)kg for placebo ( p=0.005 ) . CONCLUSIONS Bupropion SR did not significantly increase tobacco abstinence rates among ST users , but it significantly decreased craving and weight gain over the treatment period AIMS To examine the effectiveness of transdermal selegiline for producing cigarette smoking abstinence . DESIGN Adult smokers were r and omly assigned to receive selegiline transdermal system ( STS ) or placebo given for 8 weeks . All participants received cognitive behavior therapy ( CBT ) . Follow-ups were conducted at 25 and 52 weeks . SETTING Community smoking cessation clinic . PARTICIPANTS 243 adult smokers ( > or = 18 years of age ; > or = 10 cigarettes/day ) . MEASURES Expired-air carbon monoxide confirmed 7-day point prevalence abstinence . FINDINGS STS was not superior to placebo . More women than men were abstinent at 52 week follow-up ( 28 % vs 16 % , P < 0.05 ) . Behavioral activation ( BAS ) moderated treatment response ( P = 0.01 ) . The survival rate through week 52 for those with high ' drive ' scores on the BAS was 47 % if assigned to selegiline and 34 % if assigned to placebo . The survival rate for those with low ' drive scores ' on the BAS was 35 % if assigned to selegiline compared to 53 % if assigned to placebo . CONCLUSION Transdermal selegiline does not appear generally effective in aiding smoking cessation though there may be a selective effect in those smokers with low ' behavioral activation ' PURPOSE To determine whether ( 1 ) tailored nicotine patch therapy that is based on smoking rate can be carried out in a multisite oncology investigative group practice setting , ( 2 ) long-term use of bupropion reduces the rate of relapse to smoking in smokers who stop smoking with nicotine patch therapy , and ( 3 ) bupropion can initiate smoking abstinence among smokers who have failed to stop smoking after nicotine patch therapy . PARTICIPANTS AND METHODS Fourteen North Central Cancer Treatment Group sites recruited generally healthy adult smokers from the general population for nicotine patch therapy and based the patch dosage on smoking rates . At completion of nicotine patch therapy , nonsmoking participants were eligible to be assigned to bupropion or placebo for 6 months ( for relapse prevention ) . and smoking participants were eligible to be assigned to bupropion or placebo for 8 weeks of treatment . RESULTS Of 578 subjects , 31 % were abstinent from smoking at the end of nicotine patch therapy . Of those subjects not smoking at the end of nicotine patch therapy who entered the relapse prevention phase , 28 % and 25 % were not smoking at 6 months ( the end of the medication phase ) for bupropion and placebo , respectively ( P = .73 ) . For those still smoking at the end of nicotine patch therapy , 3.1 % and 0.0 % stopped smoking with bupropion or placebo , respectively ( P = .12 ) . CONCLUSION Tailored nicotine patch therapy for the general population of smokers can be provided in a multisite oncology investigative group setting . Bupropion did not reduce relapse to smoking in smokers who stopped smoking with nicotine patch therapy . Bupropion did not initiate abstinence among smokers who failed to stop smoking with nicotine patch therapy OBJECTIVES To determine the differential cost effectiveness of 2 dosing regimens of bupropion sustained release ( SR ) in combination with behavioral interventions of minimal intensity ( tailored mailings [ TM ] ) or moderate intensity ( proactive telephone calls [ PTC ] ) for smoking cessation in an actual practice setting . STUDY DESIGN Open-label , r and omized trial , with 1-year follow-up , conducted in a large health system based in Seattle , Washington . METHODS A total of 1524 adult smokers interested in quitting smoking were r and omly assigned to receive 150 mg bupropion SR daily and PTC ( n = 382 ) , 150 mg bupropion SR daily and TM ( n = 381 ) , 300 mg bupropion SR daily and PTC ( n = 383 ) , or 300 mg bupropion SR daily and TM ( n = 378 ) . Sufficient medication for 8 weeks of dosing was provided to patients . The primary outcome measure was self-reported point-prevalence 7-day nonsmoking status at 12 months after the target quit date . RESULTS Although the 300-mg dose was associated with a higher 12-month nonsmoking rate relative to the 150-mg dose with both PTC and TM , the additional cost result ed in lower cost effectiveness . The PTC behavioral intervention was more expensive than TM , but the additional effectiveness result ed in almost equivalent cost effectiveness at the 150-mg dose . Costs per additional 12-month nonsmoker ( above that expected for placebo ) for the 150-mg dose groups averaged 950 dollars and per additional lifetime quitter averaged 1508 dollars ; for the 300-mg groups these costs were 1342 dollars and 2129 dollars , respectively . Cost per life-year and quality -adjusted life-years ( QALYs ) saved varied substantially by age and treatment , but were no greater than 1100 dollars for all treatment groups when averaged across the age and sex distribution for the study population . CONCLUSIONS Although the cost per life-year and QALYs saved were sufficiently low for all doses to rate these smoking cessation interventions as among the most cost effective of life-saving medical treatments , within the regimens tested 150 mg bupropion combined with either PTC or TM was the most cost effective AIMS To examine heterogeneity in outcome following treatment for smoking cessation with combined bupropion SR and behavioral counseling in women and men . DESIGN , SETTING , PARTICIPANTS This study included 875 women and 649 men recruited from a large health-care system and r and omized to one of four combinations of treatment [ two dosage levels of bupropion SR ( Zyban , 150 mg and 300 mg ) were crossed with two counseling programs of lower and higher intensity to create a four-cell design ] . MEASUREMENTS AND FINDINGS A comprehensive set of relevant individual characteristics prior to treatment and treatment characteristics was included in the analysis . Smoking outcome at 12 months was defined as point-prevalence of any regular smoking within the 7 days prior to follow-up contact . Classification and regression tree analysis identified six subgroups in women that ranged in proportion of non-smokers from 9.8 % to 42.9 % and six subgroups in men that ranged in proportion of non-smokers from 17.3 % to 50.0 % . CONCLUSIONS These results indicate the presence of a substantial amount of variation in treatment outcome among women and men receiving combined bupropion SR and counseling . Variation in outcome could be reduced by providing treatments tailored to subgroups of individuals who are at exceptionally high risk for smoking following cessation Despite changes in smoking behavior , one-third of the Danish population continues to smoke . Many of these smokers are hospital employees . This 6-month , multicenter , parallel group , r and omized , double-blind , placebo-controlled study evaluated treatment with bupropion hydrochloride sustained release ( Zyban ) compared with placebo as an aid to smoking cessation in health care workers . A total of 336 hospital employees who smoked at least 10 cigarettes daily were r and omized ( 2:1 ) to 7 weeks of treatment with bupropion ( n=222 ) or placebo ( n=114 ) . All participants were motivated to quit smoking and received behavioral counseling . Continuous smoking abstinence during weeks 4 - 7 was the primary endpoint , and long-term smoking abstinence was among the secondary endpoints . Of the original participants , 212 completed the 6-month trial . Continuous smoking abstinence at week 7 was achieved by 43 % in the bupropion group and 18 % in the placebo group , p<.001 . After 26 weeks , 18 % and 7 % , respectively , were continuously abstinent , p=.008 . Side-effects were frequent but simple and reversible in both groups , and generally consistent with the findings of previous studies . Dizziness , insomnia , and pruritus appeared more frequently in the bupropion group than in the placebo group . Bupropion was effective as an aid to smoking cessation in a broad group of hospital employees in Denmark AIM The primary aim of this study was to determine the safety and efficacy of the monoamine oxidase-B ( MAO-B ) inhibitor selegiline hydrochloride ( SEL , l-Deprenyl ; Eldepryl ) as an aid for smoking cessation in cigarette smokers . METHODS One hundred and one nicotine-dependent adult cigarette smokers without current psychiatric or substance use disorders participated in this 8-week r and omized , double-blind , placebo-controlled trial . Participants received either SEL ( 5 mg bid , n=51 ) or placebo ( PLO , n=50 ) , in combination with brief ( < 10 min ) manualized smoking cessation counseling . The main smoking outcome measures were 7-day point prevalence abstinence at end of trial ( EOT ) , 4-week continuous smoking abstinence at end of trial ( CA ) , and 7-day point prevalence abstinence at 6-month follow-up ( 6MFU ) . Abstinence was determined by an absence of self-reported cigarette smoking and biochemically verified by expired breath carbon monoxide and plasma cotinine levels . RESULTS Rates of smoking abstinence did not differ by medication group ( EOT : SEL=16 % , PLO=20 % , p=0.57 ; CA : SEL=14 % , PLO=18 % , p=0.56 ; 6MFU : SEL=12 % , PLO=16 % , p=0.54 ) . Adverse events were modest and comparable between medication groups . Participants receiving SEL were more likely than those receiving PLO to report dry mouth ( 25.5 % versus 8.2 % , p<0.05 ) . CONCLUSIONS Our results suggest that SEL was safe and well-tolerated by adult cigarette smokers , but did not improve smoking abstinence rates compared to PLO A population pharmacokinetic and pharmacodynamic analysis evaluated the relationships of dose , plasma concentrations of bupropion and metabolites , and patient covariates with the safety and efficacy of bupropion sustained release ( SR ) for smoking cessation . A total of 519 outpatient chronic cigarette smokers were r and omized to one of three bupropion SR doses : 100 , 150 , or 300 mg/day or placebo . The bupropion plasma concentration time data were fit and subject-specific bayesian estimates of clearance were obtained . Logistic regression analyses evaluated the role of dose , concentrations , and covariates in predicting efficacy and safety endpoints . For the evaluation of efficacy , patients were classified as quitters or non-quitters on the basis of a 4-week quit variable ( defined as complete abstinence for weeks 4 - 7 of the study ) . For the evaluation of safety , patients were classified into two categories for each adverse event evaluated , corresponding to whether the patient ever experienced the adverse event during the course of the study or never experienced the event , regardless of whether the event was treatment-emergent . The efficacy of bupropion SR in facilitating smoking cessation was found to be related to dose and a mean metabolite concentration , and quitting in general was found to be related to the number of cigarettes smoked per day at baseline . Smoking cessation was 1.42 , 1.69 , and 2.84 times more likely in patients receiving 100 , 150 , and 300 mg/day of bupropion SR , respectively , as compared to placebo ( p = 0.0001 ) . As the baseline number of cigarettes smoked per day increased , the likelihood of quitting decreased regardless of the treatment condition . Insomnia and dry mouth were positively associated with mean metabolite concentrations , and dry mouth was inversely related to patient weight . Anxiety was inversely related to predicted steady-state concentration ( Cpss ) , suggesting a positive effect on this withdrawal symptom . Bupropion SR exhibits a statistically significant dose/plasma level-response relationship for smoking cessation . Dry mouth and insomnia , related to concentrations , may be managed with dose reduction , with the realization that smoking cessation may be impaired Abstract Objective : To assess the efficacy and safety of a repeat course of treatment with transdermal nicotine for cessation of smoking in a brief intervention setting . Study design : R and omised , double blind , placebo controlled trial with follow up for 26 weeks . Subjects : 629 smokers who had unsuccessfully attempted to stop smoking by using active transdermal nicotine and brief behavioural counselling . Smokers were motivated to quit smoking for a second time and smoked > /=15 cigarettes a day . Interventions : Twelve weeks ' treatment with active transdermal nicotine patches or placebo and brief counselling at monthly visits . Main outcome measure > : Sustained smoking cessation for the 28 days before the visit at week 12 verified by expired carbon monoxide concentrations . Results : At 12 weeks 21/315 ( 6.7 % ) subjects allocated to active treatment had stopped smoking compared with 6/314 ( 1.9 % ) allocated to placebo ( absolute difference 4.7 % ; 95 % confidence interval 1.6 % to 7.9 % ; P=0.003 ) . At 26 weeks the rates were 20/315 ( 6.4 % ) and 8/314 ( 2.6 % ) ( 3.8 % ; 0.6 % to 7.0 % ; P=0.021 ) . Difficulty in sleeping was reported by 43/179 ( 24.0 % ) on active treatment and 19/143 ( 13.3 % ) on placebo ( P=0.015 ) . Severe reactions at the site of application were rare ( 6/322 ; 1.9 % ) . Conclusions : Repeated treatment with transdermal nicotine together with brief counselling can improve the low success rates of smoking cessation in recently relapsed , moderate to heavy smokers . Questions remain about whether more intensive interventions or higher doses of nicotine could be more effective . The likelihood of severe reactions at the site of application with repeated treatment is low In this double-blind , placebo-controlled smoking cessation treatment study , 608 participants were r and omly assigned to receive active bupropion and active 4-mg gum ( AA , n = 228 ) , active bupropion and placebo gum ( AP , n = 224 ) , or placebo bupropion and placebo gum ( PP , n = 156 ) . Relative to the PP group , the AA and AP groups were each significantly more likely to be abstinent at 1 week , end of treatment , and 6 months but not at 12 months postquit . After the first week postquit there were no differences in abstinence rates between the AA and AP groups . We found no significant individual difference variables that moderated outcome beyond 1 week postquit To date , only one study has been published on individual characteristics associated with outcome following st and ard treatment with bupropion SR for smoking cessation . To investigate treatment outcome beyond the 6-week end-of-treatment point , the present study examined characteristics associated with more clinical ly relevant smoking endpoints following treatment with bupropion SR in a large health care system . A total of 1,524 smokers ( 649 men and 875 women ) of average age 45.1 years were r and omized to receive one of four combinations of bupropion SR ( 150 or 300 mg ) and behavioral counseling ( tailored mailings or proactive telephone counseling ) and assessed for point-prevalent smoking status at 3 and 12 months . Multiple logistic regression analyses of potential risk factors for 12-month point-prevalent smoking and for persistent smoking ( point-prevalent smoking at both follow-ups ) following treatment were conducted for men and women combined and separately . Risk factors for smoking at both endpoints in the combined sample included treatment with tailored mailings , female gender , younger age , higher levels of tobacco dependence , shorter previous quit attempts , previous use of nicotine replacement therapy , and report of current depressive symptoms or lifetime depression . Risk factors for smoking following treatment identified in women only included treatment with the lower dose of bupropion SR , younger age , and higher perceived stress , whereas those that were unique to men included the presence of lifetime depression . The results are discussed in terms of their implication s for the need for more effective treatments in general , and the role of individual differences in the likelihood of returning to smoking following treatment for quitting Abstract Aim : To examine heterogeneity in outcome at 12 months following 8 weeks of treatment for smoking cessation with bupropion sustained-release ( SR ) 150 or 300 mg/day combined with behavioural counselling . Design , setting , participants : Smokers were recruited from a large healthcare system and then r and omized to receive either bupropion SR 150 mg/day ( n = 763 ) or 300 mg/day ( n = 761 ) taken for 8 weeks in combination with either proactive telephone counselling or a tailored mail approach . Measurements and findings : A comprehensive set of relevant individual pre-treatment and treatment characteristics was included in the analysis . Smoking outcome at 12 months was defined as point-prevalence of any regular self-reported smoking within the 7 days prior to follow-up contact . Classification and regression tree analysis identified subgroups that varied with respect to likelihood of being nonsmokers at 12 months . Seven subgroups were identified among those receiving bupropion SR 150 mg/day ( proportion of nonsmokers at 12 months ranged from 13.7 % to 43.5 % ) and eight subgroups among those receiving bupropion SR 300 mg/day ( proportion of nonsmokers at 12 months ranged from 9.6 % to 51.7 % ) . In the 150-mg/day group , those with the lowest rate reported no previous quit attempt of 1 month or more in duration while those with the highest rate all reported previous quit attempts of 1 month or longer . In the 300 mg/day group , those with the lowest rate had very high levels of dependence while those with the highest rate were more highly educated and smoked at a lower level . Across all subgroups , cost per 12-month quitter ranged from a low of $ US302 to a high of $ US2502 . Conclusions : These results indicate the presence of a substantial amount of variation in outcome following treatment with both dosages of bupropion SR , with substantial cost consequences . Variation in outcome could be reduced by providing treatments tailored to subgroups of individuals who are at exceptionally high risk for smoking following a quit attempt The objective of this study was to assess the concurrent validity of the FTQ-ST and the DIS-IV diagnosis of nicotine dependence among 68 adult ST users enrolled in a r and omized , controlled clinical trial of bupropion SR . FTQ-ST scores were not found to differ between those with and without a current DIS-IV diagnosis of nicotine dependence ( 7.4+/-2.1 vs. 6.8+/-2.8 , P=0.325 ) . For all possible FTQ-ST cutoff scores , the observed agreement between the FTQ-ST and the DIS-IV was not found to be different from that expected due to chance . FTQ-ST total scores were positively correlated with serum cotinine ( Spearman 's r=0.40 , P<0.001 ) , amount of tobacco used ( r=0.51 and r=0.41 for average dips/chews per day ; average tins/pouches per week , respectively , P<0.001 ) , and a reduced likelihood of abstinence at 3 months ( OR=0.76 , 95 % C.I. 0.61 - 0.96 ; P=0.019 ) . Participants meeting DIS-IV criteria had lower cotinine concentrations than those without this diagnosis ( 411+/-263 ng/ml vs. 493+/-246 ng/ml ; P=0.042 ) . Poor concordance was observed between the FTQ-ST and the DIS-IV in the assessment of nicotine dependence in ST users Although bupropion is known to be an effective aid to smoking cessation , little is known about its mode of action . In the present study we tested the hypothesis that bupropion reduces the likelihood that a smoking lapse , or slip , leads to a subsequent relapse . This hypothesis was tested in the context of a clinical trial of bupropion as a smoking cessation aid , using Cox regression and representing lapse history as a discrete time-varying covariate . Bupropion treatment reduced the probability of relapse during the treatment phase ( hazard ratio , or HR=.421 , p < or = .000 ) but not during the follow-up phase ( end of treatment to 6 months , HR=.896 , p < or=.67 ) . As anticipated , having small lapses during treatment contributed to or predicted subsequent relapse , both during treatment ( HR=2.897 , p < or = .000 ) and during follow-up ( HR=2.320 , p < or=.008 ) . Although an interaction was found between drug treatment and lapse history in predicting subsequent failure during the treatment phase , the finding suggested that drug slightly increased the effect of lapse on eventual failure during treatment ( HR=1.706 , p < or=.012 ) . No evidence was found that the effect of this interaction carried forward into follow-up ( HR=1.500 , p < or=.30 ) . Although the mechanisms of action of bupropion may best be addressed in a human laboratory study , results from this clinical trial suggest that the effectiveness of bupropion treatment is not attributable to reducing the effect of a lapse in predicting relapse BACKGROUND / AIMS Smoking cessation has been shown to be effective in r and omized controlled trials . It is unclear though , whether interventions also work in routine primary care . METHODS In 167 primary care setting s we conducted a r and omized four-armed smoking cessation trial to examine the efficacy of a minimal intervention ( MI ; n = 81 ) , cognitive-behavioral therapy ( CBT ; n = 175 ) , bupropion ( BUP ; n = 108 ) and nicotine replacements ( NRT ; n = 103 ) . Overall , 467 current smokers were enrolled . Abstinence rates at the end of treatment ( 12 weeks ) were 32.8 % for MI patients , 34.8 % for CBT , 35.3 % for NRT , and 46.5 % for BUP patients ( ITT , intention to treat ) ( no differential effects ) . Retention rates were highest in the BUP group ( 59.3 % ) and lowest in the NRT group ( 50.5 % ) . Completer findings were : MI , 56.4 % ; CBT , 64 % ; BUP , 79.3 % ; NRT , 69.2 % ( LOCF , lost to follow-up ) . No serious adverse events occurred during or after the medication phase . At 12-month follow-up continuous abstinence rates were : BUP , 29.0 % ; CBT , 20.9 % ; NRT , 29.6 % ; MI , 29.6 % . CONCLUSION Our findings suggest that established smoking cessation treatments are effective when applied by non-specialist primary care physicians . Our data supports a structured , multimodal treatment structure as core ingredient of successful smoking cessation in primary care OBJECTIVE Two smoking cessation studies provided venues to 1 ) look for differences in affective symptoms between cigarette smokers with and without a history of major depression or other psychiatric diagnoses who were not currently depressed and 2 ) evaluate the efficacy of fluoxetine in ameliorating affective symptoms in smokers with a history of major depression but not currently depressed . METHOD Part I : Three hundred sixty-eight smokers who enrolled in a smoking cessation treatment study completed baseline self-rating scales . The relationship between the scale scores and a history of major depression and other psychiatric diagnoses was examined . Part II : Thirty-nine smokers with a history of major depression were enrolled in a r and omized , double-blind study that examined the utility of fluoxetine as an aid to smoking cessation . Self-rated scales were compared at baseline and after 3 weeks of medication treatment before the attempt to quit . RESULTS A history of major depression had significant main effects across all scale scores ; subjects with such a history rated themselves as more symptomatic . The effects of other psychiatric diagnoses were neither as pervasive nor as robust . There were no differences in baseline scores between the fluoxetine- and placebo-treated groups and no change within the placebo group after 3 weeks . There was significant improvement from baseline in several subscale scores for the group treated with fluoxetine . However , comparison of the score changes for the placebo and fluoxetine groups did not show a statistically significant difference , which limited the ability to conclude that active treatment was better than placebo . CONCLUSIONS Subjects with a history of major depression , but without current affective illness , reported themselves to be more symptomatic than those without such-a history . Furthermore , in a group of smokers with a history of major depression , affective symptoms , without concurrent syndromal illness , may be ameliorated by treatment with fluoxetine INTRODUCTION Underst and ing the mechanisms by which bupropion promotes smoking cessation may lead to more effective treatment . To the extent that reduced smoking reinforcement is one such mechanism , a longer duration of pre quit bupropion treatment should promote extinction of smoking behavior . We evaluated whether 4 weeks of pre quit bupropion ( extended run-in ) results in greater pre quit reductions in smoking rate and cotinine and , secondarily , greater short-term abstinence , than st and ard 1 week of pre quit bupropion ( st and ard run-in ) . METHODS Adult smokers ( n = 95 ; 48 females ) were r and omized to a st and ard run-in group ( n = 48 ; 3-week placebo , then 1-week bupropion pre quit ) or an extended run-in group ( 4-week pre quit bupropion ; n = 47 ) . Both groups received group behavioral counseling and 7 weeks of post quit bupropion . Smoking rate ( and craving , withdrawal , and subjective effects ) was collected daily during the pre quit period ; biochemical data ( cotinine and carbon monoxide ) were collected at study visits . RESULTS During the pre quit period , the extended run-in group exhibited a greater decrease in smoking rate , compared to the st and ard run-in group , interaction p = .03 . Cigarette craving and salivary cotinine followed a similar pattern , though the latter was evident only among women . Biochemically verified 4-week continuous abstinence rates were higher in the extended run-in group ( 53 % ) than the st and ard run-in group ( 31 % ) , p = .033 . CONCLUSIONS The extended use of bupropion prior to a quit attempt reduces smoking behavior during the pre quit period and improved short-term abstinence rates . The data are consistent with an extinction-of-reinforcement model and support further investigation of extended run-in bupropion therapy for smoking cessation OBJECTIVES For smoking cessation , physical activity ( PA ) may help manage withdrawal symptoms , mood , stress , and weight ; yet studies of PA as an aid for smoking cessation have been mixed . This study examined : ( 1 ) the impact of an extended relapse prevention program on increasing moderate to vigorous PA ( MVPA ) in adults enrolled in a tobacco cessation treatment trial ; ( 2 ) whether changes in MVPA were associated with sustained abstinence from smoking ; and ( 3 ) mechanisms by which MVPA may support sustained abstinence from smoking . METHODS In a r and omized controlled trial conducted from 2003 - 2006 in San Francisco , California , 407 adult smokers received a 12 week group-based smoking cessation treatment with bupropion and nicotine patch with the quit date set at week 3 . At week 12 , participants were r and omized to no further treatment or to 40 weeks of bupropion or placebo with or without an 11-session relapse prevention intervention of which 2 sessions ( held at weeks 16 and 20 ) focused on PA . Participants receiving the PA intervention ( n=163 ) received a pedometer , counseling to increase steps 10 % biweekly towards a 10,000 steps/day goal , and personalized reports graphing progress with individualized goals . The International Physical Activity Question naire assessed weekly minutes of MVPA at baseline and weeks 12 and 24 . Sustained abstinence from tobacco at week 24 was vali date d with expired carbon monoxide . RESULTS In a repeated mixed model analysis , intervention participants significantly increased their MVPA relative to control participants , F(1,475)=3.95 , p=.047 . Pedometer step counts also increased significantly , t(23)=2.36 , p=.027 , though only 15 % of intervention participants provided 6 weeks of pedometer monitoring . Controlling for treatment condition , increased MVPA predicted sustained smoking abstinence at week 24 , odds ratio=1.84 ( 95 % CI : 1.07 , 3.05 ) . Among participants with sustained abstinence , increased MVPA was associated with increased vigor ( r=0.23 , p=.025 ) and decreased perceived difficulty with staying smoke-free ( r=-0.21 , p=.038 ) . CONCLUSION PA promotion as an adjunct to tobacco treatment increases MVPA levels ; changes in MVPA predict sustained abstinence , perhaps by improving mood and self-efficacy This study assessed the relationship between beliefs about drug assignment and abstinence status in two treatment studies using nortriptyline hydrochloride as an adjunct to smoking cessation . Smokers ( N = 345 ) drawn from two clinical trials were asked at the final follow-up ( FFU ) at 52 or 64 weeks whether they believed they had received active or placebo drug . Responses were obtained from 262 participants , or 76 % of the sample . Biochemically verified abstinence was collected at end of treatment ( EOT ) and FFU . In both studies , participants were correct in guessing drug assignment . At FFU , belief about drug assignment was not related to abstinence for either active or placebo participants . Participants who received active drug and who were smoking at EOT were more likely to believe they had received placebo than active drug participants who were abstinent at EOT . We found no significant relationship between belief about drug and abstinence status for placebo participants at EOT . Baseline variables did not significantly predict correctness of drug identification . Participants who experienced drug side-effects not easily attributable to nicotine withdrawal were more likely to identify their drug assignment as nortriptyline . We conclude that experience during the active treatment period , including side-effects and treatment success , may be related to belief about drug assignment , that the field would be well served by at least two assessment s of blindness in clinical trials , and that discrepancy between these findings and those regarding nicotine replacement therapy may be related to differences in dependent variables BACKGROUND AND METHODS Use of nicotine-replacement therapies and the antidepressant bupropion helps people stop smoking . We conducted a double-blind , placebo-controlled comparison of sustained-release bupropion ( 244 subjects ) , a nicotine patch ( 244 subjects ) , bupropion and a nicotine patch ( 245 subjects ) , and placebo ( 160 subjects ) for smoking cessation . Smokers with clinical depression were excluded . Treatment consisted of nine weeks of bupropion ( 150 mg a day for the first three days , and then 150 mg twice daily ) or placebo , as well as eight weeks of nicotine-patch therapy ( 21 mg per day during weeks 2 through 7 , 14 mg per day during week 8 , and 7 mg per day during week 9 ) or placebo . The target day for quitting smoking was usually day 8 . RESULTS The abstinence rates at 12 months were 15.6 percent in the placebo group , as compared with 16.4 percent in the nicotine-patch group , 30.3 percent in the bupropion group ( P<0.001 ) , and 35.5 percent in the group given bupropion and the nicotine patch ( P<0.001 ) . By week 7 , subjects in the placebo group had gained an average of 2.1 kg , as compared with a gain of 1.6 kg in the nicotine-patch group , a gain of 1.7 kg in the bupropion group , and a gain of 1.1 kg in the combined-treatment group ( P<0.05 ) . Weight gain at seven weeks was significantly less in the combined-treatment group than in the bupropion group and the placebo group ( P<0.05 for both comparisons ) . A total of 311 subjects ( 34.8 percent ) discontinued one or both medications . Seventy-nine subjects stopped treatment because of adverse events : 6 in the placebo group ( 3.8 percent ) , 16 in the nicotine-patch group ( 6.6 percent ) , 29 in the bupropion group ( 11.9 percent ) , and 28 in the combined-treatment group ( 11.4 percent ) . The most common adverse events were insomnia and headache . CONCLUSIONS Treatment with sustained-release bupropion alone or in combination with a nicotine patch result ed in significantly higher long-term rates of smoking cessation than use of either the nicotine patch alone or placebo . Abstinence rates were higher with combination therapy than with bupropion alone , but the difference was not statistically significant 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 In a placebo-controlled bupropion smoking cessation trial , we examined blind integrity , the link between blind integrity and quit rates , and whether side effects and changes in nicotine withdrawal symptoms or mood were mechanisms through which blind integrity is threatened . At a 12-month follow-up , 498 participants indicated whether they thought they received bupropion , placebo , or were not sure . Potential mediators of treatment effects on treatment arm guess ( i.e. , side effects , withdrawal , and mood ) were measured during treatment , and 7-day point prevalence cessation was assessed at the end of treatment ( EOT ) and at 6 and 12 months after quit date . Overall , 55 % of participants guessed their r and omization correctly . Compared to guessing not sure , participants who guessed they were taking bupropion were more than twice as likely to have been r and omized to bupropion . Similarly , participants who guessed placebo were twice as likely to have been r and omized to placebo . Treatment arm guess was associated with quit rates . Including treatment arm guess with actual treatment arm in models of quit rates significantly reduced the odds ratio for bupropion efficacy at the EOT and at 6 and 12 months after quit date . There was no evidence for mediation . In bupropion smoking cessation trials , blind failure may occur and participant guess about treatment arm assignment is associated with quit rates The authors examined whether serum fluoxetine levels influence behavioral treatment adherence and smoking cessation outcome . Nondepressed smokers ( N = 989 ) from 16 centers were r and omized on a double-blind basis to receive either fluoxetine ( 30 or 60 mg ) or placebo plus 9 sessions of behavioral smoking cessation treatment . Fluoxetine and norfluoxetine blood levels were assayed 1 week after the quit date . Logistic regression was used to predict treatment completion and cessation outcome , controlling for gender , age , treatment site , and degree of nicotine dependence . Higher steady-state fluoxetine blood levels ( fluoxetine + norfluoxetine ) predicted less likelihood of dropping out , chi2(1 , N = 820 ) = 3.9 , p < .05 , and more likelihood of being abstinent , chi2(1 , N = 513 ) = 18.1 , p < .001 . Attaining a higher fluoxetine blood level improved the likelihood of completing behavioral treatment and increased the probability of achieving abstinence INTRODUCTION Studies examining the efficacy of tobacco dependence treatment among recovering alcoholic smokers have produced mixed findings . We set out to investigate this issue further by conducting a r and omized , double-blind , placebo-controlled trial of bupropion sustained-release ( SR ) for smoking relapse prevention among abstinent alcoholic smokers . METHODS Participants ( N = 195 ) met DSM-IV criteria for a history of alcohol abuse or dependence and had at least 1 year of continuous abstinence from alcohol and drugs . Open-label treatment with nicotine patch therapy was provided to all subjects for 8 weeks . The initial nicotine patch dose was determined by the subject 's baseline serum cotinine concentration with an aim to achieve 100 % cotinine replacement . All subjects who were confirmed abstinent from smoking throughout the final week of nicotine patch therapy ( Week 8) were r and omly assigned to receive bupropion SR 300 mg/day or placebo through Week 52 . RESULTS A total of 110 participants were r and omized to the double-blind treatment . No significant difference was observed between the bupropion and placebo groups for rates of continuous smoking abstinence , 41.1 % ( 95 % CI = 28.1%-55.0 % ) versus 40.7 % ( 95 % CI = 27.6%-55.0 % ) , respectively , p = 1.0 , or point prevalence abstinence , 39.3 % ( 95 % CI = 26.5%-53.3 % ) versus 40.7 % ( 95 % CI = 27.6%-55.0 % ) , respectively , p = 1.0 , at the end of the treatment ( Week 52 ) . Relapse to alcohol occurred in 4 % of subjects ( n = 4 ) during the study . DISCUSSION Treatment with bupropion SR among abstinent alcoholic smokers did not delay relapse or result in improved long-term smoking abstinence INTRODUCTION While many medications can be effective aids to quitting tobacco , real world adherence to smoking cessation medications may render a potentially effective medication ineffective . The present study investigated the role of adherence on treatment outcomes in a bupropion dose-response study among adolescent smokers trying to quit smoking . METHODS Three hundred twelve adolescent boys ( n = 143 ) and girls ( n = 169 ) between the ages of 14 - 17 were enrolled in the study , and were r and omly assigned to use either 300 mg , 150 mg or placebo bupropion to quit smoking . Among the eligibility criterion , participants had to smoke at least six cigarettes per day , be motivated to quit smoking ( self report ) , have an exhaled carbon monoxide level greater than or equal to 10 ppm , and report at least two previous quit attempts . Adherence to medication was determined by both self-report and actual counts of unused medication and empty medication packaging . Smoking status was determined by a combination of self-report and biochemical verification ( breath carbon monoxide and urine cotinine ) . RESULTS Cotinine-confirmed quit rates were significantly higher as a function of high adherence ( 20.69 % ) relative to low adherence ( 0.00 % ) in the 300-mg Bupropion Sustained Release group . Overall adherence in all study conditions in this highly controlled study was high ( 74 % ) , but was significantly lower in non-white participants . CONCLUSIONS Effectiveness of bupropion for adolescent smoking cessation is contingent on achieving high rates of medication adherence , but considerable variations in adherence impacted outcomes . IMPLICATION S Few studies have assessed the safety and efficacy of medications to help adolescent smokers quit , and we conducted one such study assessing bupropion . In this analysis of that original study , we assess the role of adherence in use of medication and quit rates . We found that adherence was related to outcomes , particularly in the 300-mg dose of bupropion Little is known about the impact of alcohol involvement on smoking cessation relapse or possible mechanisms for these associations . We addressed these issues using data from a r and omized clinical trial of two types of framed messages ( gain vs. loss ) in conjunction with open label sustained-release ( SR ) bupropion ( Toll et al. , 2007 ) ( N = 249 ) . Participants were categorized according to whether or not they were diagnosed with a lifetime alcohol use disorder ( AUD ; i.e. , current or past alcohol abuse or past alcohol dependence ) and according to three levels of alcohol use : abstinence , moderate , or hazardous use . Alcohol use categories were established for drinking at baseline , during the 6-week treatment period and through 12 weeks post-quit . There were few significant differences by baseline alcohol use level or AUD history for a series of predictors of smoking cessation failure ( e.g. , depressive symptoms ) . During treatment and follow-up , the probability of any smoking on heavy drinking days was significantly higher than the probability of smoking on moderate drinking or abstinent days . AUD history did not predict smoking cessation relapse in any analysis , nor were any alcohol usexAUD history interactions significant . Moderate alcohol users and , to a lesser extent , abstainers from alcohol at baseline were less likely than hazardous drinkers to have relapsed at 12 weeks post-quit . Based on these findings , it appears that risk of any smoking and of relapse was associated primarily with heavy drinking days and a hazardous pattern of use respectively , rather than with moderate drinking In the current study , we investigated how individual variants in the serotonin promoter gene , previously associated with smoking cessation and linked to anxiety-related personality traits , were associated with individual differences in responsiveness to bupropion and cognitive behavioral therapy ( CBT ) in a clinical population . We hypothesize that subjects with the long allele may be less responsive to treatment . Altogether 61 schizophrenic patients ( 46 M , 15 F ) on stable neuroleptic medication were initially enrolled in a smoking reduction program ( prospect i ve , double-blind , placebo-controlled ) including cognitive behavioral therapy plus placebo or CBT plus bupropion . Additionally , subjects were genotyped for a polymorphism in the serotonin transporter ( SLC6A4 ) . Thirty-two subjects ( 23 M , 9 F ) completed a 14-week course of treatment . While both groups of subjects demonstrated significant reductions in smoking behavior due to CBT , subjects receiving bupropion did not show significant differences in smoking behavior when compared to placebo . In addition , analysis by SPSS repeated measures multivariate showed a significant sex by SLC6A4 genotype interaction on the number of cigarettes smoked . Only male subjects with at least one short promoter region allele ( short/short and short/long combined ) showed a reduction in cigarette consumption as a result of treatment . This study provides preliminary evidence of how polymorphisms in the serotonin transporter can be informative in predicting individual responses to smoking reduction therapy OBJECTIVE Knowledge of smoking change processes may be enhanced by identifying pathways to stable abstinence . We sought to identify latent classes of smokers based on their day-to-day smoking status in the first weeks of a cessation attempt . We examined treatment effects on class membership and compared classes on baseline individual differences and 6-month abstinence rates . METHOD In this secondary analysis of a double-blind r and omized placebo-controlled clinical trial ( N = 1,433 ) of 5 smoking cessation pharmacotherapies ( nicotine patch , nicotine lozenge , bupropion SR , patch and lozenge , or bupropion SR and lozenge ) , we conducted repeated- measures latent class analysis of daily smoking status ( any smoking vs. none ) for the first 27 days of a quit attempt . Treatment and covariate relations with latent class membership were examined . Distal outcome analysis compared confirmed 6-month abstinence rates among the latent classes . RESULTS A 5-class solution was selected . Three-quarters of smokers were in stable smoking or abstinent classes , but 25 % were in classes with unstable abstinence probabilities over time . Active treatment ( compared to placebo ) , and particularly the patch and lozenge combination , promoted early quitting . Latent classes differed in 6-month abstinence rates and on several baseline variables , including nicotine dependence , quitting history , self-efficacy , sleep disturbance , and minority status . CONCLUSIONS Repeated- measures latent class analysis identified latent classes of smoking change patterns affected by treatment , related to known risk factors , and predictive of distal outcomes . Tracking behavior early in a change attempt may identify prognostic patterns of change and facilitate adaptive treatment planning |
12,908 | 28,291,302 | Authors ' conclusions Group‐based psychosocial interventions may have a small effect on measures of depression , but the clinical importance of this is unclear .
More high quality evidence is needed to assess whether group psychosocial intervention improve psychological well‐being in HIV positive adults | Background Being diagnosed with human immunodeficiency virus ( HIV ) , and labelled with a chronic , life‐threatening , and often stigmatizing disease , can impact on a person 's well‐being .
Psychosocial group interventions aim to improve life‐functioning and coping as individuals adjust to the diagnosis .
Objectives To examine the effectiveness of psychosocial group interventions for improving the psychological well‐being of adults living with HIV/AIDS . | OBJECTIVE To examine whether ( a ) Living in the Face of Trauma ( LIFT ) , a group intervention to address coping with HIV and childhood sexual abuse ( CSA ) , significantly reduced traumatic stress over a 1-year follow-up period more than an attention-matched support group comparison intervention ; and ( b ) reductions in avoidant coping over time mediated reductions in traumatic stress . METHOD In a r and omized controlled trial , 247 participants completed measures of traumatic stress and avoidant coping at pre- and post intervention , and at 4- , 8- , and 12-month follow-ups . Latent growth curve modeling examined changes over the 5 time points ; st and ardized path coefficients provide estimates of effects . RESULTS As compared with the support intervention , the coping intervention led to a reduction in traumatic stress over time ( b = -.20 , p < .02 ) . Participants in the coping intervention also reduced their use of avoidant coping strategies more than did participants in the support intervention ( b = -.22 , p < .05 ) . Mediation analyses showed reductions in avoidant coping related to reductions in traumatic stress ( b = 1.45 , p < .001 ) , and the direct effect of the intervention on traumatic stress was no longer significant ( b = .04 , ns ) , suggesting that changes in avoidant coping completely mediated intervention effects on traumatic stress . CONCLUSIONS The LIFT intervention significantly reduced traumatic stress over time , and changes in avoidant coping strategies mediated this effect , suggesting a focus on current stressors and coping skills improvement are important components in addressing traumatic stress for adults living with HIV and CSA Objective This r and omized clinical trial was design ed to compare the effects of a theory-based coping effectiveness training ( CET ) intervention with an active informational control ( HIV-Info ) condition and a waiting-list control ( WLC ) condition on psychological distress and positive mood in HIV-seropositive gay men . Material s and Methods The authors recruited 149 self-identified gay or bisexual men who were 21 to 60 years of age , reported depressed mood , and had CD4 levels of 200 to 700 cells/mm3 . CET and HIV-Info participants attended 10 90-minute group sessions during the 3-month intervention phase and six maintenance sessions over the remainder of the year . Participants were assessed at baseline and at 3 , 6 , and 12 months . Data were collected 1992 to 1994 , before the introduction of HAART . Analyses were based on the 128 participants who completed the 3-month assessment . Results After the 3-month intervention phase , when compared with HIV-Info , CET participants showed significantly greater decreases in perceived stress and burnout , and regression analyses indicated that significant increases in coping self-efficacy mediated the improvements in perceived stress and burnout . Compared with WLC , CET participants also showed significantly greater decreases in anxiety , and regression analyses indicated that significant increases in positive states of mind mediated the improvements in anxiety . Significant treatment group differences for positive morale were maintained at 6 and 12 months . In addition , optimism continued to increase in the CET and HIV-Info treatment groups during the maintenance phase . Conclusions CET can be an effective strategy for managing psychological distress and improving positive psychological states in patients confronting chronic illness 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 To determine whether MBSR groups would help gay men living with HIV improve psychosocial functioning and increase mindfulness compared to treatment-as-usual ( TAU ) . Methods : 117 participants were r and omized 2:1 to MBSR or TAU . No new psychosocial or psychopharmacological interventions were initiated within 2 months of baseline . St and ardized question naires were administered pre- , postintervention and at 6 months . An intent-to-treat analysis found significant benefits of MBSR : at post-intervention and 6 months follow up , MBSR participants had significantly lower avoidance in IES and higher positive affect compared to controls . MBSR participants developed more mindfulness as measured by the Toronto Mindfulness Scale ( TMS ) including both TMS subscales , curiosity and decentering , at 8-week and 6 months . For the sample as a whole , increase in mindfulness was significantly correlated with reduction in avoidance , higher positive affect and improvement in depression at 6 months . MBSR has specific and clinical ly meaningful effects in this population Objectives : To examine the effect of a 15-session coping group intervention compared with a 15-session therapeutic support group intervention among HIV-positive men and women with a history of childhood sexual abuse ( CSA ) on sexual transmission risk behavior . Design : A r and omized controlled behavioral intervention trial with 12-month follow-up . Methods : A diverse sample of 247 HIV-positive men and women with histories of CSA was r and omized to 1 of 2 time-matched group intervention conditions . Sexual behavior was assessed at baseline ; immediately after the intervention ; and at 4- , 8- , and 12-month follow-up periods ( 5 assessment s ) . Changes in frequency of unprotected anal and vaginal intercourse by intervention condition were examined using generalized linear mixed models for all partners , and specifically for HIV-negative or serostatus unknown partners . Results : Participants in the HIV and trauma coping intervention condition decreased their frequency of unprotected sexual intercourse more than participants in the support intervention condition for all partners ( P < 0.001 ; d = 0.38 , 0.32 , and 0.38 at the 4- , 8- , and 12-month follow-up periods , respectively ) and for HIV-negative and serostatus unknown partners ( P < 0.001 ; d = 0.48 , 0.39 , and 0.04 at the 4- , 8- , and 12-month follow-up periods , respectively ) . Conclusion : A group intervention to address coping with HIV and CSA can be effective in reducing transmission risk behavior among HIV-positive men and women with histories of sexual trauma Background : AIDS-related bereavement is a severe life stressor that may be particularly distressing to persons themselves infected with HIV . Increasing evidence suggests that psychological health is associated with disease progression , HIV-related symptoms , and mortality . Purpose : This study assessed change in health-related quality of life among HIV+ persons following a group intervention for coping with AIDS-related loss . Methods : The sample included 235 HIV+ men and women of diverse ethnicities and sexual orientations who had experienced an AIDS-related loss within the previous 2 years . Participants were r and omly assigned to a 12-week cognitive-behavioral bereavement coping group intervention or offered individual psychotherapy upon request . Quality of life was assessed at baseline and 2 weeks after the intervention . Results : Participants in the group intervention demonstrated improvements in general health-related and HIV-specific quality of life , while those in the comparison remained the same or deteriorated . Effect sizes indicated that the majority of change occurred in women . Conclusion : This bereavement group aim ed at improving coping with grief also had a positive impact on health-related quality of life among HIV+ men and women , and suggests that cognitive-behavioral interventions may have a broad impact on both emotional and physical health OBJECTIVE We tested the effects of a 10-week group-based cognitive-behavioral stress management/expressive-supportive therapy intervention ( CBSM+ ) and a time-matched individual psychoeducational condition for 330 women with AIDS reporting moderate to poor baseline quality of life ( QOL ) . The goal of this study was to examine treatment effects on total QOL and 11 QOL domains from baseline to post-intervention follow-up . METHODS Participants were assessed at baseline , r and omized to a treatment condition ( individual psychoeducation condition n=180 , group-based CBSM+ condition n=150 ) , participated in the intervention for 10 weeks and assessed again within 4 weeks following the intervention . QOL was measured using the Medical Outcomes Study -HIV-30 . RESULTS QOL scores increased over the course of both interventions for the total QOL score and three QOL domains : cognitive functioning , health distress and overall health perceptions . While women in the CBSM+ group condition showed a significant improvement in mental health QOL from pre- to post-intervention , women in the individual condition did not change . No changes were observed for energy/fatigue , health transition , single-item overall QOL , pain , physical well-being , role functioning or social functioning in either condition . CONCLUSION Results suggest that group-based CBSM+ and individual psychoeducational interventions are effective at improving certain aspects of QOL and that group-based CBSM+ may be particularly effective at increasing QOL related to mental health in this population of women with AIDS We design ed a r and omized controlled trial of a home based intervention to improve antiretroviral adherence and to assess the impact of depressive symptoms among people living with HIV in Hunan , China . At baseline , 110 subjects reported taking 90 % or less of prescribed medication . At 6 months , when the intervention ended , 56 % of subjects in the control and 87 % of subjects in the experimental group were adherent . This difference was maintained at 12 months . In multivariate analyses , controlling for baseline visual analogue adherence scale , stigma , social support , and Center for Epidemiological Studies Depression scale , the experimental group had a significantly higher proportion of people who were adherent ( p=0.009 ) . The high prevalence of significant depressive symptoms ( 67 % ) at baseline is of concern . It is of particular importance that future studies look at the types of depression likely to be seen in these patients and differentiate early between those likely to benefit from HIV-related support and those who will require additional depression-targeted interventions Numerous herpesvirus infections are associated with clinical ly relevant outcomes as well as an accelerated HIV replication rate and subsequent disease progression . Stress management interventions mayimprovemarkersofcellularimmunecontroloverlatent herpesvirus infections and these changes appear to be mediated by perceptions of increased social support availability . We examined the effects ofagroup-based cognitive behavioral stress management ( CBSM ) intervention on distress , dysphoria , perceived socialsupport , and herpesvirus immunoglobulin G ( IgG ) antibody titers during the 6to 12 months following the intervention . Of those who were initially r and omized , 49 HIV-infected men were followed during the 6-to 12-month period after r and omization to either a 10-week CBSM intervention ( n=31 ) or amodified wait-list control condition ( n = 18 ) . Measures of distress , dysphoria , social support , and blood sample s for herpesvirus Ig Gtiters were taken at baseline , immediately following CBSM and at-6-to 12-month follow-up . Men in CBSM displayed maintenance of previously observed intervention effects on dysphoria , reliable alliance support , and herpesvirus IgG antibody titers ( i.e. , Epstein-Barr virus capsid antigen ; EBV-VCA ) . Intervention-related changes in EBV-VCA were unrelated to changes in lymphocyte subsets ( i.e. , CD4 + , CD8 + , and CD4+:CD8 + ) or changes in measures of dysphoria and social support during the investigation period . Data indicate that HIV-infected men participating in a CBS Mintervention maintain better psychosocial status and immunologic control of latent EBV infection up to 1 year after its conclusion OBJECTIVES Investigate the psychometric characteristics of the coping self-efficacy ( CSE ) scale , a 26-item measure of one 's confidence in performing coping behaviors when faced with life challenges . DESIGN Data came from two r and omized clinical trials ( N1=149 , N2=199 ) evaluating a theory-based Coping Effectiveness Training ( CET ) intervention in reducing psychological distress and increasing positive mood in persons coping with chronic illness . METHODS The 348 participants were HIV-seropositive men with depressed mood who have sex with men . Participants were r and omly assigned to intervention and comparison conditions and assessed pre- and post-intervention . Outcome variables included the CSE scale , ways of coping , and measures of social support and psychological distress and well-being . RESULTS Exploratory ( EFA ) and confirmatory factor analyses ( CFA ) revealed a 13-item reduced form of the CSE scale with three factors : Use problem-focused coping ( 6 items , alpha=.91 ) , stop unpleasant emotions and thoughts ( 4 items , alpha=.91 ) , and get support from friends and family ( 3 items , alpha=.80 ) . Internal consistency and test-retest reliability are strong for all three factors . Concurrent validity analyses showed these factors assess self-efficacy for different types of coping . Predictive validity analyses showed that residualized change scores in using problem- and emotion-focused coping skills were predictive of reduced psychological distress and increased psychological well-being over time . CONCLUSIONS The CSE scale provides a measure of a person 's perceived ability to cope effectively with life challenges , as well as a way to assess changes in CSE over time in intervention research This clinical trial evaluated a modified therapeutic community aftercare ( MTC-A ) program for a population triply diagnosed with HIV/AIDS , a substance use disorder , and a mental disorder . After six months of MTC residential treatment ( MTC-R ) , subjects were r and omly assigned to MTC-A ( n=42 ) or to st and ard aftercare ( C ; n=34 ) . Follow-up interviews at six and 12 months assessed eight outcome domains and adherence to prescribed HIV medication . A propensity model was used to re-balance the retrieved sample . At the six-month follow-up , High stratum MTC-A clients ( those with greater psychological functioning and stable physical health at baseline ) had greater improvement overall and for substance use and mental health than C clients in the same stratum . In contrast , C clients in the Low/Medium stratum ( those with poorer psychological functioning and improved physical health ) had more favorable outcomes overall and for substance use than their MTC-A counterparts ; however , this stratum was not re-balanced effectively . Differences in HIV medication adherence were not detected . Clients with greater psychological functioning and stable health at treatment entry benefit more from the MTC-A program . In view of the potentially progressive nature of HIV , measuring physical and mental health during treatment and controlling for changes could be important in future research Background : Stress management interventions for HIV-positive persons have been design ed to enhance coping skills and encourage health-promoting behaviors with the hope of decreasing distress and slowing disease progression . Purpose : We examined the efficacy of a cognitive behavioral stress management ( CBSM ) intervention in combination with medication adherence training ( MAT ) in 130 gay and bisexual men living with HIV infection . Methods : Participants were r and omized to either a 10-week CBSM+MAT intervention ( n = 76 ) or a MAT-only condition ( n = 54 ) . Measures of self-reported adherence , active cognitive coping ( i.e. , acceptance and positive reinterpretation ) , avoidant coping ( i.e. , denial and behavioral disengagement ) , and depressed mood were examined over the 10-week intervention period . Results : Men in CBSM+MAT reported reductions in depressed mood and denial coping during the 10-week intervention period , but no changes in active cognitive coping or self-reported adherence were observed . Using path analysis , greater reliance on denial coping at baseline was associated with decreased depressed mood at 10 weeks . We also determined that CBSM+MAT may decrease depressed mood by reducing reliance on denial coping over the 10-week intervention period . Conclusions : Although denial may be an effective means of distress reduction in the short term , reliance on this coping strategy may result in a decreased capacity to effectively manage a variety of disease-related stressors in the long term . CBSM+MAT addresses this potentially detrimental pattern by teaching stress reduction skills that may decrease depressed mood via reduced reliance on denial coping The authors of this study evaluated a structured 10-session psychosocial support group intervention for newly HIV-diagnosed pregnant South African women . Participants were expected to display increases in HIV disclosure , self-esteem , active coping and positive social support , and decreases in depression , avoidant coping , and negative social support . Three hundred sixty-one pregnant HIV-infected women were recruited from four antenatal clinics in Tshwane townships from April 2005 to September 2006 . Using a quasi-experimental design , assessment s were conducted at baseline and two and eight months post-intervention . A series of r and om effects regression analyses were conducted , with the three assessment points treated as a r and om effect of time . At both follow-ups , the rate of disclosure in the intervention group was significantly higher than that of the comparison group ( p < 0.001 ) . Compared to the comparison group at the first follow-up , the intervention group displayed higher levels of active coping ( t = 2.68 , p < 0.05 ) and lower levels of avoidant coping ( t = −2.02 , p < 0.05 ) , and those who attended at least half of the intervention sessions exhibited improved self-esteem ( t = 2.11 , p < 0.05 ) . Group interventions tailored for newly HIV positive pregnant women , implemented in re source -limited setting s , may accelerate the process of adjusting to one 's HIV status , but may not have sustainable benefits over time Background People who are HIV-positive now live longer when they have contracted AIDS , and nursing interventions can help improve their quality of life . Objectives To test the effects of an intervention based on developing cognitive coping skills as compared to one focused on facilitating the expression of emotions . Both interventions were intended to help regulate emotional response to an exacerbation of HIV-related symptoms . Method In a r and omized , controlled trial , 90 hospitalized HIV-positive men were r and omly assigned to one of three groups : cognitive , expression , or control . The intervention was administered on three consecutive days in 20–30 minute sessions . Preintervention and postintervention data were gathered on mood , distress , and anxiety . Results Both interventions produced a beneficial effect on negative affect ( cognitive group p = .002 , expression group p = .011 ) , and immediately following the first daily session ( p = .001 ) . No change in positive affect was produced by either intervention . Paired t tests indicated a decrease in distress ( p = .039 ) , specifically , of intrusive ideation ( p = .03 ) , for the cognitive group , which also experienced a decrease in anxiety from immediately before to immediately after each session . Conversely , the expression group experienced an increase in anxiety ( p = .018 ) . Discussion The cognitive coping skills nursing intervention was effective in helping to regulate HIV-positive persons ’ emotional responses to advanced disease . This nursing intervention is feasible for use by skilled practitioners providing daily care Background There is evidence that various meditation practice s reduce distress , but little is known about the mechanisms of frequently repeating a mantram — a spiritual word or phrase — on distress reduction . Mantram repetition is the portable practice of focusing attention frequently on a mantram throughout the day without a specific time , place , or posture . Purpose We examined the hypothesis of whether increases in positive re appraisal coping or distancing coping mediated the sustained decreases in anger found following a group-based mantram intervention that was design ed to train attention and promote awareness of internal experiences . Method A secondary analysis was performed on data collected from a r and omized controlled trial that compared a group-based mantram intervention ( n = 46 ) to an attention-matched control ( n = 47 ) in a community sample of human immunodeficiency virus-positive adults . Positive re appraisal and distancing coping were explored as potential mediators of anger reduction . Results Participants in the mantram intervention reported significant increases in positive re appraisal coping over the 5-week intervention period , whereas the control group reported decreases . Increases in positive re appraisal coping during the 5-week intervention period appear to mediate the effect of mantram on decreased anger at 22-week follow-up . Conclusions Findings suggest that a group-based mantram intervention may reduce anger by enhancing positive re appraisal coping AIMS Dual epidemics of human immunodeficiency virus ( HIV ) and alcohol use disorders , and a dearth of professional re sources for behavioral treatment in sub-Saharan Africa , suggest the need for development of culturally relevant and feasible interventions . The purpose of this study was to test the preliminary efficacy of a culturally adapted six-session gender-stratified group cognitive-behavioral therapy ( CBT ) intervention delivered by paraprofessionals to reduce alcohol use among HIV-infected out- patients in Eldoret , Kenya . DESIGN R and omized clinical trial comparing CBT against a usual care assessment -only control . SETTING A large HIV out-patient clinic in Eldoret , Kenya , part of the Academic Model for Providing Access to Healthcare collaboration . PARTICIPANTS Seventy-five HIV-infected out- patients who were antiretroviral (ARV)-initiated or ARV-eligible and who reported hazardous or binge drinking . MEASUREMENTS Percentage of drinking days ( PDD ) and mean drinks per drinking days ( DDD ) measured continuously using the Time line Follow back method . FINDINGS There were 299 ineligible and 102 eligible out- patients with 12 refusals . Effect sizes of the change in alcohol use since baseline between the two conditions at the 30-day follow-up were large [ d=0.95 , P=0.0002 , mean difference=24.93 , 95 % confidence interval ( CI ) : 12.43 , 37.43 PDD ; d=0.76 , P=0.002 , mean difference=2.88 , 95 % CI : 1.05 , 4.70 DDD ] . R and omized participants attended 93 % of the six CBT sessions offered . Reported alcohol abstinence at the 90-day follow-up was 69 % ( CBT ) and 38 % ( usual care ) . Paraprofessional counselors achieved independent ratings of adherence and competence equivalent to college-educated therapists in the United States . Treatment effect sizes were comparable to alcohol intervention studies conducted in the United States . CONCLUSIONS Cognitive-behavioral therapy can be adapted successfully to group paraprofessional delivery in Kenya and may be effective in reducing alcohol use among HIV-infected Kenyan out- patients Objective : Human Immunodeficiency Virus (HIV)–positive individuals treated with highly active antiretroviral therapy ( HAART ) may experience psychological burdens and negative mood states , which could impair their ability to derive maximum benefits from their medical treatment . We tested whether a cognitive behavioral stress management ( CBSM ) intervention in combination with antiretroviral medication adherence training ( MAT ) from a clinical pharmacist influences HIV viral load more than MAT alone . Methods : HIV-positive men who have sex with men were r and omized to either a 10-week CBSM + MAT intervention ( n = 76 ) or a MAT-Only condition ( n = 54 ) . Data were collected at baseline immediately following the 10-week intervention period , at 9 months postr and omization , and at 15 months postr and omization . Results : We found no differences in HIV viral load among the 130 men r and omized . However , in the 101 men with detectable viral load at baseline , those r and omized to CBSM + MAT ( n = 61 ) displayed reductions of 0.56 log10 units in HIV viral load over a 15-month period after controlling for medication adherence . Men in the MAT-Only condition ( n = 40 ) showed no change . Decreases in depressed mood during the intervention period explained the effect of CBSM + MAT on HIV viral load reduction over the 15 months . Conclusions : A time-limited CBSM + MAT intervention that modulates depressed mood may enhance the effects of HAART on suppression of HIV viral load in HIV+ men with detectable plasma levels . AIDS = acquired immunodeficiency syndrome ; ACTG = Adherence to Combination Therapy Guide ; BDI = Beck Depression Inventory ; CBSM = cognitive behavioral stress management ; CET = coping effectiveness training ; EDTA = ethylenediaminetetraacetic acid ; HAART = highly active antiretroviral therapy ; HIV = human immunodeficiency virus ; MAT = medication adherence training ; MEMS = medication event monitoring system ; POMS = Profile of Mood States Child sexual abuse ( CSA ) is associated with HIV risk behaviors [ Bensley , L. , Van Eenwyk , J. , and Simmons , K. W. , 2003 . ] and more prevalent among women living with HIV than in the general population [ Koenig , L. J. , and Clark , H. , 2004 ] . This r and omized Phase ~ I clinical trial tested the impact of a culturally congruent psychoeducational intervention design ed to reduce sexual risks and increase HIV medication adherence for HIV-positive women with CSA histories . An ethnically diverse sample of 147 women were r and omized to two conditions : an 11-session Enhanced Sexual Health Intervention ( ESHI ) or an attention control . Results based on “ intent to treat ’ ’ analysesof pre – post changes are reported here . Additional analyses explored whether theobserved effects might depend on “ intervention dose , ’ ’ i.e. , number of sessions attended . Women in the ESHI condition reported greater sexual risk reduction than women in the control condition . Although there were no differences between women in the ESHI and control groups on medication adherence , women in the ESHI condition who attended 8 or more sessions reported greater medication adherence at posttest than control women . The findings provide initial support for this culturally and gender-congruent psychoeducational intervention for HIV-positive women with CSA , and highlight the importance of addressing the effects of CSA on sexual risk reduction and medicationadherence in preventive interventions for women This prospect i ve multisite Phase III clinical trial ( Miami , New York , New Jersey ) investigated the long-term ( one year ) effects of a 10-week group cognitive-behavioral stress management/expressive supportive therapy ( CBSM+ ) intervention on disadvantaged minority women living with AIDS . The CBSM+ intervention consisted of 10-weekly group session of stress management , cognitive-behavioral skill training , relaxation techniques and expressive-supportive therapeutic strategies . The primary study outcome was self-reported depression scores as measured by the BDI . The CBSM+ Group intervention significantly decreased depression scores on the BDI for women following the intervention and maintained the decreased level at one-year follow-up Objectives We studied the incidence and prevalence of , and co-factors for depression in the Swiss HIV Cohort Study . Methods Depression-specific items were introduced in 2010 and prospect ively collected at semiannual cohort visits . Clinical , laboratory and behavioral co-factors of incident depression among participants free of depression at the first two visits in 2010 or thereafter were analyzed with Poisson regression . Cumulative prevalence of depression at the last visit was analyzed with logistic regression . Results Among 4,422 participants without a history of psychiatric disorders or depression at baseline , 360 developed depression during 9,348 person-years ( PY ) of follow-up , result ing in an incidence rate of 3.9 per 100 PY ( 95 % confidence interval ( CI ) 3.5–4.3 ) . Cumulative prevalence of depression during follow-up was recorded for 1,937/6,756 ( 28.7 % ) participants . Incidence and cumulative prevalence were higher in injection drug users ( IDU ) and women . Older age , preserved work ability and higher physical activity were associated with less depression episodes . Mortality ( 0.96 per 100 PY , 95 % CI 0.83–1.11 ) based upon 193 deaths over 20,102 PY was higher among male IDU ( 2.34 , 1.78–3.09 ) , female IDU ( 2.33 , 1.59–3.39 ) and white heterosexual men ( 1.32 , 0.94–1.84 ) compared to white heterosexual women and homosexual men ( 0.53 , 0.29–0.95 ; and 0.71 , 0.55–0.92 ) . Compared to participants free of depression , mortality was slightly elevated among participants with a history of depression ( 1.17 , 0.94–1.45 vs. 0.86 , 0.71–1.03 , P = 0.033 ) . Suicides ( n = 18 ) did not differ between HIV transmission groups ( P = 0.50 ) , but were more frequent among participants with a prior diagnosis of depression ( 0.18 per 100 PY , 95%CI 0.10–0.31 ; vs. 0.04 , 0.02–0.10 ; P = 0.003 ) . Conclusions Depression is a frequent co-morbidity among HIV-infected persons , and thus an important focus of care ABSTRACT A r and omized , controlled , clinical trial was conducted to examine the impact of a semistructured , 10-week , once weekly , 90-min/session bereavement support group intervention on immunological , neuroendocrine , and clinical health status in human immunodeficiency virus type 1-seropositive ( HIV-1 + ) and HIV-1-seronegative ( HIV-1− ) homosexual men , compared to a st and ard of care control condition . A total of 119 homosexual men ( 74 HIV-1 + and 45 HIV-1− ) were assessed at baseline , 10 weeks , and 6 months follow-up . At the 6-month follow-up assessment , the intervention groups exhibited significant beneficial effects compared to controls on changes in CD4 cell , total T-lymphocyte , and total lymphocyte counts , when baseline levels , antiretroviral medication use , CDC stage of disease , and other potentially confounding factors were accounted for . There was no statistically significant effect on the CD4/CD8 ratio or on the CD8 cell count . The effect on CD4 cell count was associated with group attendance and with changes in plasma cortisol level . Plasma cortisol levels decreased significantly among intervention subjects , compared to controls . A significantly reduced number of health care visits over the 6-month follow-up period among the intervention subjects supported the clinical relevance of the immunological changes observed for both HIV-1 + and HIV-1−individuals . These results indicate that behavioral interventions may have salutary immunological and clinical health effects following bereavement among HIV-1-infected individuals . The effect in HIV-1− individuals suggests that this bereavement support group intervention might have similar salutary effects in the general population . Potential effects of such interventions on clinical HIV disease progression are of interest and should be studied Stress is implicated in the pathogenesis and progression of HIV . The Transcendental Meditation ( TM ) is a behavioral stress reduction program that incorporates mind – body approach , and has demonstrated effectiveness in improving outcomes via stress reduction . We evaluated the feasibility of implementing TM and its effects on outcomes in persons with HIV . In this community-based single blinded Phase-I , r and omized controlled trial , outcomes ( psychological and physiological stress , immune activation , generic and HIV-specific health-related quality of life , depression and quality of well-being ) were assessed at baseline and at six months , and were compared using parametric and nonparametric tests . Twenty-two persons with HIV were equally r and omized to TM intervention or healthy eating ( HE ) education control group . Retention was 100 % in TM group and 91 % in HE control group . The TM group exhibited significant improvement in vitality . Significant between group differences were observed for generic and HIV-specific health-related quality of life . Small sample size may possibly limit the ability to observe significant differences in some outcomes . TM stress reduction intervention in community dwelling adults with HIV is viable and can enhance health-related quality of life . Further research with large sample and longer follow-up is needed to vali date our results This study examined the longitudinal effects of coping on outcome one year following completion of a r and omized , controlled trial of a group coping intervention for AIDS-related bereavement . Bereaved HIV-positive participants ( N = 267 ) were administered measures of grief , psychiatric distress , quality of life , and coping at baseline , post-intervention , and at 4- , 8- , and 12-month follow-ups . Coping strategies directly impacted all outcome variables for both study conditions . Additionally , the coping intervention moderated the relationship between avoidant coping and the longitudinal course of grief and psychiatric distress , result ing in greater reductions in grief and distress for intervention participants after accounting for avoidant coping strategies Background Pregnant women living with HIV ( WLH ) face daily challenges maintaining their own and their babies ' health and mental health . St and ard Prevention of Maternal to Child Transmission ( PMTCT ) programs are not design ed to address these challenges . Methods / Design As part of a cluster r and omized controlled trial , WLH are invited to attend four antenatal and four postnatal small group sessions led by a peer WLH ( a Peer Mentor ) . The WLH and their babies are assessed during pregnancy and at one week , six months , and twelve months post-birth . Mobile phones are used to collect routine information , complete question naires and remain in contact with participants over time . Pregnant WLH ( N = 1200 ) are r and omly assigned by clinic ( N = 8 clinics ) to an intervention program , called Masihambisane ( n = 4 clinics , n = 600 WLH ) or a st and ard care PMTCT control condition ( n = 4 clinics ; n = 600 WLH ) . Discussion Data collection with cellular phones are innovative and effective in low-re source setting s. St and ard PMTCT programs are not design ed to address the daily challenges faced by WLH ; Peer Mentors may be useful in supporting WLH to cope with these challenges . Trial registration Clinical Trials.gov registration # UNLABELLED Mindfulness meditation training has stress reduction benefits in various patient population s , but its effects on biological markers of HIV-1 progression are unknown . The present study tested the efficacy of an 8-week Mindfulness-based stress reduction ( MBSR ) meditation program compared to a 1-day control seminar on CD4 + T lymphocyte counts in stressed HIV infected adults . A single-blind r and omized controlled trial was conducted with enrollment and follow-up occurring between November 2005 and December 2007 . A diverse community sample of 48 HIV-1 infected adults was r and omized and entered treatment in either an 8-week MBSR or a 1-day control stress reduction education seminar . The primary outcome was circulating counts of CD4 + T lymphocytes . Participants in the 1-day control seminar showed declines in CD4 + T lymphocyte counts whereas counts among participants in the 8-week MBSR program were unchanged from baseline to post-intervention ( time x treatment condition interaction , p=.02 ) . This effect was independent of antiretroviral ( ARV ) medication use . Additional analyses indicated that treatment adherence to the mindfulness meditation program , as measured by class attendance , mediated the effects of mindfulness meditation training on buffering CD4 + T lymphocyte declines . These findings provide an initial indication that mindfulness meditation training can buffer CD4 + T lymphocyte declines in HIV-1 infected adults . CLINICAL TRIALS REGISTRATION clinical trials.gov , Identifier : NCT00600561 Abstract Symptom management for persons living with HIV/AIDS is an extremely important component of care management . The importance of pharmacologic interventions for management of symptoms is well recognized , and non-pharmacologic strategies such as art therapy are gaining interest in lay and professional communities . The aim of this research project was to test the feasibility and effectiveness of art therapy for relief of symptoms experienced by people living with HIV/AIDS . In this r and omized clinical trial of art therapy , the primary objective was to assess change in physical and psychological symptoms . Participants were recruited from a large urban hospital 's inpatient population and outpatient HIV clinic . Seventy-nine people with a diagnosis of HIV infection provided socio-demographic information , participated in either a one-hour art therapy session or viewed a videotape about art therapy , and completed pre- and posttest measures of psychological and physical symptoms . Two separate analysis of covariance models were used to identify if the treatment condition influenced psychological and physical symptoms , after adjusting for pretest score , age , gender , and race/ethnicity . The analyses showed that physical symptom mean scores were better for those who participated in the art therapy compared to those who viewed the videotape , and this difference between conditions was statistically significant ( p<0.05 ) . Thus , the study demonstrated the potential benefits of one session of art therapy in relation to symptoms associated with HIV/AIDS Abstract The Making Our Mothers Stronger ( MOMS ) Project is a r and omized controlled behavioral trial , comparing a stress-reduction and social support intervention ( Healthy MOMS ) to a parenting skills intervention ( Parenting Skills for MOMS ) for mothers living with HIV . Outcomes include maternal mental and physical health , parenting behaviors , and children 's behavior . To ensure that these interventions were tailored to the needs of HIV + mothers , extensive formative work was conducted with members of the intended audience and relevant service providers . Findings from focus groups and semi-structured interviews highlighted the need for Healthy MOMS to : ( 1 ) include appropriate approaches to group discussion and problem solving ; ( 2 ) address the stressors of being both a parent and a woman living with HIV ; and ( 3 ) enhance social support . Six weekly group sessions focused on topics including coping with stress and anxiety ; enhancing nutrition , exercise , and sexual health ; improving medical adherence ; improving communication with health care providers ; and communicating health needs to family , friends , and co-workers . Initial anecdotal responses from participants suggest that the Healthy MOMS intervention addresses several salient issues for the growing population of HIV + mothers who can benefit from long-term support in adapting to this chronic disease The purpose of this study was to investigate the effect of a symptom management program on self-care of medication side effects among AIDS/HIV-positive patients . Sixty-seven patients from a sexually transmitted disease control center , a medical center , and a Catholic AIDS support group in Taipei were r and omly assigned to three groups : one-on-one teaching , group teaching , and a control group . All subjects in each teaching group attended a 60- or 90-minute program on highly active antiretroviral therapy ( HAART ) side effect self-care education and skill training once per week for 3 weeks ; subjects also underwent counseling by telephone . A medication side effect self-care knowledge question naire , Rosenberg 's Self-Esteem Scale ( RSES ) , and unscheduled hospital visits were used to evaluate the effectiveness of the symptom management program . The results revealed there were significant differences in mean difference of knowledge and unscheduled hospital visits between baseline and post-testing at 3 months for symptom management in the two groups . The mean difference of the self-esteem scale was not significant between the two groups . In summary , the symptom management program effectively increased the ability of AIDS/HIV-positive patients to self-care for medication side effects . We recommend that this program be applied in the clinical nursing practice This study evaluated an intervention to facilitate adaptive coping by persons living with HIV ( PLWH ) , with the participation of their cohabiting partners as a dimension of the intervention . An experimental design with r and omization was used , and 84 PLWH and their partners were recruited . The intervention was based on a psychosocial educational model that incorporated four 2-hour sessions focused on communication , stress appraisal , adaptive coping strategies , and building social support . Both members of the dyad were included in each session . The comparison control included four supportive phone calls to the PLWH alone . Data were collected from both the PLWH and their partner in each of the two groups at baseline , immediately following the intervention , and 3 months and 6 months posttreatment . Data were analyzed using repeated measures analysis of variance , with change scores from the partner data being covariates . Results indicated that the design was a feasible model , which demonstrated potential for the management of stress and possibly problems such as adherence in PLWH . A manual was developed as a part of this intervention and is currently available Abstract Project HEART , an acronym for Helping Enhance Adherence to Retroviral Therapy , was a prospect i ve , controlled study to develop , implement , and evaluate a clinic-based behavioural intervention to prevent adherence failure among HIV-infected adults beginning their first highly active antiretroviral therapy ( HAART ) regimen ( N = 227 ) . In this paper , we describe the conceptualisation of the Project HEART adherence intervention , characteristics of the participants , and lessons learned implementing HEART in an inner-city clinic setting . A multi-component intervention , HEART combined enhanced education , reminders , adherence feedback , social support and adherence-focused problem solving in an integrated manner to address common cognitive , motivational , and social barriers to adherence . Unique components of the intervention included use of participant-identified adherence support partners and a st and ardized adherence barriers assessment to develop and implement individualised adherence plans . Lessons learned regarding the feasibility of using participant-identified support partners were as follows . Few participants eligible for the study had trouble identifying a support partner . Over 90 % of support partners attended at least one intervention visit . Support partners were most available and amenable to participate early in the initiation of therapy . Participants ’ experiences as the ‘ supported ’ partner were generally positive . Though many participants faced barriers not easily addressed by this intervention ( for example , housing instability ) , formally integrating support partners into the intervention helped to address many other common adherence barriers . Family and friends are an under-utilised re source in HIV medication adherence . Enlisting the help of support partners is a practical and economical approach to adherence counselling Accurate HCV knowledge is lacking among high-risk groups , including people with HIV/AIDS ( PLWHA ) . Liver disease primarily due to HCV has emerged as a serious cause of mortality among PLWHA . We used an Interrupted Time Series design to evaluate a social-ecologically based intervention for PLWHA , where an infectious disease clinic serving a six-county intervention area was monitored before ( 7 months ) and after ( 17 months ) intervention onset . The intervention included education of PLWHA and medical providers , HIV/HCV support groups , and adaptation of the patient chart top sheet to include HCV test information . Clinic-level outcomes were assessed prospect ively every other week for 2 years by interviewing patients ( n = 259 ) with clinic appointments on assessment days . Abrupt , gradual and delayed intervention effects were tested . Weighted regression analyses showed higher average HCV knowledge and a higher prevalence of patients reporting HCV discussion with their medical providers after intervention onset . A delayed effect was found for HCV awareness , and a gradually increasing effect was found for knowing one ’s HCV status . Other communities may consider adopting this intervention . Additional HCV interventions for PLWHA with HIV are needed OBJECTIVES Previous research among HIV-infected individuals suggests that spiritual well-being is inversely related to psychological distress and rates of disease progression . Use of a mantram , a spiritual word or phrase repeated frequently and silently throughout the day , has been associated with decreased psychological distress and increased spiritual well-being . This study compared the effects of 2 interventions -a spiritually-based mantram intervention versus an attention-matched control group-on faith/assurance and average salivary cortisol levels among HIV-infected individuals . METHODS Using a r and omized design , HIV-infected adults were assigned to the intervention ( n = 36 ) or control condition ( n = 35 ) . Faith scores and saliva ( collected at 7 a.m. , 11 a.m. , 4 p.m. , and 9 p.m. ) were assessed at preintervention , postintervention , and 5-week follow-up . Path analyses tested competing models that specify both concurrent and sequential relationships between faith and average daily cortisol levels while comparing groups . RESULTS Faith levels increased among mantram participants from pre- to postintervention . Greater faith at preintervention was significantly associated with lower average cortisol at postintervention in the mantram group but not in the controls . The associations between faith at postintervention and cortisol levels at 5-week follow-up were significant among both groups but weaker than the pre- to postintervention association identified in the mantram group . CONCLUSIONS These results suggest the presence of lagged or antecedent consequent relationships between faith and cortisol , which may be enhanced by mantram use . Decreased cortisol could potentially benefit immune functioning among HIV-infected individuals Care and support should play a critical role in assisting people who are HIV-positive to underst and the need for prevention and to enable them to protect others . Differences in sexual risk reduction among 154 newly diagnosed HIV-positive individuals from semi-urban Tanzania were examined using a r and omized control design , which assigned a control group to regular health services and an experimental group to enhanced care and support . Data were collected at baseline , three months and six months on self-reported sexual risk behaviours , disclosure of serostatus , reproductive health and psychosocial support . Over the six-month period , significant risk reduction occurred among both groups , with most of the behaviour change occurring during the first three months , e.g. 86 respondents ( 56 % ) reported condom use at last intercourse at 3 months compared with 24(16 % ) at baseline ( p = 0.05 ) . Extra care and support did not lead to increased risk reduction among the experimental group . The study population as a whole significantly changed their behaviour , suggesting that in the short term , learning one is HIV-positive has an impact on risk reduction The objective of the study was to assess the effectiveness of group counseling , using a problem-solving therapy approach , on reducing depressive symptoms and increasing prenatal disclosure rates of HIV status among HIV-positive pregnant women living in Dar es Salaam , Tanzania . A r and omized controlled trial was performed comparing a six-week structured nurse – midwife facilitated psychosocial support group with the st and ard of care . Sixty percent of women in the intervention group were depressed post-intervention , versus 73 % in the control group [ Relative Risk ( RR ) = 0.82 , 95 % confidence interval ( CI ) : 0.67–1.01 , p=0.066 ] . HIV disclosure rates did not differ across the two study arms . However , among those women who disclosed , there was a significantly higher level of overall personal satisfaction with the response to disclosure from family and friends among women in the treatment ( 88 % ) compared to the control group ( 62 % ; p=0.004 ) . The results indicate reductions in the level of depressive symptoms comparable with major depressive disorder ( MDD ) for HIV-positive pregnant women participating in a group counseling intervention . Although the psychosocial group counseling did not significantly increase disclosure rates , an improvement in the level of personal satisfaction result ing from disclosure was associated with the intervention . This suggests that the counseling sessions have likely reduced the burden of depression and helped clients better manage partner reactions to disclosure . Public agencies and non-governmental organizations working in Tanzania and similar setting s should consider offering structured psychosocial support groups to HIV-positive pregnant women to prevent poor mental health outcomes , promote early childhood development , and potentially impact HIV-related disease outcomes in the long term Objective : To assess the efficacy of a couple-based intervention to improve medication-taking behavior in a clinic population with demonstrated adherence problems . Design : A r and omized controlled trial ( SMART Couples Study ) conducted between August 2000 and January 2004 . Setting : Two HIV/AIDS outpatient clinics in New York City . Participants : Heterosexual and homosexual HIV-serodiscordant couples ( n = 215 ) in which the HIV-seropositive partner had < 80 % adherence at baseline . The sample was predominantly lower-income racial/ethnic minorities . Intervention : Participants were r and omly assigned to a four-session couple-focused adherence intervention or usual care . The intervention consisted of education about treatment and adherence , identifying adherence barriers , developing communication and problem-solving strategies , optimizing partner support , and building confidence for optimal adherence . Outcome measures : Medication adherence at week 8 ( 2 weeks after the intervention ) compared with baseline , assessed with a Medication Event Monitoring System cap . Results : Intervention participants showed higher mean medication adherence at post-intervention when compared with controls whether adherence was defined as proportion of prescribed doses taken ( 76 % versus 60 % ) or doses taken within specified time parameters ( 58 % versus 35 % ) . Also , participants in the intervention arm were significantly more likely to achieve high levels of adherence ( > 80 % , > 90 % , or > 95 % ) when compared with controls . However , in most cases , effects diminished with time , as seen at follow-up at 3 and 6 months . Conclusion : The SMART Couples program significantly improved medication adherence over usual care , although the level of improved adherence , for many participants , was still suboptimal and the effect was attenuated over time Sexual risk behavior interventions in sub-Saharan Africa focus predominantly on individual and couples counseling . This cognitive-behavioral group intervention was adapted from an urban US context to urban Zambia . Preliminary data analyses assessed the influence of partner participation on sexual risk behavior among HIV-positive Zambian women . Female participants ( n=180 ) attended four group intervention sessions and received sexual behavior skill training and male and female condoms ; male partners ( n=152 ) were r and omly assigned to high-or low-intensity genderconcordant group intervention sessions . Sexual risk behavior , strategies , attitudes , and knowledge were assessed at baseline , 6 , and 12 months . At baseline , 19 % of males reported using alcohol before sex , 10 % reported using alcohol to cope , and negative coping was associated with sexual risk behavior . In contrast , 1 % of women reported using alcohol before sex , and 15 % used alcohol as an HIV-coping strategy . Consistent barrier use was reported by 48 % of women and 74 % of men . After intervention , female high intensity participants reported higher rates of condom use ( F=5.68 , P=.02 ) , more positive condom attitudes , safer sex intentions , and less alcohol use . These findings highlight the influence of male partners in implementation of effective risk reduction interventions The purpose of this study was to examine the mechanisms responsible for the beneficial psychological effects of a coping-focused group intervention for HIV-positive individuals who had lost loved ones to AIDS . Data from 235 HIV-positive men and women enrolled in a r and omized controlled clinical trial testing a coping-focused group intervention were analyzed using a multiple-indicator-multiple-cause ( MIMIC ) structural equation model . Results revealed that the effects of the intervention on decreases in depression and grief were mediated by decreases in avoidant coping . Specifically , participants in the intervention condition decreased their use of avoidant coping . Decreases in avoidant coping , in turn , were related to decreased depression and grief . The results of this study help to vali date the use of coping-focused interventions for HIV-positive bereaved individuals The study delineated depressive symptoms and modeled emotional distress in persons living with HIV disease in nonmetropolitan areas of 13 U.S. states . Participants ( N=329 ) were enrolled in a r and omized clinical trial of a telephone-delivered , coping improvement group intervention , and 60 % reported moderate or severe levels of depressive symptomatology on the Beck Depression Inventory . Structural equation modeling indicated that participants who experienced more severe HIV symptomatology , received less social support , and engaged in more avoidant coping also experienced more emotional distress ( a latent construct comprising depressive symptoms and emotional well-being ) . Greater HIV-related stigma and rejection by family led to more emotional distress , with social support and avoidant coping mediating almost entirely the effects of the former 2 variables . The model accounted for 72 % of the variance in emotional distress in nonmetropolitan persons living with HIV disease OBJECTIVE Compare the efficacy of a multicomponent social support intervention to st and ard-of-care counseling on medication adherence among HIV-infected patients initiating antiretroviral therapy . DESIGN R and omized controlled trial . Generalized estimating equations tested for differences in the percentage of participants achieving 90 % adherence . MAIN OUTCOME MEASURES Pill-taking , electronically monitored over 6 consecutive months ; plasma viral load ( VL ) , assessed at 3 and 6 months following initiation of therapy . RESULTS Of 226 participants who were r and omized and began the trial , 87 ( 38 % ) were lost to the study by 6 months . The proportion of adherent participants declined steadily over time , with no time by group interaction . Sustained adherence was associated with increased odds of achieving an undetectable VL ( OR=1.78 ; 95 % CI=1.01 , 3.13 ) . In intention-to-treat analyses , a larger proportion of the intervention group than the control group was adherent ( 40.15 % vs. 27.59 % , p=.02 ) and achieved an undetectable VL p=.04 ) . However , the majority of participants who remained on study experienced some reduction in VL ( > or=1-log drop or undetectable ) , regardless of experimental condition . CONCLUSION The multicomponent social support intervention significantly improved medication adherence over st and ard-of-care counseling ; evidence for improved virologic outcomes was inconsistent . Early discontinuation of care and treatment may be a greater threat to the health of HIV patients than imperfect medication-taking A pretest-posttest , repeated- measures design was used to evaluate the effects of two stress management interventions on a battery of outcomes derived from a psychoneuroimmunological ( PNI ) framework . The effects of cognitive-behavioral relaxation training groups ( CBSM ) and social support groups ( SSG ) were compared with a WAIT-listed control group on the outcomes of psychosocial functioning , quality of life , neuroendocrine mediation , and somatic health . Participants were 148 individuals ( 119 men , 29 women ) , diagnosed with HIV disease ; 112 ( 76 % ) completing the study groups . Using analysis of covariance , the CBSM group was found to have significantly higher postintervention emotional well-being and total quality -of-life scores than did either the SSG or WAIT groups . SSG participants had significantly lower social/family well-being scores immediately postintervention and lower social support scores after 6 months . The findings point to a pressing need for further , well-controlled research with these common intervention modalities CONTEXT Advances in antiretroviral therapy ( ART ) for HIV offer life-extending benefit ; however , the side effects associated with ART use negatively impact quality of life and medication adherence among people living with HIV . OBJECTIVES This study tested the efficacy of Mindfulness-Based Stress Reduction ( MBSR ) for reducing ART symptoms and bother/distress related to ART side effects . Secondary aims were to test the impact of MBSR on medication adherence and psychological functioning . METHODS Seventy-six people living with HIV who were actively taking ART and reported distress from ART-related side effects were r and omly assigned to an MBSR program or a wait-list control ( WLC ) st and ard care condition . We measured side effects , ART adherence , perceived stress , depression , positive and negative affect , and mindfulness at three time points : baseline , three-month follow-up , and six-month follow-up . Side effects and related distress were assessed separately from other symptoms . RESULTS Compared with a WLC , participants in the MBSR condition experienced a reduction in the frequency of symptoms attributable to ARTs at three months post-intervention ( mean difference=0.33 ; 95 % confidence interval [CI]=0.01 , 0.66 ; t(132)=2.04 , P=0.044 ) and six months post-intervention ( mean difference=0.38 ; 95 % CI=0.05 , 0.71 ; t(132)=2.27 , P=0.025 ) . MBSR participants also experienced a reduction in distress associated with those symptoms at three months post-intervention ( mean difference=0.47 ; 95 % CI=0.003 , 0.94 ; t(132)=1.99 , P=0.048 ) compared with the WLC condition . CONCLUSION MBSR is a promising approach for reducing HIV treatment-related side effects AIM Reductions in substance use were examined in response to an intensive intervention with people living with human immunodeficiency virus ( HIV ) ( PLH ) . DESIGN , SETTING AND PARTICIPANTS A r and omized controlled trial was conducted with 936 PLH who had recently engaged in unprotected sexual risk acts recruited from four US cities : Milwaukee , San Francisco , New York and Los Angeles . Substance use was assessed as the number of days of use of 19 substances recently ( over the last 90 days ) , evaluated at 5-month intervals over 25 months . INTERVENTION A 15-session case management intervention was delivered to PLH in the intervention condition ; the control condition received usual care . MEASUREMENTS An intention-to-treat analysis was conducted examining reductions on multiple indices of recent substance use calculated as the number of days of use . FINDINGS Reductions in recent substance use were significantly greater for intervention PLH compared to control PLH : alcohol and /or marijuana use , any substance use , hard drug use and a weighted index adjusting for seriousness of the drug . While the intervention-related reductions in substance use were larger among women than men , men also reduced their use . Compared to controls , gay and heterosexual men in the intervention reduced significantly their use of alcohol and marijuana , any substance , stimulants and the drug severity-weighted frequency of use index . Gay men also reduced their hard drug use significantly in the intervention compared to the control condition . CONCLUSIONS A case management intervention model , delivered individually , is likely to result in significant and sustained reductions in substance use among PLH & NA ; This secondary analysis used E. Goffman 's ( 1963 ) model of stigma to examine how social support and health status are related to HIV stigma , after controlling for specific sociodemographic factors , and how these relationships differed between men and women living with HIV . Baseline data from 183 subjects in a behavioral r and omized clinical trial were analyzed using multigroup structural equation modeling . Women reported significantly higher levels of stigma than men after controlling for race , history of injection drug use , and exposure category . HIV‐related stigma was negatively predicted by social support regardless of gender . The theorized model explained a significant amount of the variance in stigma for men and women ( 24.4 % and 44 % , respectively ) and may provide novel and individualized intervention points for health care providers to effect positive change in perceived stigma for the person living with HIV . The study offers insight into underst and ing the relationships among gender , health status , social support , and HIV‐related stigma OBJECTIVE To determine the efficacy of a family intervention in reducing human immunodeficiency virus ( HIV ) risk behaviors among Hispanic delinquent adolescents . DESIGN R and omized controlled trial . SETTING Miami-Dade County Public School System and Miami-Dade County 's Department of Juvenile Services , Florida . PARTICIPANTS A total of 242 Hispanic delinquent youth aged 12 to 17 years and their primary caregivers completed outcome assessment s at baseline and 3 months after intervention . INTERVENTION Participants were r and omized to either Familias Unidas ( 120 participants ) , a Hispanic-specific , family intervention design ed to reduce HIV risk behaviors among Hispanic youth , or a community practice control condition ( 122 participants ) . MAIN OUTCOME MEASURES Self-reported measures included unprotected sexual behavior , engaging in sex while under the influence of alcohol and /or drugs , number of sexual partners , and incidence of sexually transmitted diseases . Family functioning ( eg , parent-adolescent communication , positive parenting , and parental monitoring ) was also assessed via self-report measures . RESULTS Compared with community practice , Familias Unidas was efficacious in increasing condom use during vaginal and anal sex during the past 90 days , reducing the number of days adolescents were under the influence of drugs or alcohol and had sex without a condom , reducing sexual partners , and preventing unprotected anal sex at the last sexual intercourse . Familias Unidas was also efficacious , relative to community practice , in increasing family functioning and most notably in increasing parent-adolescent communication and positive parenting . CONCLUSION These results suggest that culturally tailored , family-centered prevention interventions may be appropriate and efficacious in reducing HIV risk behaviors among Hispanic delinquent adolescents . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01257022 OBJECTIVE To evaluate the acceptability , practicality , and short-term efficacy of a health education program to improve disease self-management in patients with symptomatic HIV/AIDS . DESIGN R and omized controlled trial , baseline and 3-month follow-up question naire assessment s. SETTING San Francisco Bay communities . PARTICIPANTS Seventy-one men with symptomatic HIV or AIDS were r and omly assigned to a seven-session group educational intervention ( N=34 ) or a usual-care control group ( N=37 ) . INTERVENTION Interactive health education groups were used to teach wide-ranging disease self-management skills and information : symptom assessment and management , medication use , physical exercise , relaxation , doctor-patient communication , and nutrition . Each group was led by two trained peer-leaders ( one of whom was HIV-positive ) recruited from the community . MAIN OUTCOME MEASURES The primary outcome of interest was symptom status . Secondary outcomes were self-efficacy and health behaviors . Analysis of covariance was used to compare experimental and control group mean outcomes , adjusting for baseline value differences . RESULTS The symptom severity index ( number of symptoms moderate or greater severity ) decreased in the experimental , and increased in the control group ( -0.9 versus + 0.5 ; p < .03 ) . Pain , fatigue , and psychological symptoms were not significantly different between groups . Self-efficacy for controlling symptoms improved in the experimental , and decreased in the control group ( + 4 versus -7 ; p < .02 ) . Changes in stress/relaxation exercises and HIV/AIDS knowledge were not different between groups . A trend was shown toward more frequent physical exercise in the experimental group compared with less in the control group ( + 1.3 versus -0.5 times/week ; p=.06 ) . CONCLUSIONS Health education emphasizing self-management skills for HIV/AIDS patients can be implemented and evaluated and was accepted by patients , peer-leaders , and health care providers . Whether this educational program can lead to prolonged improvement in HIV symptoms and behaviors can be adequately addressed only by a larger trial of longer duration The authors sought to study the longitudinal effects of a cognitive-behavioral group intervention for coping with AIDS bereavement among a diverse sample of adults who were HIV positive . Participants ( N = 267 ) were r and omly assigned to receive the 12-week intervention or individual therapy upon request . Measures were administered at baseline , postintervention , and 4- , 8- , and 12-month follow-ups . Longitudinal data were analyzed with linear mixed models to examine change in grief by condition across the study period and the effect of the intervention on grief through its interaction with psychiatric distress . The authors used the Grief Reaction Index to assess grief and the Symptom Checklist-90-Revised to assess global psychiatric distress . Participants in both conditions reported decreases in grief severity . However , among those with higher levels of psychiatric distress , participants in the group intervention had significantly lower grief severity scores compared with participants in the individual therapy condition . The long-term effectiveness of this AIDS-bereavement intervention for psychiatrically distressed people with HIV/AIDS supports the need for tailored interventions among those at risk for complicated grief responses Questions remain regarding the clinical utility of psychological interventions for HIV-positive persons because r and omized controlled trials have utilized stringent inclusion criteria and focused extensively on gay men . The present r and omized controlled trial examined the efficacy of a 15-session , individually delivered cognitive-behavioral intervention ( n = 467 ) compared to a wait-list control ( n = 469 ) in a diverse sample of HIV-positive persons who reported HIV transmission risk behavior . Five intervention sessions that dealt with executing effective coping responses were delivered between baseline and the 5 months post-r and omization . Additional assessment s were completed through 25 months post-r and omization . Despite previously documented reductions in HIV transmission risk , no intervention-related changes in psychosocial adjustment were observed across the 25-month investigation period . In addition , there were no intervention effects on psychosocial adjustment among individuals who presented with mild to moderate depressive symptoms . More intensive mental health interventions may be necessary to improve psychosocial adjustment among HIV-positive individuals People living with HIV ( PLWH ) report elevated levels of posttraumatic stress disorder symptoms ( PTSS ) and associated comorbidities . The present study tested the efficacy of prolonged exposure ( PE ) at reducing PTSS , depression , negative posttraumatic cognitions , and substance use in PLWH . Participants were r and omly assigned to receive PE ( n = 40 ) or to a weekly monitoring control group ( n = 25 ) . Assessment s occurred at baseline , post-intervention and 3-months post-treatment . Following the 3-month assessment , controls were offered the intervention . All PE recipients ( whether originally from the PE or control group ) completed a 6-month assessment . Intent-to-treat mixed model repeated measures ANOVAs were conducted through 3-months post-treatment ; within group analyses were conducted through 6-months . PE recipients reported fewer PTSS and negative posttraumatic cognitions and were more likely to achieve good end-state functioning ; gains were maintained at 6-months . No between-group differences emerged for substance use . Overall , results support the efficacy of PE in PLWH.ResumenLas personas que viven con VIH ( PLWH por sus siglas en inglés ) presentan niveles elevados de los síntomas de trastorno de estrés postraumático ( TEPT ) y las comorbilidades asociadas . En el estudio actual se examinó la eficacia de la exposición prolongada ( EP ) por la reducción de TEPT , la depresión , las cogniciones postraumáticas negativas , y el uso de sustancias en PLWH . Los participantes fueron asignados de manera aleatoria a recibir la EP ( n = 40 ) , o a un grupo control con supervisión semanal ( n = 25 ) . Las evaluaciones fueron realizadas a la línea base , después de la intervención , y a los 3 meses después del tratamiento . Terminada esta última evaluación , se les ofreció la intervención a los miembros del grupo de control . Todos los receptores de la EP ( sean originalmente miembros del grupo EP o del control ) completaron una evaluación a los 6 meses . Se realizaron los ANOVAs de medidas repetidas y modelos mixtos por intención de tratamiento hasta los 3 meses después del tratamiento ; los análisis dentro del grupo se llevaron a cabo hasta los 6 meses . Los receptores de la EP mostraron menos síntomas de TEPT y cogniciones postraumáticas negativas , y tuvieron más probabilidad de lograr buen funcionamiento en el estado final ; los beneficios se mantenían a los 6 meses . No hubo diferencias entre los grupos en cuanto al uso de sustancias . En general , los result ados apoyan la eficacia de la EP en PLWH BACKGROUND Bereavement is a severe and frequent stressor among those infected with human immunodeficiency virus type 1 ( HIV-1 ) and those affected by the acquired immunodeficiency syndrome epidemic . This study examined the impact of a research -derived , semistructured , bereavement support group among HIV-1-seropositive and HIV-1-seronegative homosexual men having lost a close friend or intimate partner to the acquired immunodeficiency syndrome within the prior 6 months . METHODS A total of 166 subjects ( 97 HIV-1 seropositive ; 69 HIV- 1 seronegative ) were r and omly assigned to groups of homogeneous HIV-1 serostatus or to their respective control group . Subjects were assessed at entry and at 10 weeks with psychosocial question naires , a semistructured interview for psychopathology , a medical history and physical examination , urine collection , and phlebotomy . RESULTS For a composite score of psychological distress and grief as well as the distress component , scores were significantly lower after the intervention by analyses against baseline scores , with and without control variables for other factors affecting distress level . A significant reduction in grief level was found only in the analysis that included control variables . Control subjects showed no significant decrements in overall distress , although a significant decrement in grief level was observed . CONCLUSION A brief group intervention can significantly reduce overall distress and accelerate grief reduction in a sample of bereaved subjects unselected for psychopathology or at high risk for subsequent maladjustment OBJECTIVE Risk for developing cervical neoplastic disease is greatly increased in women infected with oncogenic sexually transmitted human papillomaviruses ( HPVs ) and who have lowered cellular immunity due to coinfection with human immunodeficiency virus ( HIV ) infection . The majority of these individuals are low-income minority women . Factors associated with promotion of HPV to cervical neoplasia in HIV-infected population s include degree of immunosuppression as well as behavioral factors such as tobacco smoking and psychological stress . This study examined the effects of a cognitive behavioral stress management ( CBSM ) intervention on life stress and cervical neoplasia in HIV+ minority women . METHODS Participants were 39 HIV+ African-American , Caribbean , and Hispanic women with a recent history of an abnormal Papanicolaou smear . Participants underwent colposcopic examination , psychosocial interview , and peripheral venous blood draw at study entry and 9 months after being r and omly assigned to either a 10-week CBSM group intervention ( n=21 ) or a 1-day CBSM workshop ( n=18 ) . RESULTS Women assigned to the 10-week group-based CBSM intervention reported decreased perceived life stress and had significantly lower odds of cervical neoplasia over a 9-month follow-up . CBSM effects on life stress and neoplasia appeared independent of presence of neoplasia at study entry , HPV type , CD4+CD3 + cell count , HIV viral load , and substance use . Furthermore , CBSM intervention effects on cervical neoplasia were especially pronounced among women with residual life stress at follow-up . CONCLUSION These findings suggest that stress management decreases perceived life stress and may decrease the odds of cervical neoplasia in women with HIV and a history of abnormal Papanicolaou smears . Although preliminary , these findings suggest the utility of stress management as a cancer prevention strategy in this high-risk population Abstract The prevalence of HIV infection continues to increase among women in South Africa while there are few interventions specifically targeting condom use promotion in this population . We report the results of an experimental pilot study of a health education intervention aim ed at enhancing coping skills and consistent condom use among HIV-positive women attending primary health clinics in the Western Cape province of South Africa . One hundred and twenty women were r and omised into the intervention condition or a control condition . Both groups completed an interviewer administered question naire that included measures of self-esteem , attitude towards condom use , and self-efficacy towards condom use and negotiating condom use , and provided vaginal swab specimen at baseline and three months after the intervention . Tests for intervention effects at three months while controlling for baseline revealed that only self-esteem was significantly higher in the intervention group relative to the control group . No significant differences were found on measures of coping skills and condom use behaviour . Importantly , incidence for Chlamydia Trachomatis , Neisseria Gonorrhea and Trichomona vaginalis during the study period were significantly lower in the intervention group than the control group . These results are strong indications that this intervention could serve as a basis for the development of potentially effective interventions to reduce STI-related sexual risk behaviours among HIV-positive black women in South Africa BACKGROUND This r and omized clinical trial compared 16-week interventions with interpersonal psychotherapy , cognitive behavioral therapy , supportive psychotherapy , and supportive psychotherapy with imipramine for human immunodeficiency virus (HIV)-positive patients with depressive symptoms . METHODS Subjects ( N = 101 ; 85 male , 16 female ) with known HIV seropositivity for at least 6 months were r and omized to 16 weeks of treatment . Inclusion criteria were 24-item Hamilton Depression Rating Scale score of 15 or higher , clinical judgment of depression , and physical health sufficient to attend outpatient sessions . Therapists were trained in manualized therapies specific for HIV-positive patients . Treatment adherence was monitored . RESULTS Subjects r and omized to interpersonal psychotherapy ( n = 24 ) and supportive psychotherapy with imipramine ( n = 26 ) had significantly greater improvement on depressive measures than those receiving supportive psychotherapy ( n = 24 ) or cognitive behavioral therapy ( n = 27 ) . Similar results appeared in the completer sub sample . CONCLUSIONS Depressive symptoms appear treatable in HIV-positive patients . Interpersonal psychotherapy may have particular advantages as a psychotherapy for patients who have experienced the significant life events of HIV infection OBJECTIVE To evaluate cognitive-behavioral therapy to enhance medication adherence and reduce depression ( CBT-AD ) in individuals with HIV . DESIGN A two arm , r and omized , controlled , cross-over trial comparing CBT-AD to enhanced treatment as usual only ( ETAU ) . ETAU , which both groups received , included a single-session intervention for adherence and a letter to the patient 's provider documenting her or his continued depression . The intervention group also received 10 to 12 sessions of CBT-AD . MAIN OUTCOME MEASURES Adherence to antiretroviral therapy as assessed by Medication Event Monitoring Systems ( MEMs ) and depression as assessed by blinded structured evaluation . RESULTS At the acute outcome assessment ( 3-months ) , those who received CBT-AD evidence d significantly greater improvements in medication adherence and depression relative to the comparison group . Those who were originally assigned to the comparison group who chose to cross over to CBT-AD showed similar improvements in both depression and adherence outcomes . Treatment gains for those in the intervention group were generally maintained at 6- and 12-month follow-up assessment s. By the end of the follow-up period , those originally assigned CBT-AD demonstrated improvements in plasma HIV RNA concentrations , though these differences did not emerge before the cross-over , and hence there were not between-groups differences . CONCLUSIONS CBT-AD is a potentially efficacious approach for individuals with HIV struggling with depression and adherence . Replication and extension in larger efficacy trials are needed The purpose of this study was to examine the impact of a group coping intervention for HIV-positive men and women who have lost a loved one(s ) to AIDS in the past 2 years . Two hundred thirty-five participants , diverse with respect to race/ethnicity and sexual orientation , were r and omly assigned to a 12-week cognitive-behavioral group intervention or to an individual therapy on request comparison condition . Measures assessing grief and psychiatric distress were administered at baseline and 2 weeks post-intervention period . Although a strong gender effect was observed in outcome , both men and women participating in the group intervention demonstrated significantly more reduction in psychiatric distress than controls . Further , women in the group intervention demonstrated significant reductions in grief and depressive symptoms over men in both conditions and women in the comparison condition . Brief cognitive-behavioral group interventions for coping with grief have a positive impact on the psychiatric functioning of HIV-positive participants . This appears to be especially true for HIV-positive women ; a group not previously focused on in clinical research related to AIDS bereavement Abstract The aim of this exploratory study was to examine the possible mechanisms of behavioral change in a cognitive – behavioral intervention supporting medication adherence in HIV-infected persons . A total of 60 persons currently under medical treatment were r and omized to psychotherapy or usual care and were compared with a sociodemographically matched group of general psychotherapy clients . Outcome measures included therapy adherence using medication event-monitoring system psychotherapeutic processes and changes of experience and behavior . The general psychotherapy group was initially more distressed than HIV psychotherapy patients and reached higher levels of psychotherapeutic effect . In the HIV psychotherapy patients , a significant effect was found for maintaining adherence to medical treatment ( Weber et al. , 2004 ) . These findings show that psychotherapy is a beneficial intervention for HIV-infected persons , and therapeutic alliance and activation of re sources do not differ from a general psychotherapy treatment . Differential effects were detected for specific process variables , namely problem actuation BACKGROUND Co-morbid depression in HIV-positive patients on anti-retroviral ( ART ) treatment poses a public health threat . It compromises treatment adherence and accelerates disease progression . This study aim ed to assess the feasibility of a group-based counselling intervention for depressed HIV-positive patients in primary health care ( PHC ) in South Africa using a task shifting approach . METHODS Using a r and omized control design , 76 HIV-positive patients with co-morbid depression were initially recruited . This reduced to 34 in the final cohort . Participants were assessed using the Patient Health Question naire ( PHQ9 ) , Hopkins Symptom Checklist ( HSCL-25 ) and Multidimensional Scale of Perceived Social Support ( MSPSS ) at baseline and 3-month follow-up . The intervention was adapted from a local group-based Interpersonal Therapy ( IPT ) intervention . Process evaluation interviews were held with the HIV counsellors who delivered the intervention and a sub- sample of participants . RESULTS Repeated measures ANOVA analysis showed significantly greater improvement on depression scores on the PHQ9 in the intervention group compared to the control group . A significant decline in the mean scores on the HSCL-25 was found for both groups although this was more pronounced for the intervention group . There was no significant improvement in the MSPSS scores . LIMITATIONS The small sample size of the final cohort affected the power of the study to detect significant differences between the intervention and control groups on the MSPSS . Longer term impact of the intervention is unknown . CONCLUSIONS These preliminary findings suggest that group-based counselling for depression in HIV-positive patients can potentially be effectively delivered by appropriately trained and supported lay HIV counsellors . The need for a larger trial is indicated OBJECTIVE To evaluate Positive Choices ( PC ) , a program that employed lay health workers to motivate antiretroviral adherence among persons living with HIV with coverage from Indiana 's high-risk insurance pool . METHODS Four hundred and forty nine participants living in the greater Indianapolis area were r and omly allocated to treatment ( n = 91 ) or control ( n = 358 ) groups and followed for one year . RESULTS Compared to control subjects , PC subjects were more likely to adhere to HIV medications ( medication possession ratio adherence ≥ 0.95 , OR = 1.83 , p = 0.046 ) , and to achieve undetectable viral load ( < 50 copies/mL , OR = 2.01 , p = 0.011 ) in the 12 months following introduction of PC . There were no significant differences observed between groups in any of self-reported health status indicators . CONCLUSION Estimates suggest that PC clients were 16 % more likely to have undetectable viral loads than clients in st and ard care . The incremental program cost was approximately $ 10,000 for each additional person who achieved an undetectable viral load . PRACTICE IMPLICATION S As persons living with HIV experience greater longevity and healthcare reform exp and s coverage to these high-risk population s , greater dem and s will be placed on the HIV-care workforce . Results suggest lay health workers may serve as effective adjuncts to professional care providers Abstract The present study evaluated the efficacy of an individualized psycho-education ( PE ) program in reducing psychological distress and risky sexual behavior and enhancing self-disclosure associated with an HIV diagnosis among attendees of a walk-in non-governmental voluntary counseling and testing ( VCT ) center in Nigeria . Ninety-four consecutive individuals were asked to complete a pre-counseling , baseline question naire detailing their sociodemographic characteristics , psychopathology , sexual practice s , self-disclosure intention and coping behaviors . They were screened for HIV and post-test counseled . Sixty-seven individuals ( 72.2 % ) who tested positive were consecutively r and omly assigned to one of two groups : a PE program ( four 60-minute weekly manual driven sessions ) ( N=34 ) and a wait-list ( WL ) control group ( N=33 ) . The major outcome measures used were the Crown Crisp Experiential Index ( CCEI ) , the Beck Depression Inventory ( BDI ) ( Beck et al. , ( 1961 ) , self-report sexual practice s in past three months , self-disclosure intention and the brief COPE . At four weeks post-intervention , significant reductions on all measures as well as reduction in risky sexual practice s were observed in the treatment group compared with the wait-list group . Treatment group members were also significantly more likely to disclose their serostatus and accept their HIV status as a way of coping , compared with the wait-list group . Overall , support was found for the efficacy of a manual-driven PE program for self-disclosure , reduction of depression and improvement in safe sexual practice The effects of a 10-week group-based cognitive-behavioral stress management ( CBSM ) intervention on psychological distress and plasma free testosterone in symptomatic , HIV-seropositive men were examined . Participants were r and omized to either CBSM ( n = 42 ) or a wait-list control group ( n = 23 ) . Men in the CBSM intervention showed significant increases in testosterone , whereas control participants showed significant decreases . Those participating in CBSM had significant distress reductions , whereas controls showed no such change . Alterations in free testosterone were inversely related to changes in distress states over time , independent of any changes in cortisol . These findings demonstrate that a short-term CBSM intervention increases free testosterone levels among symptomatic , HIV-seropositive men , and alterations in free testosterone are associated with changes in psychological distress observed during CBSM This study tests the efficacy of Structural Ecosystems Therapy ( SET ) , a family-ecological intervention , in improving psychosocial functioning when compared with an attention-comparison person-centered condition and a community control condition . A sample of 209 HIV-seropositive , urban , low-income , African American women was r and omized into 1 of the 3 conditions . Results of growth curve analyses over 5 time points revealed that SET was more efficacious than either of the control conditions in reducing psychological distress and family-related hassles . However , contrary to hypotheses , SET was not more efficacious in increasing family support . Latent growth mixture modeling analyses indicated that SET was most efficacious for women who , on average , were at or near the clinical threshold for psychological distress and for women with high levels of family hassles . Implication s for further intervention development are discussed Results of a r and omized controlled trial show that a behavioral intervention grounded in social cognitive theory reduces unprotected sexual behaviors among men and women living with HIV infection , with the greatest reductions in HIV transmission risk behaviors occurring with non-HIV-positive sex partners . In this article , the authors describe the intervention development and intervention content of the social cognitive risk reduction intervention for HIV-positive persons . The effective five group session intervention focused on enhancing motivation through self-reflection and developing coping efficacy skills for HIV disclosure decision making , active listening , assertiveness , and problem solving for disclosure and transmission risk reduction behaviors . Intervention components were tailored for gender and sexual orientation and integrated skills practice sessions used role-plays couched within scenes from popular films . This intervention was demonstrated to be effective in a community-service delivery setting and can be adapted for implementation in HIV-related services delivered within support groups The success of highly active antiretroviral therapy ( HAART ) among persons living with HIV is largely dependent on strict medication adherence . Recent research suggests that alcohol and other drug use ( AOD ) may be an important barrier to HAART adherence . In this study , we examined the impact of AOD on HAART adherence as well as the moderating effects of general and medication-specific social support . The data were collected as part of a longitudinal r and omized control trial with 224 HIV-positive patients at an HIV primary care clinic in the northwestern United States . Findings indicated that AOD use was negatively associated with HAART adherence and that medication-specific ( but not general ) social support moderated the AOD-adherence association at 3 ( but not at 6 or 9 ) months . Results indicate the importance of medication-specific social support to treat comorbid AOD use and HIV ; implication s for future research and intervention programs for HIV-positive AOD users are discussed Objective : To determine the effects of cognitive – behavioral stress management ( CBSM ) training on clinical and psychosocial markers in HIV-infected persons . Methods : A r and omized controlled trial in four HIV outpatient clinics of 104 HIV-infected persons taking combination antiretroviral therapy ( cART ) , measuring HIV-1 surrogate markers , adherence to therapy and well-being 12 months after 12 group sessions of 2 h CBSM training . Results : Intent-to-treat analyses showed no effects on HIV-1 surrogate markers in the CBSM group compared with the control group : HIV-1 RNA < 50 copies/ml in 81.1 % [ 95 % confidence interval ( CI ) , 68.0–90.6 ] and 74.5 % ( 95 % CI , 60.4–85.7 ) , respectively ( P = 0.34 ) , and mean CD4 cell change from baseline of 53.0 cells/μl ( 95 % CI , 4.1–101.8 ) and 15.5 cells/μl ( 95 % CI , −34.3 to 65.4 ) , respectively ( P = 0.29 ) . Self-reported adherence to therapy did not differ between groups at baseline ( P = 0.53 ) or at 12 month 's post-intervention ( P = 0.47 ) . Significant benefits of CBSM over no intervention were observed in mean change of quality of life scores : physical health 2.9 ( 95 % CI , 0.7–5.1 ) and −0.2 ( 95 % CI , −2.1 to 1.8 ) , respectively ( P = 0.05 ) ; mental health 4.8 ( 95 % CI , 1.8–7.3 ) and −0.5 ( 95 % CI , −3.3 to 2.2 ) ( P = 0.02 ) ; anxiety −2.1 ( 95 % CI , −3.6 to −1.0 ) and 0.3 ( 95 % CI , −0.7 to 1.4 ) , respectively ( P = 0.002 ) ; and depression −2.1 ( 95 % CI , −3.2 to −0.9 ) and 0.02 ( 95 % CI , −1.0 to 1.1 ) , respectively ( P = 0.001 ) . Alleviation of depression and anxiety symptoms were most pronounced among participants with high psychological distress at baseline . Conclusion : CBSM training of HIV-infected persons taking on cART does not improve clinical outcome but has lasting effects on quality of life and psychological well-being Forty-six Chinese patients with symptomatic human immunodeficiency virus ( HIV ) participated in a comparative study assessing the effectiveness of cognitive-behavioral group therapy ( CBT ) and peer support/counseling group therapy ( PSC ) in relation to improving mood and quality of life and decreasing uncertainty in illness as compared to a group receiving routine treatment with no formal psychosocial intervention . The CBT group consisted of 10 subjects , the PSC group of 10 subjects , and the comparison group of 26 subjects . There was a 24 % attrition rate . The intervention groups received 12 weekly sessions of therapy over 3 months . Assessment of mood states was carried out before r and omization ( baseline data ) , immediately postintervention ( 3-month time point ) and followed-up 3 months later ( 6-month time point ) . Assessment of quality of life and uncertainty in illness was carried out before r and omization and at the 6-month follow-up time point . Results indicated that the mood of the participants in the CBT group improved in terms of anger , tension-anxiety , depression , confusion , and overall mood . The quality of life in this group was significantly improved compared to the other two groups , as was uncertainty in illness . In the PSC group a worsening of psychologic functioning was observed immediately postintervention , but this picture dramatically improved at the follow-up assessment with improvements of up to 34 % . Quality of life also improved over time in this group by almost 5 % , but results did not reach statistical significance . This study demonstrated that psychologic interventions could decrease psychologic distress and improve quality of life in symptomatic HIV patients , indicating their use should be incorporated in the management of care of people living with HIV/AIDS Objective : We conducted a r and omized , multi-site , controlled trial of a cognitive-behavioral adherence intervention for patients initiating or changing an antiretroviral ( ART ) regimen . Design : A 3 × 2 factorial design was used with the primary r and omization assigning patients ( 1 : 1 : 1 ) to one of two adherence interventions or usual care . Methods : The five-session adherence interventions consisted of cognitive – behavioral and motivational components , with or without a 2-week pre-treatment placebo practice trial . Intent-to-treat analysis used probability weights and regression tree analysis to account for missing data . Results : A total of 230 patients were r and omized ; 199 started ART , of whom 74 % completed the 48-week study . Electronic monitored adherence outcomes between the two intervention groups did not differ significantly and were thus pooled in analyses . At week 4 , 82 % of intervention patients had taken at least 90 % of their prescribed ART doses , compared with 65 % of controls ( P < 0.01 ) ; this group difference dropped to 12 % at week 12 ( 72 versus 60 % ; P = 0.15 ) and 11 % at week 24 ( 66 versus 55 % ; P = 0.28 ) . Mean adherence in the intervention group was significantly higher than the control group at week 24 ( 89 versus 81 % ; P < 0.05 ) only . There were no group differences with respect to HIV-1 RNA throughout the study . Conclusions : The effects of the cognitive – behavioral intervention on adherence were modest and transient , and no effects were observed on viral load or CD4 cell count . More robust effects may require a more intense intervention that combines ongoing adherence monitoring and individualized intervention ‘ dosage ’ that matches the need and performance of each patient Objective To evaluate the efficacy of an intervention to reduce HIV transmission risk behaviors and sexually transmitted diseases ( STDs ) and enhance HIV-preventive psychosocial and structural factors among women living with HIV . Design A r and omized controlled trial of 366 women living with HIV in Alabama and Georgia . InterventionThe intervention emphasized gender pride , maintaining current and identifying new network members , HIV transmission knowledge , communication and condom use skills , and healthy relationships . Primary Outcome Unprotected vaginal intercourse . Other Outcomes Proportion never used condoms , incident STDs , psychosocial factors , and number of supportive network members . Results Over the 12-month follow-up , women in the WiLLOW intervention , relative to the comparison , reported fewer episodes of unprotected vaginal intercourse ( 1.8 vs. 2.5 ; P = 0.022 ) ; were less likely to report never using condoms ( odds ratio [ OR ] = 0.27 ; P = 0.008 ) ; had a lower incidence of bacterial infections ( Chlamydia and gonorrhea ) ( OR = 0.19 ; P = 0.006 ) ; reported greater HIV knowledge and condom use self-efficacy , more network members , fewer beliefs that condoms interfere with sex , and fewer partner-related barriers to condom use ; and demonstrated greater skill in using condoms . Conclusion This is the first trial to demonstrate reductions in risky sexual behavior and incident bacterial STDs and to enhance HIV-preventive psychosocial and structural factors among women living with HIV We assessed the effectiveness of the treatment supporter initiative as an intervention in improving clinic attendance for antiretroviral ( ARV ) drug refills and adherence to antiretroviral therapy ( ART ) in a cohort of HIV-infected adults . This two-arm r and omized controlled trial was undertaken at an HIV clinic in a district hospital in Ug and a. A total of 174 adult patients on ART were r and omized 1:1 to a st and ard adherence intervention package plus a treatment supporter intervention ( TS arm ) or to a st and ard adherence intervention package ( non-TS arm ) alone . Clinic attendance for refills and adherence measurements using monthly clinic-based pill counts were monitored for both arms for 28 weeks . Baseline characteristics were similar for both arms . There was a non-significant difference in mean adherence between the TS and non-TS groups at end of follow-up [ 99.1 % ( 95 % CI : 98.3–99.9 % vs. 96.3 % ( 95 % CI : 94.2–98.3 % ) , P > 0.05 ] . TS participants had more than four times the odds of achieving optimal adherence ( ≥95 % ) [ Odds ratio ( OR ) = 4.51 , 95 % CI : 1.22–16.62 , exact P = 0.027 ] . TS participants were also more likely to be on time for their clinic appointments : 91.6 vs. 90.1 % for TS and non-TS , respectively ( OR = 1.19 , 95 % CI : 0.74–1.91 , P > 0.05 ) . Use of patient-selected treatment supporters may be an effective intervention to improve ARV treatment outcomes in re source -constrained setting We evaluate the efficacy of a family-based intervention over time among HIV-affected families . Mothers living with HIV ( MLH ; n = 339 ) in Los Angeles and their school-aged children were r and omized to either an intervention or control condition and followed for 18 months . MLH and their children in the intervention received 16 cognitive-behavioral , small-group sessions design ed to help them maintain physical and mental health , parent while ill , address HIV-related stressors , and reduce HIV-transmission behaviors . At recruitment , MLH reported few problem behaviors related to physical health , mental health , or sexual or drug transmission acts . Compared to MLH in the control condition , intervention MLH were significantly more likely to monitor their own CD4 cell counts and their children were more likely to decrease alcohol and drug use . Most MLH and their children had relatively healthy family relationships . Family-based HIV interventions should be limited to MLH who are experiencing substantial problems BACKGROUND Group support psychotherapy ( GSP ) is a culturally sensitive intervention that aims to treat depression by enhancing social support , teaching coping skills , and income-generating skills . We compared GSP with group HIV education ( GHE ) for treatment of depression in people with HIV in Ug and a. METHODS In this open-label r and omised controlled trial , we included men and women with HIV , aged 19 years or older , who met the Mini International Neuropsychiatric Interview criteria for major depression from an urban HIV care centre in Kitgum district , northern Ug and a. Participants were r and omly assigned to receive eight weekly sessions of either GSP or GHE . R and omisation was achieved by urn ( men and women separately picked a paper containing the intervention allocation from a basket ; ratio 1:1 ) , and the intervention sessions were given to gender-specific groups . Participants were followed up immediately after the intervention and 6 months after the end of treatment . The primary outcomes were change in depressive symptom scores ( measured with the Self-Reporting Question naire ) and in function scores ( measured with a locally developed method ) , analysed by intention to treat using cluster-adjusted t tests and permutation tests . This trial is registered with The Pan African Clinical Trials Registry , number PACTR201402000742370 . FINDINGS Between Jan 6 , and Jan 20 , 2014 , we assessed 150 individuals , of whom 109 were r and omly assigned to receive eight weekly sessions of either GSP ( n=57 ) or GHE ( n=52 ) . Change in mean depression scores immediately after intervention did not differ between groups ( mean difference -0·19 , 95 % CI -1·77 to 1·39 , p=0·78 ) . Mean function scores did not differ between groups either ( 0·24 , -0·41 to 0·88 ; p=0·41 ) . At 6 months after end of treatment , participants in the GSP group had lower mean depression scores than did those in the GHE group ( -2·50 , -3·98 to 1·02 , p value=0·005 ) , and higher function scores ( 0·74 , -0·17 to 1·65 , p=0·09 ) than did participants in the GHE group . No adverse events were reported . INTERPRETATION The benefits of existing HIV educational interventions in HIV care services could be improved by the addition of GSP content . Potential benefits of the integration of GSP into existing HIV interventions , such as adherence counselling or group HIV educational programmes , should be addressed in future studies . FUNDING Gr and Challenges Canada Abstract The purpose of this study was to evaluate a novel psycho-educational intervention intended to increase patients ’ medication preparedness and treatment adherence skills before initiating highly active antiretroviral therapy ( HAART ) . Sixty-three HIV-positive patients not currently on antiretroviral therapy participated in a r and omized controlled trial of a st and ardized , four-session psycho-educational intervention ( Supportive Therapy for Adherence to Antiretroviral Treatment ; STAART ) . Session topics included learning techniques to increase medication adherence and learning effective strategies to cope with stress and depression . Patients completed psychological question naires assessing psychological readiness to initiate HAART and depressed mood . They completed both measures at study baseline and at four-weeks post-baseline . After controlling for baseline medication readiness scores , intervention patients ( n=30 ) reported significantly higher mean medication readiness following the STAART intervention ( four-weeks post-baseline ) ( 27.3±6.9 ) compared to controls ( n=33 ; 24.6±9.9 ; p<0.05 ) . Among depressed patients ( n=27 ) , those receiving the intervention ( n=15 ) reported significantly lower mean depression scores at four-weeks post-baseline ( 22.5±12.9 ) compared to controls ( n=12 ; 27±9.9 ; p<0.05 ) . The STAART intervention enhanced HIV treatment readiness by better preparing patients prior to initiating HAART . It was also beneficial for reducing depressive symptoms in depressed , HIV-positive patients OBJECTIVE Depression and substance use , the most common comorbidities with HIV , are both associated with poor treatment adherence . Injection drug users comprise a substantial portion of individuals with HIV in the United States and globally . The present study tested cognitive behavioral therapy for adherence and depression ( CBT-AD ) in patients with HIV and depression in active substance abuse treatment for injection drug use . METHOD This is a 2-arm , r and omized controlled trial ( N = 89 ) comparing CBT-AD with enhanced treatment as usual ( ETAU ) . Analyses were conducted for two time-frames : ( a ) baseline to post-treatment and ( b ) post-treatment to follow-up at 3 and 6 months after intervention discontinuation . RESULTS At post-treatment , the CBT-AD condition showed significantly greater improvement than ETAU in MEMS ( electronic pill cap ) based adherence , γslope = 0.8873 , t(86 ) = 2.38 , p = .02 ; dGMA-raw = 0.64 , and depression , assessed by blinded assessor : Mongomery-Asberg Depression Rating Scale , F(1 , 79 ) = 6.52 , p < .01 , d = 0.55 ; clinical global impression , F(1 , 79 ) = 14.77 , p < .001 , d = 0.85 . After treatment discontinuation , depression gains were maintained , but adherence gains were not . Viral load did not differ across condition ; however , the CBT-AD condition had significant improvements in CD4 cell counts over time compared with ETAU , γslope = 2.09 , t(76 ) = 2.20 , p = .03 , dGMA-raw = 0.60 . CONCLUSIONS In patients managing multiple challenges including HIV , depression , substance dependence , and adherence , CBT-AD is a useful way to integrate treatment of depression with an adherence intervention . Continued adherence counseling is likely needed , however , to maintain or augment adherence gains in this population The feasibility and acceptability of cognitive behavior therapy for HIV-related peripheral neuropathic pain was examined and the potential efficacy of the intervention was compared with that of supportive psychotherapy in reducing pain , pain-related interference with functioning , and distress . Sixty-one patients were r and omly assigned to receive six weekly sessions of cognitive behavior therapy or supportive psychotherapy . Thirty-three subjects completed the protocol . Both groups showed significant reductions in pain . The cognitive behavior group improved in most domains of pain-related functional interference and distress ; the supportive psychotherapy group showed fewer gains . The high dropout rate suggests that psychotherapeutic treatments for HIV-related pain may have limited feasibility and acceptability Rationale and Purpose : Motivational interviewing ( MI ) is a counseling technique that has been used effectively to change a number of health-related behaviors . We sought to assess the impact on patients ' antiretroviral therapy ( ART ) adherence of a multicomponent , MI-based ART adherence intervention compared with that of an HIV informational control program . Study Design : Two-arm , r and omized , controlled trial . Sample : One hundred forty adult HIV-infected patients attending a large , academic center infectious diseases clinic who were either failing or newly initiating an ART regimen . Study Endpoints : ( 1 ) Mean adherence level ( % of prescribed doses take in the prior month ) at the week 12 visit , ( 2 ) change in mean adherence , ( 3 ) percentage of patients achieving > 95 % adherence in the third 4-week block , and ( 4 ) change in viral load . Main Findings : The MI group 's mean adherence improved by 4.5 % compared with a decrease in the control group 's adherence by 3.83 % ( P = 0.10 ) . In the treatment group , 29 % achieved > 95 % adherence compared with only 17 % in the control group ( P = 0.13 ) . When we controlled for ethnicity , the intervention group had 2.75 times higher odds of achieving more than 95 % adherence than did the controls ( P = 0.045 ; 95 % confidence interval : 1.023 , 7.398 ) . Although a number of mediating variables ( beliefs about ART , coping style , social support , and goals set ) had statistically significant changes in the expected direction in the MI group compared with controls , in the intent-to-treat analysis , the mean adherence at study exit for the intervention group was 76 % ( SD = 27 % ) and 71 % ( SD = 27 % ) for the control group ( P = 0.62 ) . Conclusion : Although not definitive , this study provides some evidence that MI offers an effective approach to improving adherence . Future studies able to build MI into the intervention for longer than 3 months may have a greater impact A network-oriented HIV prevention intervention based on social identity theory and peer outreach was implemented for HIV positive and negative drug users . A community sample of 250 were r and omly assigned to an equal-attention control condition or a multisession , small-group experimental condition , which encouraged peer outreach ; 94 % of participants were African American , and 66 % used cocaine or opiates . At follow-up , 92 % of participants returned , and experimental compared with control group participants were 3 times more likely to report reduction of injection risk behaviors and 4 times more likely to report increased condom use with casual sex partners . Results suggest that psychosocial intervention emphasizing prosocial roles and social identity , and incorporating peer outreach strategies , can reduce HIV risk in low-income , drug-using communities We conducted a preliminary RCT among 40 HIV-positive Latinos of Mexican descent on the U.S.-Mexico border who indicated imperfect adherence and depressive symptomatology . Participants were r and omly assigned to culturally adapted cognitive-behavioral therapy for adherence and depression with an alarmed pillbox or usual care . Outcomes were depressive symptoms ( self-report and blind clinician ratings ) , adherence ( self-report and electronic pillbox ) , and biological markers . The intervention , delivered in English and Spanish , proved feasible and acceptable . Generalized estimating equations in intent-to-treat analyses showed some effects of “ moderate ” to “ large ” size , with maintenance over time . For example , intervention ( vs. control ) participants demonstrated at post-intervention a greater drop in BDI scores ( OR = −3.64 , p = 0.05 ) and greater adherence according to the electronic pillbox ( OR = 3.78 , p = 0.03 ) . Biological markers indicated some relative improvement for CD4 count but not VL . The promising results suggest a larger trial to determine efficacy is warranted . ResumenLlevamos a cabo un estudio preliminar , aleatorizado y controlado ( RCT por sus siglas en inglés ) en la región fronteriza de Estados Unidos y México con 40 Latinos , VIH seropositivos , de descendencia Mexicana quienes reportaron adherencia imperfecta y sintomatología depresiva . Participantes fueron asignados aleatoriamente a una terapia cognitiva conductual ( la cual fue culturalmente adaptada ) para adherencia y depresión ( CBT-AD por sus siglas en inglés ) con uso de una caja de medicamentos equipada con alarma o a recibir el tratamiento estándar . Los variables de result ados fueron síntomas depresivos ( autoinforme y evaluación clínica hecho a ciegas ) , adherencia ( autoinforme y caja electrónica ) , y marcadores biológicos . La intervención , proveída en inglés y en español , demostró ser factible y aceptable . Análisis de las ecuaciones de estimación generalizada ( GEE ) y de intención de proveer el tratamiento demostraron efectos de tamaño “ moderado ” a “ gr and e ” , y también indicaron algo de mantenimiento tras el tiempo . Por ejemplo , en la etapa después que se terminó el tratamiento , los participantes en el grupo CBT-AD demostraron una reducción mas gr and e en puntuación de síntomas depresivos [ ( BDI ) OR = 3.64 , p = 0.05 ] y un mejoramiento en adherencia según los datos de la caja electrónica . Los marcadores biológicos mostraron algún mejoramiento en el nivel de las células CD4 pero no en la carga viral . Estos result ados son positivos y sugieren que un estudio más extenso sería justificado OBJECTIVE The feasibility and effectiveness of a combination of group cognitive-behavioral therapy and medication for the treatment of depression among gay men with AIDS or symptomatic HIV infection were evaluated . METHODS Fifteen patients diagnosed with DSM-IV major depressive disorder or dysthymia were treated in one of two weekly therapy groups in which cognitive-behavioral therapy had been specially modified for the target population . The majority of these patients , including two who had been on medication before joining the groups , also received antidepressant medication . Thirteen of the 15 patients completed therapy , attending an average of 15 of the 20 therapy sessions . RESULTS The group cognitive-behavioral therapy used in this project appeared to be attractive to most patients ; retention , attendance , and therapy compliance were good . Depression scores showed substantial decreases from pre- to posttherapy , with further decreases at one-year follow-up . Patients ' self-reports indicated that some aspects of the intervention , particularly the focus on cognitive restructuring , were especially valuable in alleviating their depression . CONCLUSIONS The modified group cognitive-behavioral therapy described in this study report offers a reasonable option for treatment of this clinical ly challenging group of patients BACKGROUND Psychotherapy is the recommended first line treatment for mild to moderate depression . However , its availability in low re source setting s is limited . We developed a manualized culturally sensitive group support psychotherapeutic intervention for depressed HIV affected Ug and an adults . In this study , we aim ed to assess its feasibility , acceptability and impact on depression , functioning , social support and self-esteem . METHODS A total of 77 depressed individuals were assigned to the group intervention ( n=48 ) and a wait-list control group ( n=29 ) , and assessed before , during and at the end of the intervention . The self-reporting question naire , a locally relevant function assessment instrument , the Rosenberg self-esteem scale , and the multiple dimensions perceived social support scale were administered to assess depression symptoms , functioning , self-esteem and social support at three assessment periods . Multivariate longitudinal regression models were used to determine change in outcomes over time between the two groups . Participants were asked to evaluate the intervention . RESULTS Post -intervention assessment s indicate that , in comparison to the wait-list control group , the intervention group had a faster reduction in depression symptom scores [ OR=0.00,95 % CI , 0.00 - 0.003 ] and faster increase in functioning scores [ OR=4.82 , 95 % CI , 2.39 to 9.75 ] , social support scores [ OR=2.68 , 95 % CI , 1.50 - 4.78 ] and self-esteem [ OR=1.90 , 95 % CI 1.48 - 2.44 ] . Sixty-three percent of participants strongly agreed that the intervention had reduced their depression and would recommend it to other depressed individuals . LIMITATIONS Inadequate study power due to small sample sizes may result in imprecise confidence intervals even when there are significant differences . The use of non-r and om sample s could have result ed in selection bias . CONCLUSIONS This intervention appears feasible , acceptable and promising in treating depression and restoring function , enhancing social support and self-esteem . Larger and r and omized evaluations are warranted BACKGROUND Crack cocaine use undermines adherence to highly active antiretroviral therapy ( HAART ) . This pilot r and omized clinical trial tested the feasibility and efficacy of 2 interventions based on the Information-Motivation-Behavioral Skill model to improve HAART adherence and reduce crack cocaine problems . METHODS Participants were 54 adults with crack cocaine use and HIV with < 90 % HAART adherence . Most participants were African-American ( 82 % ) heterosexual ( 59 % ) , and crack cocaine dependent ( 92 % ) . Average adherence was 58 % in the past 2 weeks . Average viral loads ( VL ) were detectable ( logVL 2.97 ) . The interventions included 6 sessions of Motivational Interviewing plus feedback and skills building ( MI+ ) , or Video information plus debriefing ( Video+ ) over 8 weeks . Primary outcomes were adherence by 14-day timeline follow-back and Addiction Severity Index ( ASI ) Drug Composite Scores at 3 and 6 months . Repeated measure ANOVA assessed main effects of the interventions and interactions by condition . RESULTS Significant increases in adherence and reductions in ASI Drug Composite Scores occurred in both conditions by 3 months and were maintained at 6 months , representing medium effect sizes . No between group differences were observed . No VL changes were observed in either group . Treatment credibility , retention , and satisfaction were high and not different by condition . CONCLUSIONS A counseling and a video intervention both improved adherence and drug problems durably among people with crack cocaine use and poor adherence in this pilot study . The interventions should be tested further among drug users with poor adherence . Video interventions may be feasible and scalable for people with HIV and drug use BACKGROUND The purpose of this r and omized double-blind , placebo-controlled study was to compare the efficacy and safety of fluoxetine plus group psychotherapy versus group psychotherapy alone in HIV-seropositive men ( based on 1986 CDC classes II , III , and IV.C.2 ) who had been diagnosed with major depressive disorder ( DSM-III-R ) . METHOD During a 7-week trial , patients were treated with fluoxetine 20 - 60 mg or placebo 1 - 3 capsules per day and were seen in weekly supportive group psychotherapy . In addition , subjects were rated on the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) , Clinical Global Impressions scales for Improvement ( CGI-I ) and Severity of Illness ( CGI-S ) , and the short version of the Beck Depression Inventory ( BDI-13 ) . Of the 47 patients enrolled in the study , 25 were administered fluoxetine and 22 were given placebo . RESULTS Subjects who received fluoxetine began to show significantly more improvement than patients who received placebo on both self- and observer-rated scales by the end of the first week of treatment . By endpoint , patients treated with fluoxetine experienced greater mean changes from baseline compared with placebo-treated patients on the HAM-D-17 ( 12.1 vs. 6.6 ; F = 6.53 , df = 1,45 ; p < .05 ) and BDI-13 ( 5.9 vs. 1.2 ; F = 5.73 , df = 1,45 ; p < .05 ) , and a greater percentage of fluoxetine-treated patients experienced a > or = 50 % in HAM-D-17 scores ( 64 % vs. 23 % ; chi2= 8.60 , df = 1 , p < .01 ) . Differences were particularly apparent in subjects whose initial depressive episodes were rated as severe ( i.e. , HAM-D-17 score > or = 24 ) . Severely depressed patients treated with fluoxetine had an endpoint CGI-I of 1.4 compared with an endpoint CGI-I of 2.7 for patients treated with placebo ( F = 6.02 , df = 1,11 ; p < .05 ) . Further , side effects were generally mild and transient . The most frequently noted effects reported by subjects treated with fluoxetine were nausea , dry mouth , headache , and diarrhea , in decreasing order of frequency . CONCLUSION This study supports the efficacy and safety of fluoxetine over and above group psychotherapy for the treatment of HIV-associated major depression This pilot study aim ed at fostering resilience among people living with HIV and improving the HIV-negative participants ’ acceptance of people living with HIV . A group of 75 people living with HIV who were former blood/plasma donors and 36 HIV-negative fellow villagers in rural China participated in the intervention . The 8 sessions lasted for 4 months and were facilitated by trained local family-planning officers . Efficacy of the intervention was assessed using a pre- and postprogram study design ; measurements were made at baseline , at completion , and 3 months afterward completion . The authors found that the HIV-positive participants increased their levels of resilience , social support , and quality of life and that they reported fewer symptoms of depression , anxiety , and stress at the completion of the intervention ; most of these changes were sustained at the 3-month follow-up . Such participants also reported subjective improvements on problem-solving skills , self-confidence , and a feeling of being cared for by others . In addition , the HIV-negative participants ’ discriminatory attitudes toward people living with HIV were reduced after completing the intervention . The majority of the participants was satisfied with the intervention and would recommend it to others . The train-the-trainer approach was used effectively . Positive effects of the intervention have been revealed and future r and omized controlled studies are warranted OBJECTIVE This study is a secondary analysis examining the effects of a cognitive-behavioral stress management ( CBSM ) intervention on indicators of positive psychological well-being and negative psychological well-being in HIV-positive racial/ethnic minority women at risk for cervical cancer due to human papillomavirus ( HPV ) infection and /or cervical intraepithelial lesions ( CIN ) . METHOD Racial/ethnic minority women with HIV and HPV and /or CIN I were r and omized to a 10-week CBSM group or a 1-day psychoeducational seminar . Participants completed a battery of measures of positive and negative psychological well-being at 3 time points : preintervention , 3 months postenrollment , and 9 months postenrollment . RESULTS Women in the CBSM group reported significant increases in domains of positive well-being , with no changes among women in the psychoeducational seminar , F(6 , 63 ) = 2.42 , p < .05 , η² = .19 . There were no significant changes in domains of negative well-being across time for either group , F(2 , 65 ) = 2.60 , p = .08 , η² = .07 . CONCLUSION These findings suggest that racial/ethnic minority women with HIV at risk for cervical cancer who were r and omized to a 10-week CBSM group experienced enhanced positive well-being . The lack of effects on negative well-being may be due to the relatively low levels of negative well-being present in this sample at study entry . Future research should examine whether these effects are replicated in a r and omized controlled trial of women with biopsy-confirmed CIN who present with greater distress levels that also employs a time-equivalent comparison condition Abstract This study explored the effects of cognitive-behavioral program ( CBP ) using a wait-list control group in 16 Chinese heterosexual HIV-infected men . Participants in the treatment condition underwent a 7-week group based CBP , which addressed various HIV-related issues . Relevant cognitive and behavioral strategies were taught as well . The aim of treatment was to improve the quality of life and to reduce psychological distress in a sample of heterosexual symptomatic HIV-infected men . Prior to intervention , baseline measures showed that our sample had a lower quality of life in comparison with the local general population . They also experienced a significant level of psychological distress . Following intervention , men in the CBP group demonstrated significant improvement in the mental health dimension of quality of life and a significant reduction in depressed mood . These preliminary findings suggested that short-term cognitive-behavioral therapy can be effective in improving the quality of life and mood of Chinese heterosexual HIV-infected men Objective To evaluate the immediate and long-term effectiveness of mindfulness-based stress reduction ( MBSR ) on biological and symptomatological markers of health among human immunodeficiency virus – positive ( HIV+ ) patients in Tehran , Iran . Methods Using a r and omized controlled trial design , data from 173 HIV+ patients ( CD4 count > 250 ) not yet receiving antiretroviral therapy , who participated in either an 8-week MBSR ( n = 87 ) or a brief education and support condition ( n = 86 ) at the Imam Khomeini Hospital , were analyzed . Assessment s included CD4 count , Symptom Checklist-90-Revised ( SCL-90R ) , and Medical Symptom Checklist ( MSCL ) at baseline , immediate post-treatment , and at the 3- , 6- , 9- , and 12-month follow-up periods . Results The treatment-adherent sample had a mean ( st and ard deviation ) age of 35.1 ( 6.5 ) years and 69 % were male . Linear mixed-model estimates indicated that , in the MBSR condition , the mean CD4 count increased from baseline up to 9 months after treatment and then returned to baseline level at 12 months . Improvements in mean SCL-90R ( up to 6 months ) and MSCL ( up to 12 months ) scores were observed for the MBSR condition , whereas education and support condition scores remained the same over time ; however , only MSCL improvements significantly differed between groups and these changes lasted up to the final assessment . Conclusions Findings suggest that among treatment-adherent Iranian HIV+ patients not yet receiving antiretroviral drug treatment , MBSR seems to have the strongest potential to improve self-reported medical symptoms . Trial Registration Iranian Registry of Clinical Trials : I RCT 201106084076N2 . Abbreviations HIV+ = human immunodeficiency virus – positive AIDS = acquired immune deficiency syndrome HAART = highly active antiretroviral therapy CD4 count = CD4 + T lymphocyte count MBSR = mindfulness-based stress reduction ESC = education and support condition SCL-90R = Symptom Checklist-90-Revised MSCL = Medical Symptom Abstract Though African American and Hispanic women accounted for 14 % of the female population in the USA , they represented 66 % of the total HIV/AIDS diagnoses among women in 2007 . Among men living with HIV , increased coping self-efficacy ( SE ) following a cognitive behavioral intervention has been related to decreased distress , anxiety , anger , and confusion , but comparable studies had not been carried out with HIV+ women . The purpose of this study was to examine the impact of changes in SE following a cognitive behavioral stress management plus expressive supportive therapy ( CBSM+ ) intervention on depression and anxiety in low-income urban predominantly minority women living with AIDS . Women ( n=451 ) were r and omized to a group CBSM+ or individual informational intervention condition and completed baseline , post-intervention and long-term follow-up ( 12 months ) assessment s of depression , anxiety and SE . Women who were assigned to the CBSM+ group condition and increased their level of cognitive behavioral SE reported significant decreases in anxiety and depression at post-intervention and long-term follow-up in comparison with controls who did not improve . Results suggest that both cognitive behavioral skills and a concomitant increase in the perceived level of SE in the use of those skills are predictive of distress reduction There is a lack of theory-based r and omized controlled trials to examine the effect of antiretroviral adherence in sub-Saharan Africa . We assessed the effectiveness of a lay health worker lead structured group intervention to improve adherence to antiretroviral therapy ( ART ) in a cohort of HIV-infected adults . This two-arm r and omized controlled trial was undertaken at an HIV clinic in a district hospital in South Africa . A total of 152 adult patients on ART and with adherence problems were r and omized 1:1 to one of two conditions , a st and ard adherence intervention package plus a structured three session group intervention or to a st and ard adherence intervention package alone . Self-reported adherence was measured using the Adult AIDS Clinical Trials Group adherence instrument prior to , post intervention and at follow-up . Baseline characteristics were similar for both conditions . At post-intervention , adherence information knowledge increased significantly in the intervention condition in comparison to the st and ard of care , while adherence motivation and skills did not significantly change among the conditions over time . There was a significant improvement in ART adherence and CD4 count and a significant reduction of depression scores over time in both conditions , however , no significant intervention effect between conditions was found . Lay health workers may be a useful adjunct to treatment to enhance the adherence information component of the medication adherence intervention , but knowledge may be necessary but not sufficient to increase adherence in this sample . Psychosocial informational interventions may require more advanced skill training in lay health workers to achieve superior adherence outcomes in comparison st and ard care in this re source -constrained setting |
12,909 | 29,746,721 | We found insufficient evidence to determine whether administration of melatonin would improve the quality and quantity of sleep in ICU patients . | BACKGROUND Patients in the intensive care unit ( ICU ) experience sleep deprivation caused by environmental disruption , such as high noise levels and 24-hour lighting , as well as increased patient care activities and invasive monitoring as part of their care .
Sleep deprivation affects physical and psychological health , and patients perceive the quality of their sleep to be poor whilst in the ICU .
Artificial lighting during night-time hours in the ICU may contribute to reduced production of melatonin in critically ill patients .
Melatonin is known to have a direct effect on the circadian rhythm , and it appears to reset a natural rhythm , thus promoting sleep .
OBJECTIVES To assess whether the quantity and quality of sleep may be improved by administration of melatonin to adults in the intensive care unit .
To assess whether melatonin given for sleep promotion improves both physical and psychological patient outcomes . | Introduction Many intensive care patients experience sleep disruption potentially related tonoise , light and treatment interventions . The purpose of this study was tocharacterise , in terms of quantity and quality , the sleep of intensive care patients , taking into account the impact of environmental factors . Methods This observational study was conducted in the adult ICU of a tertiary referralhospital in Australia , enrolling 57 patients . Polysomnography ( PSG ) was performedover a 24-hour period to assess the quantity ( total sleep time : hh : mm ) and quality ( percentage per stage , duration of sleep episode ) of patients ' sleep while in ICU.Rechtschaffen and Kales criteria were used to categorise sleep . Interrater checkswere performed . Sound pressure and illuminance levels and care events weresimultaneously recorded . Patients reported on their sleep quality in ICU using theRichards Campbell Sleep Question naire and the Sleep in Intensive Care Question naire . Data were summarised using frequencies and proportions or measures of central tendency and dispersion as appropriate and Cohen 's Kappa statistic wasused for interrater reliability of the sleep data analysis . Results Patients ' median total sleep time was 05:00 ( IQR : 02:52 to 07:14 ) . The majority ofsleep was stage 1 and 2 ( medians : 19 and 73 % ) with scant slow wave and REM sleep . The median duration of sleep without waking was 00:03 . Sound levels were high(mean Leq 53.95 dB(A ) during the day and 50.20 dB(A ) at night ) and illuminancelevels were appropriate at night ( median < 2 lux ) but low during the day(median : 74.20 lux ) . There was a median 1.7 care events/h . Patients ' meanself-reported sleep quality was poor . Interrater reliability of sleep staging washighest for slow wave sleep and lowest for stage 1 sleep . Conclusions The quantity and quality of sleep in intensive care patients are poor and may berelated to noise , critical illness itself and treatment events that disturb sleep . The study highlights the challenge of quantifying sleep in the critical care setting and the need for alternative methods of measuring sleep . The results suggest that a sound reduction program is required and other interventions toimprove clinical practice s to promote sleep in intensive care patients .Trial registration Australian New Zeal and clinical trial registry(http://www.anzctr.org.au/ ) : ACTRN12610000688088 Objective To assess survival , morbidity ( physical and psychological ) , quality of life ( QOL ) , and employment status of intensive care survivors up to 12 months after discharge from the intensive care unit ( ICU ) . Design Prospect i ve study . Setting University hospital adult ICU . Patients Between August 1 , 1995 , and July 31 , 1996 , 370 patients were admitted . Of these patients , 29 % died in the ICU . Three months after discharge from the ICU , 227 patients were alive , and 143 agreed to participate . Cumulative mortality was calculated using the original complete cohort . Measurements and Main Results Demographic data , severity of acute illness ( Acute Physiology and Chronic Health Evaluation [ APACHE ] II ) , admitting specialty , primary diagnosis , and length of stay were recorded . Physical and ICU-related psychological morbidity ( Hospital Anxiety and Depression scale score ) were recorded . Health-related QOL was assessed using the Short-Form 36 . All the question naires were completed in the clinic at 3 months . Assessment of physical morbidity and employment status at 6 and 12 months were conducted by telephone . The cumulative mortality was 39 % at 3 months , 41 % at 6 months , and 43 % at 12 months . Deaths after 3 months occurred in the group who refused follow-up . The median age for the follow-up group was 51 yrs ; the gender split was 68 women and 75 men ; the mean admission APACHE II score was 18.79 ( sd 6.15 ) ; and the median length of ICU stay was 3.8 days . At 3 months , ∼80 % of all patients interviewed were satisfied with their QOL . Older men ( > 65 yrs ) and younger women ( < 65 yrs ) demonstrated significantly better health with respect to some subdomains of the Short-Form 36 compared with their counterparts . The prevalence of psychological distress ( Hospital Anxiety and Depression scale score , ≥8 ) was low : 11.9 % had heightened anxiety , and 9.8 % were depressed . There were high levels of fatigue , poor concentration , and sleep disturbance ; the latter was more marked in women ( p = .022 ) . Improvement in all three symptoms occurred during the next 9 months . Significantly more women reported loss of hair ( p < .0001 ) . Men were slower to return to employment ; 75 % of women had returned by 6 months compared with only 65 % of men at 1 yr . Conclusion Assessment of outcome after ICU stay must include QOL measurements . Three months after discharge , there is a low incidence of ICU-related psychological or psychiatric illness and the majority of patients are satisfied . Differences in the incidence and nature of morbidity exist between the genders Background Delirium is an acute state of brain dysfunction characterised by fluctuating inattention and cognitive disturbances , usually due to illness . It occurs commonly in the intensive care unit ( ICU ) , and it is associated with greater morbidity and mortality . It is likely that disturbances of sleep and of the day-night cycle play a significant role . Melatonin is a naturally occurring , safe and cheap hormone that can be administered to improve sleep . The main aim of this trial will be to determine whether prophylactic melatonin administered to critically ill adults , when compared with placebo , decreases the rate of delirium . Methods This trial will be a multi-centre , r and omised , placebo-controlled study conducted in closed ICUs in Australia . Our aim is to enrol 850 adult patients with an expected ICU length of stay ( LOS ) of 72 h or more . Eligible patients for whom there is consent will be r and omised to receive melatonin 4 mg enterally or placebo in a 1:1 ratio according to a computer-generated r and omisation list , stratified by site . The study drug will be indistinguishable from placebo . Patients , doctors , nurses , investigators and statisticians will be blinded . Melatonin or placebo will be administered once per day at 21:00 until ICU discharge or 14 days after enrolment , whichever occurs first . Trained staff will assess patients twice daily to determine the presence or absence of delirium using the Confusion Assessment Method for the ICU score . Data will also be collected on demographics , the overall prevalence of delirium , duration and severity of delirium , sleep quality , participation in physiotherapy sessions , ICU and hospital LOS , morbidity and mortality , and healthcare costs . A subgroup of 100 patients will undergo polysomnographic testing to further evaluate the quality of sleep . Discussion Delirium is a significant issue in ICU because of its frequency and associated poorer outcomes . This trial will be the largest evaluation of melatonin as a prophylactic agent to prevent delirium in the critically ill population . This study will also provide one of the largest series of polysomnographic testing done in ICU.Trial registration Australian New Zeal and Clinical Trial Registry ( ANZCTR ) number : ACTRN12616000436471 . Registered on 20 December 2015 The Bispectral Index ( BIS ) is a system used to measure sedation levels . Some investigators recently analyzed changes in the BIS during natural sleep in adults and found that the BIS diminished considerably as sleep became deeper . No such studies have been undertaken to investigate changes in the BIS in sleeping children . The aim of this work was to assess the trend of the BIS in the various stages of sleep in a group of children , performing a descriptive analysis on a limited number of cases . We evaluated 15 children with negative clinical findings and a normal electroencephalogram ( EEG ) as part of their follow-up for prior episodes of epilepsy , recording the BIS and EEG in a waking state , in the various stages of sleep and on reawaking . For each stage , the mean value , the st and ard deviation , and the range of BIS values were calculated . The results showed that the BIS decreased progressively as sleep became deeper . The correlation between the stage of sleep and the BIS was significant . On reawaking , a slow increase was apparent in the BIS In this study , the aim was to test the biochemical effects of melatonin supplementation in Intensive Care Unit ( ICU ) patients , since their blood levels are decreased . Sixty-four patients were enrolled in the study . From the evening of the 3rd ICU day , patients were r and omized to receive oral melatonin ( 3 mg , group M ) or placebo ( group P ) twice daily , at 20:00 and 24:00 , until discharged . Blood was taken ( at 00:00 and 14:00 ) , on the 3rd ICU day to assess basal nocturnal melatonin values , and then during the treatment period on the 4th and 8th ICU days . Melatonin , total antioxidant capacity , and oxidative stress were evaluated in serum . Melatonin circadian rhythm before treatment was similar in the two groups , with a partial preservation of the cycle . Four hours from the 1st administration ( 4th ICU day , 00:00 ) , melatonin levels increased to 2514 ( 982.3 ; 7148 ) pg·mL−1 in group M vs. 20.3 ( 14.7 ; 62.3 ) pg·mL−1 in group P ( p < 0.001 ) . After five treatment days ( 8th ICU day ) , melatonin absorption showed a repetitive trend in group M , while in group P nocturnal secretion ( 00:00 ) was impaired : 20 ( 11.5 ; 34.5 ) pg·mL−1 vs. 33.8 ( 25.0 ; 62.2 ) on the 3rd day ( p = 0.029 ) . Immediately from the beginning of treatment , the total antioxidant capacity was significantly higher in melatonin treated subjects at 00:00 ; a significant correlation was found between total antioxidant capacity and blood melatonin values ( ρ = 0.328 ; p < 0.001 ) . The proposed enteral administration protocol was adequate , even in the early phase , to enhance melatonin blood levels and to protect the patients from oxidative stress . The antioxidant effect of melatonin could play a meaningful role in the care and well-being of these patients Background Sleep deprivation is common in critically ill patients in intensive care units ( ICU ) . It can result in delirium , difficulty weaning , repeated nosocomial infections , prolonged ICU length of stay and increased ICU mortality . Melatonin , a physiological sleep regulator , is well known to benefit sleep quality in certain people , but evidence for the effectiveness in ICU sleep disturbance is limited . Methods / Design This study has a prospect i ve , r and omized , double-blind , controlled , parallel-group design . Eligible patients are r and omly assigned to one of the two treatment study groups , labelled the ‘ melatonin group ’ or the ‘ placebo group ’ . A dose of 3 mg of oral melatonin or placebo is administered at 9:00 pm on four consecutive days . Earplugs and eye masks are made available to every participant . We plan to enrol 198 patients . The primary outcome is the objective sleep quality measured by the 24-hour polysomnography . The secondary outcomes are the subjective sleep quality assessed by the Richards Campbell Sleep Question naire , the anxiety level evaluated by the Visual Analogue Scale-Anxiety , the number of delirium-free days in 8 and 28 days , the number of ventilation-free days in 28 days , the number of antibiotic-free days , ICU length of stay , the overall ICU mortality in 28 days and the incidence and severity of the side effects of melatonin in ICU patients . Additionally , the body stress levels , oxidative stress levels and inflammation levels are obtained via measuring the plasma melatonin , cortisone , norepinephrine , malonaldehyde(MDA ) , superoxide dismutase(SOD ) , interleukin-6 ( IL-6 ) and interleukin-8 (IL-8)concentrations . Discussion The proposed study will be the first r and omized controlled study to use the polysomnography , which is the gold st and ard of assessing sleep quality , to evaluate the effect of melatonin on the sleep quality and circadian rhythms of ICU patients . The results may recommend a new treatment for ICU patients with sleep deprivation that is safe , effective and easily implementable in daily practice .Trial registration This study was registered with Clinical Trials ( NCT ; registration number : ChiCTR-TRC-14004319 ) on 4 March 2013 BACKGROUND AND AIM Patients in the intensive care unit often suffer from lack of sleep at night . We hypothesised that nocturnal melatonin may increase observed nocturnal sleep in tracheostomised patients . DESIGN Double-blind , r and omised , placebo-controlled pilot study . SETTING ICU of a tertiary hospital . PARTICIPANTS Thirty-two ICU patients with tracheostomy who were not receiving continuous sedation . METHODS We administered either oral melatonin ( 3 mg ) or placebo at 20:00 . We collected pre- and post-dosage blood sample s on Days 1 and 3 to confirm drug delivery . Primary outcome measure was number of hours of observed sleep at night , assessed by the bedside nurse . Secondary outcome measures included comparison of the incidence of agitation , assessed by score on the Riker Sedation-Agitation Scale , and requirement for sedatives or haloperidol to settle agitation . RESULTS Pre-treatment melatonin levels in the two groups were similarly low : 4.8 pg/mL ( 95 % CI , 2.4 - 7.5 ) for melatonin versus 2.4 ( 95 % CI , 1.6 - 3.2 ) for placebo ( P=0.13 ) . Post-treatment , melatonin levels increased significantly in the melatonin group compared with the placebo group ( 3543 pg/mL versus 3 pg/mL ; P<0.0001 ) . However , subsequent observed nocturnal sleep was similar in the two groups : 240 minutes ( range , 75 - 331.3 ) for melatonin v 243.4 minutes ( range , 0 - 344.1 ) for placebo ( P=0.98 ) . Observed diurnal sleep was also similar : 138.7 minutes ( range , 50 - 230 ) with melatonin v 104 minutes ( range , 0 - 485 ) for placebo ( P=0.42 ) . The incidence of agitation was non-significantly higher in the melatonin group ( 31 % v 7 % ; P=0.11 ) , while the requirement for extra sedation or use of haloperidol was slightly higher in the placebo group ( 57 % versus 46 % ; P=0.56 ) . CONCLUSION Melatonin is well absorbed , and a st and ard dose increases blood levels approximately 1000-fold . However , in this pilot assessment , these high levels failed to increase observed nocturnal sleep or induce other observable benefits in tracheostomised ICU patients Introduction Sleep disturbances are common in critically ill patients and when sleep does occur it traverses the day-night periods . The reduction in plasma melatonin levels and loss of circadian rhythm observed in critically ill patients receiving mechanical ventilation may contribute to this irregular sleep-wake pattern . We sought to evaluate the effect of exogenous melatonin on nocturnal sleep quantity in these patients and , furthermore , to describe the kinetics of melatonin after oral administration in this patient population , thereby guiding future dosing schedules . Methods We conducted a r and omised double-blind placebo-controlled trial in 24 patients who had undergone a tracheostomy to aid weaning from mechanical ventilation . Oral melatonin 10 mg or placebo was administered at 9 p.m. for four nights . Nocturnal sleep was monitored using the bispectral index ( BIS ) and was expressed in terms of sleep efficiency index ( SEI ) and area under the curve ( AUC ) . Secondary endpoints were SEI measured by actigraphy and nurse and patient assessment s. Plasma melatonin concentrations were measured in nine patients in the melatonin group on the first night . Results Nocturnal sleep time was 2.5 hours in the placebo group ( mean SEI = 0.26 , 95 % confidence interval [ CI ] 0.17 to 0.36 ) . Melatonin use was associated with a 1-hour increase in nocturnal sleep ( SEI difference = 0.12 , 95 % CI -0.02 to 0.27 ; P = 0.09 ) and a decrease in BIS AUC indicating ' better ' sleep ( AUC difference = -54.23 , 95 % CI -104.47 to -3.98 ; P = 0.04 ) . Results from the additional sleep measurement methods were inconclusive . Melatonin appeared to be rapidly absorbed from the oral solution , producing higher plasma concentrations relative to similar doses reported in healthy individuals . Plasma concentrations declined biexponentially , but morning ( 8 a.m. ) plasma levels remained supraphysiological . Conclusion In our patients , nocturnal sleep quantity was severely compromised and melatonin use was associated with increased nocturnal sleep efficiency . Although these promising findings need to be confirmed by a larger r and omised clinical trial , they do suggest a possible future role for melatonin in the routine care of critically ill patients . Our pharmacokinetic analysis suggests that the 10-mg dose used in this study is too high in these patients and may lead to carryover of effects into the next morning . Reduced doses of 1 to 2 mg could be used in future studies .Trial registration Current Controlled Trials IS RCT N47578325 Introduction Sleep deprivation is common in critically ill patients in the intensive care unit ( ICU ) . Noise and light in the ICU and the reduction in plasma melatonin play the essential roles . The aim of this study was to determine the effect of simulated ICU noise and light on nocturnal sleep quality , and compare the effectiveness of melatonin and earplugs and eye masks on sleep quality in these conditions in healthy subjects . Methods This study was conducted in two parts . In part one , 40 healthy subjects slept under baseline night and simulated ICU noise and light ( NL ) by a cross-over design . In part two , 40 subjects were r and omly assigned to four groups : NL , NL plus placebo ( NLP ) , NL plus use of earplugs and eye masks ( NLEE ) and NL plus melatonin ( NLM ) . 1 mg of oral melatonin or placebo was administered at 21:00 on four consecutive days in NLM and NLP . Earplugs and eye masks were made available in NLEE . The objective sleep quality was measured by polysomnography . Serum was analyzed for melatonin levels . Subjects rated their perceived sleep quality and anxiety levels . Results Subjects had shorter total sleep time ( TST ) and rapid eye movement ( REM ) sleep , longer sleep onset latency , more light sleep and awakening , poorer subjective sleep quality , higher anxiety level and lower serum melatonin level in NL night ( P < 0.05 ) . NLEE had less awakenings and shorter sleep onset latency ( P < 0.05 ) . NLM had longer TST and REM and shorter sleep onset latency ( P < 0.05 ) . Compared with NLEE , NLM had fewer awakenings ( P = 0.004 ) . Both NLM and NLEE improved perceived sleep quality and anxiety level ( P = 0.000 ) , and NLM showed better than NLEE in perceived sleep quality ( P = 0.01 ) . Compared to baseline night , the serum melatonin levels were lower in NL night at every time point , and the average maximal serum melatonin concentration in NLM group was significantly greater than other groups ( P < 0.001 ) . Conclusions Compared with earplugs and eye masks , melatonin improves sleep quality and serum melatonin levels better in healthy subjects exposed to simulated ICU noise and light . Trial registration Chinese Clinical Trial Registry ChiCTR-IPR-14005458 . Registered 10 November 2014 STUDY OBJECTIVES To objective ly measure sleep in critically ill patients requiring mechanical ventilation and to define selection criteria for future studies of sleep continuity in this population . DESIGN Prospect i ve cohort analysis . SETTING University teaching hospital medical-surgical ICU . PATIENTS Twenty critically ill ( APACHE II [ acute physiology and chronic health evaluation II ] acute physiology score [ APS ] , 10 + /- 5 ) , mechanically ventilated adults ( male 12 , female 8 , age 62 + /- 15 years ) with mild to moderate acute lung injury ( lung injury score , 1.8 + /- 0.9 ) 10 + /- 7 days after admission to the ICU . MEASUREMENTS AND RESULTS Patients were divided into three groups based on 24-h polysomnography ( PSG ) findings . No patient demonstrated normal sleep . In the " disrupted sleep " group ( n = 8) , electrophysiologic sleep was identified and was distributed throughout the day ( 6:00 AM to 10:00 PM ; 4.0 + /- 2.9 h ) and night ( 10:00 PM to 6:00 AM ; 3.0 + /- 1.9 h ) with equivalent proportions of non-rapid eye movement ( NREM ) and rapid eye movement ( REM ) sleep . Nocturnal sleep efficiency was severely reduced ( 38 + /- 24 % ) with an increased proportion of stage 1 NREM sleep ( 40 + /- 28 % total sleep time [ TST ] ) and a reduced proportion of REM sleep ( 10 + /- 14 % TST ) . Severe sleep fragmentation was reflected by a high frequency of arousals ( 20 + /- 17/h ) and awakenings ( 22 + /- 25/h ) . Electrophysiologic sleep was not identifiable in the PSG recordings of the remaining patients . These were classified either as " atypical sleep " ( n = 5 ) , characterized by transitions from stage 1 NREM to slow wave sleep with a virtual absence of stage 2 NREM and reduced stage REM sleep , or " coma " ( n = 7 ) , characterized by > 50 % delta or theta EEG activity with ( n = 5 ) and without ( n = 2 ) evidence of EEG activation either spontaneously or in response to deep painful stimuli . The combined atypical sleep and coma groups had a higher APS ( 13 + /- 4 vs 6 + /- 4 ) and higher doses of sedative medications than the disrupted sleep group . CONCLUSION Sleep , as it is conventionally measured , was identified only in a subgroup of critically ill patients requiring mechanical ventilation and was severely disrupted . We have proposed specific criteria to select patients for future studies to evaluate potential causes of sleep disruption in this population Purpose : Sleep deprivation may be particularly detrimental to intensive care unit ( ICU ) patients . Polysomnography has demonstrated abnormal sleep in medical and surgical ICU population s. Both environmental factors and circadian disruption have been implicated . We hypothesized that patients in a neurologic ICU would demonstrate similar sleep disturbances and that a combination of sleep-promoting interventions would increase sleep time . Methods : Twelve patients were enrolled in this pilot-r and omized , controlled , study in a neurologic ICU . For adult patients undergoing continuous EEG for clinical purpose s , noise-cancelling headphones and eye masks were worn , and an oral dose of melatonin was administered for 3 days , or until EEG was stopped . Sleep was scored according to st and ard criteria ; EEG was characterized and analyzed quantitatively . Results : Sixty-five percent of the patients ' recordings were unscorable based on accepted st and ardized criteria ; therefore , sleep measures could not be compared . For those with sleep that could be scored , total sleep time was normal , although sleep was fragmented and time spent in slow-wave or rapid eye movement sleep was notably decreased . Patients with unscorable recordings had worse injury severity measures , absent or significantly slower posterior dominant rhythm , and less coherence of posterior faster frequencies . Clinical outcomes were similar between intervention and control groups . Conclusions : Although sleep-promoting interventions were feasible , sleep quantification based on currently accepted criteria limited the ability to score sleep . Similar to other ICUs , sleep in the neurologic ICU is abnormal ; patients with unscorable sleep-like states have greater injury severity . This study was limited by strict enrollment criteria . A reliable method to quantify sleep and sleep-like states in the ICU is needed Disturbed sleep and sleep deprivation is common in patients in critical care setting s. Noise and inappropriate use of light/dark cycles are two of the causes of sleep interruptions . The purpose of the study was to evaluate eye masks and earplugs to help control patients ' exposure to noise and light within the critical care environment . An intervention study using a two group post-test quasi-experimental design of high dependency patients within a cardiothoracic critical care unit was undertaken by a group of critical care nurses . Sleep assessment rating scales and open-ended questions were used to obtain patients ' reported experiences of their sleep . Patients self-selected into either an intervention or non-intervention group . Sixty-four patients consented to take part in the study , 34 patients tried the interventions earplugs and eye masks and many found they improved sleep . However , noise was still a factor preventing sleep for both groups of patients . Mixed reports were found with the interventions from very comfortable to very uncomfortable . At a cost of 2.50 pounds sterling/patient , earplugs and eye masks were a relatively cheap intervention with notable improvements for some critically ill patients . Further research is required with a larger sample size , plus an examination of both earplugs and eye masks separately . Offering patient 's earplugs and eye masks to improve sleep should be considered as a matter of routine nursing practice , this should include time to show patients how to use and try them out for comfort BACKGROUND Critically ill patients suffer from physiological sleep deprivation and have reduced blood melatonin levels . This study was design ed to determine whether nocturnal melatonin supplementation would reduce the need for sedation in patients with critical illness . METHODS A single-center , double-blind r and omized placebo-controlled trial was carried out from July 2007 to December 2009 , in a mixed medical-surgical Intensive Care Unit of a University hospital , without any form of external funding . Of 1158 patients admitted to ICU and treated with conscious enteral sedation , 82 critically-ill with mechanical ventilation > 48 hours and Simplified Acute Physiology Score II>32 points were r and omized 1:1 to receive , at eight p.m. and midnight , melatonin ( 3 + 3 mg ) or placebo , from the third ICU day until ICU discharge . Primary outcome was total amount of enteral hydroxyzine administered . RESULTS Melatonin treated patients received lower amount of enteral hydroxyzine . Other neurological indicators ( amount of some neuroactive drugs , pain , agitation , anxiety , sleep observed by nurses , need for restraints , need for extra sedation , nurse evaluation of sedation adequacy ) seemed improved , with reduced cost for neuroactive drugs . Post-traumatic stress disorder prevalence did not differ between groups , nor did ICU or hospital mortality . Study limitations include the differences between groups before intervention , the small sample size , and the single-center observation . CONCLUSION Long-term enteral melatonin supplementation may result in a decreased need for sedation , with improved neurological indicators and cost reduction . Further multicenter evaluations are required to confirm these results with different sedation protocol Sleep deprivation is extremely common in the intensive care unit ( ICU ) , and this lack of sleep is associated with low melatonin secretion . The objective of the current study was to explore the effect of exogenous melatonin administration on sleep quality in patients hospitalized in the pulmonary intensive care unit ( ICU ) . We performed a double-blind , placebo-controlled study in the pulmonary ICU of a tertiary care hospital . Eight adult patients hospitalized in the pulmonary ICU with respiratory failure caused by exacerbation of chronic obstructive pulmonary disease ( COPD ) or with pneumonia were studied . Patients received either 3 mg of controlled-release melatonin or a placebo at 22:00 , and sleep quality was evaluated by wrist actigraphy . Treatment with controlled-release melatonin dramatically improved both the duration and quality of sleep in this group of patients . Our results suggest that melatonin administration to patients in intensive care units may be indicated as a treatment for sleep induction and resynchronization of the “ biologic clock . ” This treatment may also help in the prevention of the “ ICU syndrome ” and accelerate the healing process . ( Chronobiology International , 17(1 ) , 71–76 , 2000 Critically ill patients exhibit reduced melatonin secretion , both in nocturnal peaks and basal daytime levels . Oral melatonin supplementation may be useful for known sedative and antioxidant properties . Its early enteral absorption and daily pharmacokinetics were determined in two cohorts of six high-risk patients in this prospect i ve trial . During their third and fourth Intensive Care Unit ( ICU ) day , they underwent two different sets of repeated blood sample s to detect serum melatonin levels through radio-immuno-assay . Cohort 1 : sample s taken at 20:00 , 20:45 , 21:30 , 24:00 , 03:00 , 06:00 , 14:00 , 20:00 to describe the daily pharmacokinetics . Cohort 2 : 20:00 , 20:05 , 20:10 , 20:20 , 20:30 , 20:45 to study the early absorption . On ICU day 3 , endogenous levels were measured , while the absorption of exogenous melatonin was determined on ICU day 4 after administration , at 20:00 , of 3 mg melatonin . All basal levels were below the expected values . Following enteral administration , pharmacological levels were already reached in 5 min , with a serum peak after 16 min ( half-absorption time : 3 min 17 s ) . The maximum serum level observed was 11040 pg/mL and the disappearance rate indicated a half-elimination time of 1 hr 34 min . Serum melatonin levels decreased significantly after midnight ; pharmacological levels were maintained up to 10 hr following administration . No excessive sleepiness was reported in this patient group . Critically ill patients exhibited reduced melatonin secretion , as reported in the literature . Despite the critical illness , the oral bioavailability was satisfactory : serum levels after oral administration showed basically unchanged intestinal absorption , while disappearance rate was slower than reported elsewhere in healthy volunteers Abstract Background : Loss of circadian rhythms and reduced concentrations of endogenous melatonin are common in critically ill patients . After exogenous administration , supra-physiological concentrations in serum are only ephemeral , which may explain the absence of significant therapeutic effect on sleep . The aim of this study is to describe the pharmacokinetics of enteral melatonin in critically ill patients administered in a novel regimen aim ing to simulate endogenous release . Methods : Thirteen patients in the recovery phase of critical illness were r and omised to receive enteral melatonin or placebo . In the melatonin group , a total of 6 mg was administered as solution through their feeding tube , commencing with a 3 mg loading dose at 9 pm and six subsequent 0.5 mg doses hourly . The placebo was administered using a similar regimen . Serial blood sample s were taken and measured using a vali date d chromatographic method . The concentration-time data for serum melatonin concentrations were described using non-linear mixed-effects modelling . Results : The observed concentrations in the melatonin patients were significantly higher than that observed in the placebo patients . The concentrations in the patients administered melatonin were also higher than endogenous melatonin concentrations previously reported in non-critically ill patients . The patients administered melatonin had a mean clearance , volume of distribution and absorption rate constant of melatonin was 55.2 L/h , 767 L and 0.76 h–1 , respectively . Conclusions : Exogenous administration of melatonin with a loading dose of 3 mg followed by an hourly dose of 0.5 mg demonstrates good oral bioavailability and results in supra-physiological and sustained concentrations of serum melatonin during 12 h overnight |
12,910 | 22,956,190 | Conclusions Treatment with bisphosphonates reduced SREs , improved pain control , and showed a trend to increased survival . | Purpose Bisphosphonates are known to prevent skeletal-related events ( SREs ) in advanced breast cancer , prostate cancer , and multiple myeloma .
This systematic review assessed the efficacy of bisphosphonates in preventing SREs , controlling pain , and overall survival in patients with bone metastases from lung cancer . | PURPOSE We assessed the correlation of skeletal fracture with survival in men with prostate cancer on chronic and rogen suppressive therapy . MATERIAL S AND METHODS A total of 195 consecutive patients on chronic and rogen suppression for prostate cancer were evaluated for the history and type of skeletal fracture . Correlation with overall survival was performed via multivariate analysis . RESULTS Of these 195 men 24 reported skeletal fracture since the diagnosis of prostate cancer . Median overall survival was 121 and 160 months in men without and with a history of skeletal fracture since the diagnosis of prostate cancer , respectively ( p = 0.04 ) . A history of skeletal fracture was retained as a negative predictor of survival on forward stepwise regression analysis ( RR = 7.4 , p = 0.007 ) . CONCLUSIONS Our results suggest that skeletal fracture in patients with prostate cancer is an independent and adverse predictor of survival . Consideration for screening men at greatest risk via bone mineral density measurements and initiating empirical skeletal therapies ( bisphosphonates , estrogens and so forth ) may be warranted . This recommendation awaits validation through prospect i ve r and omized trials The results of a retrospective exploratory analysis of a phase III trial of zoledronic acid in patients with bone metastases secondary to lung cancer or other solid tumors are reported herein to assess the risk of skeletal-related events ( SREs ) and the efficacy of 4 mg zoledronic acid compared with placebo . The study is based on patient SRE history before study entry . Patients were stratified based on SRE history ( eg , pathologic fracture , spinal cord compression , radiation therapy or surgery to bone , or hypercalcemia ) before study entry , and SRE incidence over 21 months was analyzed . Of 507 patients r and omized to 4 mg zoledronic acid or placebo , 131 completed the 9-month core phase and 69 entered the 12-month extension phase . Before study entry , 347 of 503 patients who were evaluable for efficacy ( 69 % ) experienced > /= 1 SRE ; these patients had a higher risk of developing an SRE on study than patients with no prior SRE ( odds ratio , 1.41 ) . Among patients with an SRE before study entry , zoledronic acid reduced the risk of SREs by 31 % ( P = 0.009 ) , reduced the mean skeletal morbidity rate ( 1.96 vs. 2.81 SREs per year for placebo ; P = 0.030 ) , and prolonged the median time to first SRE by nearly 4 months ( 215 days vs. 106 days for placebo ; P = 0.011 ) . Among patients with no SRE before study entry ( n = 156 ) , zoledronic acid reduced the risk of SREs by 23 % ( P = 0.308 ) , reduced the mean skeletal morbidity rate ( 1.34 vs. 2.53 SREs per year for placebo ; P = 0.332 ) , and prolonged the median time to first SRE by 2.5 months ( P = 0.534 ) . This exploratory analysis demonstrates that patients with a history of SREs are at high risk for subsequent SREs , but zoledronic acid reduces skeletal morbidity regardless of SRE history This study was design ed to evaluate the efficacy and safety of combined zoledronic acid and docetaxel/carboplatin in patients with non-small cell lung cancer ( NSCLC ) as pre clinical studies showed synergistic antitumoral activity with bisphosphonates and docetaxel . Patients with inoperable stage IIIB or stage IV NSCLC were r and omized 2:1 to receive docetaxel 75mg/m(2 ) and carboplatin area under the concentration time curve 6 with ( Arm A ) or without ( Arm B ) zoledronic acid 4 mg every 3 weeks for 6 cycles . Patients responding in Arm A were rer and omized to receive monthly zoledronic acid ( maximum : 12 months [ Arm A1 ] or no zoledronic acid [ Arm A2 ] ) . Patients responding in Arm B entered Arm B1 for follow-up evaluation only . The primary endpoint was the proportion of patients without disease progression ; secondary endpoints were time to disease progression ( TTP ) , TTP in bone , best overall response rate , 1-year overall survival ( OS ) time , and safety ; study not powered to detect endpoint differences . Of 150 patients , 98 were r and omized to Arm A and 52 to Arm B. In the treatment phase , results were similar between groups in the proportion of patients without disease progression ( 40.9 % vs 38.8 % ; P=.8096 ) and median TTP ( 132d vs 132d ; P=.9622 ) . One-year OS times and best overall response rates were 266d vs 206d ( P=.4855 ) and 64.1 % vs 72 % ( P=.3423 ) , respectively ; the study was not powered to detect differences . In the follow-up phase , TTP and OS time were similar . Adding zoledronic acid to docetaxel/carboplatin in advanced stage NSCLC patients was well tolerated , but provided little to no effect on disease progression endpoints |
12,911 | 28,940,755 | There is no conclusive evidence regarding the effectiveness of supervised toothbrushing on caries incidence | BACKGROUND The anticaries effect of supervised toothbrushing , irrespective of the effect of fluoride toothpaste , has not been clearly determined yet .
AIM To assess the effects of supervised toothbrushing on caries incidence in children and adolescents . | OBJECTIVE This study assessed the percentage of the amount of dentifrice loaded onto the toothbrush that is ingested by children , taking into account age , the amount of dentifrice used during toothbrushing , and the dentifrice flavor . METHODS The sample consisted of 155 children of both genders attending public kindergartens and schools in Bauru , Brazil , divided into 5 groups ( n = 30 - 32 ) of children aged 2 , 3 , 4 , 5 and 6 years old . The dentifrices used were Sorriso ™ ( 1219 ppm F , peppermint-flavored ) and T and y ™ ( 959 ppm F , tutti-frutti-flavored ) . The assessment of fluoride intake from dentifrices was carried out six times for each child , using 0.3 , 0.6 , and 1.2 g of each dentifrice , following a r and om , crossover distribution . Brushing was performed by the children or their parents/caregivers according to the home habits and under the observation of the examiner . Fluoride present in the expectorant and on toothbrush was analyzed with an ion-specific electrode after HMDS-facilitated diffusion . Fluoride ingestion was indirectly derived . Results were analyzed by 3-way repeated- measures anova and Tukey 's tests ( P < 0.05 ) using the percent dentifrice ingested as response variable . RESULTS Age and percent dentifrice ingested for both dentifrices , and the three amounts used were inversely related ( P < 0.0001 ) . Percent dentifrice ingested was significantly higher after the use of T and y ™ under all conditions of the study when compared with Sorriso ™ ( P < 0.0001 ) . Significant differences were observed when brushing with 0.3 g when compared with 1.2 g , for both dentifrices tested ( P < 0.05 ) . CONCLUSIONS The results indicate that all variables tested must be considered in preventive measures aim ing to reduce the amount of fluoride ingested by young children 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. To investigate the effectiveness of 3 caries-preventive measures on high– and low – caries risk occlusal surfaces of first permanent molars over 3 y. This cluster-r and omized controlled clinical trial covered 242 schoolchildren , 6 to 7 y old , from low socioeconomic areas . At baseline , caries risk was assessed at the tooth surface level , through a combination of ICDAS II ( International Caries Detection and Assessment System ) and fissure depth codes . High – caries risk occlusal surfaces were treated according to daily supervised toothbrushing ( STB ) at school and 2 sealants : composite resin ( CR ) and atraumatic restorative treatment – high-viscosity glass-ionomer cement ( ART-GIC ) . Low – caries risk occlusal surfaces received STB or no intervention . Evaluations were performed after 0.5 , 1 , 2 , and 3 y. A cavitated dentine carious lesion was considered a failure . Data were analyzed according to the proportional hazard rate regression model with frailty correction , Wald test , analysis of variance , and t test , according to the jackknife procedure for calculating st and ard errors . The cumulative survival rates of cavitated dentine carious lesion – free , high – caries risk occlusal surfaces were 95.6 % , 91.4 % , and 90.2 % for STB , CR , and ART-GIC , respectively , over 3 y , which were not statistically significantly different . For low – caries risk occlusal surfaces , no statistically significant difference was observed between the cumulative survival rate of the STB group ( 94.8 % ) and the no-intervention group ( 92.1 % ) over 3 y. There was neither a difference among STB , CR , and ART-GIC on school premises in preventing cavitated dentine carious lesions in high – caries risk occlusal surfaces of first permanent molars nor a difference between STB and no intervention for low – caries risk occlusal surfaces of first permanent molars over 3 Children in the London Boroughs of Kensington , Chelsea and Westminster have one of the highest levels of caries in Engl and and Wales . In 1997/98 , the mean dmft for 5-year-old children was 2.83 with only 45.9 % of the children being caries free . The aim of this study was to determine whether teacher-supervised toothbrushing , once a day , at school , during term time , with commercial toothpaste containing 1,450 ppm fluoride , could reduce dental caries in primary school children when compared with children from the same community who did not receive this intervention . A total of 517 children ( mean age 5.63 years ) were recruited for the study . Class teachers were trained individually by the same dental hygienist in an appropriate toothbrushing technique for young children . Children in the intervention group brushed once a day at school . All examinations were by visual assessment only . All teeth present were assessed using the BASCD criteria . For children in the intervention group , the overall caries increment ( 2.60 ) was significantly less ( 10.9 % ; p < 0.001 ) than for children in the non-intervention group ( 2.92 ) . Among different tooth surfaces , the difference in caries increment between the intervention group ( 0.78 ) and the non-intervention group ( 1.03 ) was greatest for the proximal surfaces ( 21.4 % ; p < 0.01 ) . In conclusion , this study suggests that a programme of daily teacher-supervised toothbrushing with fluoride toothpaste can be effectively targeted into socially deprived communities and a significant reduction in dental caries can thereby be achieved especially among caries-susceptible children Objectives The aim of the study was to evaluate the effect of an intensified preventive programme in kindergartens . Material s and methods Two thous and two hundred twenty-eight 2- to 4-year-old children attending kindergartens in two counties in northern Hesse were r and omly allocated to two groups . Children in the test group participated in daily tooth brushing with 500 ppm fluoride toothpaste , which was supervised by specially trained dental nurses . Children in the control group received tooth brushing instructions three to four times a year . Caries experience was recorded using WHO criteria . The basic survey was performed from October 2006 to April 2007 , with the final examinations between March and July 2009 . The statistical evaluation was performed by means of the software package SPSS 17.0 . To compare the mean Δdmf values of the test and control groups , Mann-Whitney U tests were performed . Results Two thous and one hundred twelve children ( test group , 1096 ; control group , 1048 ) participated in the final examinations . The caries increment of the test group ( Δdmf-s = 1.55 ) was 24 % lower than the increment of the control group ( Δdmf-s = 2.02 , p = 0.043 ) . Based on Δdmf-t values , the corresponding figures were 0.79 for the test group and 1 for the control group ( p = 0.44 ) . High increment values ( Δdmf-s > 7 ) were observed in the control group twice as often as in the test group . Conclusion The results show that an intensified preventive programme in kindergartens , based on supervised daily tooth brushing , has a positive effect on the dental health of preschool children . Clinical relevance It is sufficient to offer such programmes in socially deprived areas Scottish children have one of the highest levels of caries experience in Europe . Only 33 % of 5-year-old children in Dundee who developed caries in their first permanent molars by 7 brushed their teeth twice a day . High-caries-risk children should benefit if they brush more often with fluori date d toothpaste . The aim of this clinical trial was to determine the reduction in 2-year caries increment that can be achieved by daily supervised toothbrushing on school-days with a toothpaste containing 1,000 ppm fluoride ( as sodium monofluorophosphate ) and 0.13 % calcium glycerophosphate , combined with recommended daily home use , compared to a control group involving no intervention other than 6-monthly clinical examinations . Five hundred and thirty-four children , mean age 5.3 , in schools in deprived areas of Tayside were recruited . Each school had two parallel classes , one r and omly selected to be the brushing class and the other , the control . Local mothers were trained as toothbrushing supervisors . Children brushed on school-days and received home supplies . A single examiner undertook 6-monthly examinations recording plaque , caries ( D1 level ) , and used FOTI to supplement the visual caries examination . For children in the brushing classes , the 2-year mean caries increment on first permanent molars was 0.81 at D1 and 0.21 at D3 compared to 1.19 and 0.48 for children in the control classes ( significant reductions of 32 % at D1 and 56 % at D3 ) . In conclusion , high-caries-risk children have been shown to have significantly less caries after participating in a supervised toothbrushing programme with a fluori date d toothpaste OBJECTIVES To evaluate the effect of a 2-year oral health education and caries prevention program implemented in kindergartens in China . METHODS Seven hundred and thirty-one 3-year-old children were recruited from 10 kindergartens in Miyun County , Beijing , China . The kindergartens were r and omly divided into two groups . Oral health education was provided to teachers in the test kindergartens every 3 months . Oral health education sessions were conducted for the test children monthly and for their parents semiannually . Children in the test kindergarten brushed their teeth twice daily with fluori date d toothpaste ( 1100 ppm F- ) in their kindergarten under the supervision of teachers during weekdays . No oral health education session and no supervised tooth brushing activities were carried out in the control kindergartens . A clinical examination of the study children and a question naire survey of their parents were conducted at baseline and after a 2-year program . RESULTS Five hundred and fourteen children remained in the study after 2 years . The mean caries increments of the test group ( n = 258 ) and the control group ( n = 256 ) were 2.47 and 3.56 dmfs , respectively . The reduction in dmfs increment was 30.6 % ( P = 0.009 ) . At the evaluation , a significantly higher percentage of children in the test group than in the control group reported brushing their teeth twice a day ( 87.6 % vs. 69.0 % ; P < 0.001 ) . Parents of children in the test group had better oral health knowledge and attitude than the parents of children in the control group . CONCLUSION This oral health education program was effective in establishing good oral health habits among preschool children and in increasing oral health knowledge of their parents , in conjunction with supervised daily tooth brushing with fluori date d toothpaste , which could reduce the development of new dental caries in preschool children in China |
12,912 | 28,608,597 | Episiotomy was more frequent in the h and s-on group ( average RR 0.58 , 95 % CI 0.43 to 0.79 , Tau² 0.07 , I² 74 % , four studies , 7247 women ; low- quality evidence ) , but there was considerable heterogeneity between the four included studies .There were no data for perineal trauma requiring suturing .
Other comparisonsThe delivery of posterior versus anterior shoulder first , use of a perineal protection device , different oils/wax , and cold compresses did not show any effects on perineal outcomes .
Moderate- quality evidence suggests that warm compresses , and massage , may reduce third- and fourth-degree tears but the impact of these techniques on other outcomes was unclear or inconsistent .
Poor- quality evidence suggests h and s-off techniques may reduce episiotomy , but this technique had no clear impact on other outcomes . | BACKGROUND Most vaginal births are associated with trauma to the genital tract .
The morbidity associated with perineal trauma can be significant , especially when it comes to third- and fourth-degree tears .
Different interventions including perineal massage , warm or cold compresses , and perineal management techniques have been used to prevent trauma .
This is an up date of a Cochrane review that was first published in 2011 .
OBJECTIVES To assess the effect of perineal techniques during the second stage of labour on the incidence and morbidity associated with perineal trauma . | BACKGROUND : The objective of the present study was to evaluate the effect of the two methods of delivery , “ h and s-on ” vs. “ h and s poised ” , on perineal trauma and delivery outcome in primiparous women referred to Shariati Hospital of Isfahan during 2007 - 2008 . METHODS : In a clinical trial study , 100 low risk primiparous pregnant women were r and omly assigned to two h and s-on and h and -poised ( h and s-off ) groups . In the h and s-on group , this method was used to control fetal head in the second stage of labor . It means that the fingers of one h and supported fetal occiput and the other h and applied slight pressure on the head to control the delivery of the head during the crowning process . In the h and s-poised group , midwife observed the parturient woman and do not touch perineum during the second labor stage while fetal head was delivering . Then , the two groups were compared in terms of perineal trauma , as well as neonatal and delivery outcome . RESULTS : Demographic characteristics of all studied women were similar in two groups . The rate of episiotomy was higher in h and s-on group ( 84 % vs. 40 % , p = 0.001 ) . The rate of postpartum hemorrhage ( 4th stage ) was higher in h and s-on group ( 12 % vs. 4 % , p = 0.04 ) . The rate of mild and moderate postpartum pain in h and s-on group was higher than h and s-off group ( 70 % vs. 58 % and 29 % vs. 10 % , p < 0.001 ) but sever pain was not different in two groups . CONCLUSIONS : It seems that h and s-poised method is associated with less perineal trauma , particularly regarding the lower need for episiotomy and postpartum hemorrhage OBJECTIVE To investigate the influence of the traditional h and s-on versus the innovative h and s-poised method on the risk of perineal trauma during vaginal delivery and on neonatal outcomes . STUDY DESIGN In a prospect i ve , r and omized , multicenter study , 1,161 of 1,505 women giving birth at the Departments of Obstetrics and Gynecology of the University Hospital of Vienna and Semmelweis Women 's Hospital , Vienna , between February and September 1999 , were r and omized into the trial . In the h and s-on method , the left h and of the midwife puts pressure on the infant 's head , and the right h and is placed against the perineum . In the h and s-poised method , the midwife guides the parturient through the birth without touching the perineum , prepared to apply light pressure on the infant 's head . RESULTS One hundred eighty-seven of 574 women ( 32.5 % ) in the h and s-on group and 180 of 502 women ( 35.8 % ) in the h and s-poised group experienced perineal tears ( P = .5 ) . Sixteen women ( 2.7 % ) treated with the h and s-on method developed third-degree perineal tears as compared with five women ( 0.9 % ) treated with the h and s-poised method ( P < .05 ) . In the h and s-on group , 103 women ( 17.9 % ) underwent episiotomy as compared with 51 cases ( 10.1 % ) in the h and s-poised group ( P < .01 ) . No significant differences in neonatal outcomes were observed between the two groups . CONCLUSION Our data suggest that a policy of h and s-poised care is more suitable for preserving the perineum during birth and is a safe and effective birthing alternative for women Summary Background The purpose of this study was to compare the obstetric outcome of low-risk maternity patients attended by certified midwives with that of low-risk maternity patients attended by obstetricians . Patients and methods Obstetric outcome of 1352 midwife patients was compared with that of 1352 age- and parity-matched physician patients with normal spontaneous vaginal delivery at the Department of Obstetrics and Gynecology of the University Hospital Vienna during the period from January 1997 to July 2002 . Our analysis was restricted to a sample of low-risk pregnant women . Women with medical or obstetric risk factors were excluded . Results A significant decrease in the use of oxytocin ( p=0.0001 ) was observed in women who selected a midwife as their primary birth attendant compared with women in the physician group . In both groups most women gave birth in a supine position ; however , significantly more alternative birth positions were used by midwife patients ( p=0.0001 ) . Concerning perineal trauma , a significantly lower rate of episiotomies ( p=0.0001 ) and perineal tears of all degrees ( p=0.006 ) were found in midwife patients . When analyzing severe postpartum hemorrhage and postpartum infections , there were no significant differences between the two groups ( p>0.05 ) . Concerning neonatal outcome , there were no significant differences in APGAR score < 7 at 5 minutes (p>0.05).Our data clearly show the ability of certified midwives to successfully provide prenatal care and delivery to lowrisk maternity patients , with neonatal outcomes comparable to those of physician patients . The use of certified midwives supervised by obstetricians may provide the optimum model for perinatal care , particularly for those women who are low-risk maternity patients , leaving physicians free to attend to the high-risk elements of care Background Whether certain birth positions are associated with perineal injuries and severe perineal trauma ( SPT ) is still unclear . The objective of this study was to describe the prevalence of perineal injuries of different severity in a low-risk population of women who planned to give birth at home and to compare the prevalence of perineal injuries , SPT and episiotomy in different birth positions in four Nordic countries . Methods A population -based prospect i ve cohort study of planned home births in four Nordic countries . To assess medical outcomes a question naire completed after birth by the attending midwife was used . Descriptive statistics , bivariate analysis and logistic regression were used to analyze the data . Results Two thous and nine hundred ninety-two women with planned home births , who birthed spontaneously at home or after transfer to hospital , between 2008 and 2013 were included . The prevalence of SPT was 0.7 % and the prevalence of episiotomy was 1.0 % . There were differences between the countries regarding all maternal characteristics . No association between flexible sacrum positions and sutured perineal injuries was found ( OR 1.02 ; 95 % CI 0.86–1.21 ) or SPT ( OR 0.68 ; CI 95 % 0.26–1.79 ) . Flexible sacrum positions were associated with fewer episiotomies ( OR 0.20 ; CI 95 % 0.10–0.54 ) . Conclusion A low prevalence of SPT and episiotomy was found among women opting for a home birth in four Nordic countries . Women used a variety of birth positions and a majority gave birth in flexible sacrum positions . No associations were found between flexible sacrum positions and SPT . Flexible sacrum positions were associated with fewer episiotomies Background : Many women suffer from perineal trauma during the normal vaginal delivery . Perineal trauma is mainly associated with pain and complications after the childbirth . Perineal management techniques can play a significant role in perineal trauma reduction . This study aim ed to compare the effects of perineal management techniques ( h and s-off technique , Ritgen maneuver and perineal massage using a lubricant during delivery ) on the labor complications . Material s and Methods : This quasi-experimental clinical trial was conducted on 99 primiparous women who referred to Daran Hospital , Isfahan , Iran for normal vaginal delivery in 2009 . The subjects were selected using a convenient method and r and omly assigned to three groups of Ritgen maneuver , h and s-off technique and perineal massage with lubricant . A question naire was used to determine the demographic characteristics of the participants and complications after birth . The short form of McGill Pain Question naire and the visual analogue scale for pain were also employed . The incidence and degree of perineal tears were evaluated immediately after delivery . Moreover , the incidence and severity of perineal pain were assessed 24 hours and also 6 weeks after delivery . Findings : In the Ritgen maneuver group , the frequency of tears , the relative frequency of tear degrees , the severity of perineal pain 24 hours after delivery and the frequency of pain and perineal pain severity 6 weeks after delivery were significantly different from the other two methods . Conclusions : H and s-off technique during parturition of the neonate 's head was associated with fewer complications after delivery . It was even better than perineal massage during the parturition OBJECTIVE The objective of the study was to determine whether bed delivery without stirrups reduces the incidence of perineal lacerations compared with delivery in stirrups . STUDY DESIGN In this r and omized trial , we compared bed delivery without stirrups with delivery in stirrups in nulliparous women . The primary outcome was any perineal laceration ( first through fourth degree ) . RESULTS One hundred eight women were r and omized to delivery without stirrups and 106 to stirrups . A total of 82 women r and omized to no stirrups ( 76 % ) sustained perineal lacerations compared with 83 in women allocated to stirrups ( 78 % ) ( P = .8 ) . There was no significant difference in the severity of lacerations or in obstetric outcomes such as prolonged second stage of labor , forceps delivery , or cesarean birth . Similarly , infant outcomes were unaffected . CONCLUSION Our results do not incriminate stirrups as a cause of perineal lacerations . Alternatively , our findings of no difference in perineal lacerations suggest that delivering in bed without stirrups confers no advantages or disadvantages Abstract Objective : Dianatal ® is a bioadhesive gliding film which reduces the opposing force to vaginal childbirth . We aim ed to investigate the safety , applicability , and impact of Dianatal ® obstetric gel on second stage of labor and perineal integrity . Methods : Low-risk singleton pregnancies at term were prospect ively enrolled . Eligible women were r and omly assigned to either labor management without using obstetric gel , or labor management using intermittent application of obstetric gel into the birth canal during vaginal examinations , starting at active phase of labor ( ≥4 cm dilation ) . The primary measured outcome was the length of second stage of labor . Results : Overall , 200 cases were analyzed . Demographic , obstetrical , and labor characteristics were similar between the groups . Neither adverse events nor maternal or neonatal side effects were observed . The mean lengths of the active and second stages of labor were comparable between the obstetric gel-treated and the control groups ( 157 versus 219 min and 48 versus 56 min , respectively ) . None of the women had grade III/IV perineal tears . Maternal and neonatal outcomes were not negatively influenced by using obstetric gel . No difference was found after sub-group analysis for spontaneous vaginal delivery . Conclusion : Dianatal ® obstetric gel is safe in terms of maternal or neonatal use . Albeit a trend toward shorter labor stages using Dianatal ® obstetric gel , no significant differences were noted among the groups . In order to further investigate the influence of the obstetric gel on labor stage interval , perineal integrity and maternal and neonatal outcomes , larger r and omized clinical trials are needed to be carried out BACKGROUND Trauma to the perineum is a serious and frequent problem after childbirth , with about 350000 women each year in the UK needing sutures for perineal injury after spontaneous vaginal delivery , and many millions more worldwide . We compared the continuous technique of perineal repair with the interrupted method , and the more rapidly absorbed polyglactin 910 suture material with the st and ard polyglactin 910 material . METHODS 1542 women who had a spontaneous vaginal delivery with a second-degree perineal tear or episiotomy were r and omly allocated to either the continuous ( n=771 ) or interrupted ( 771 ) suturing method , and to either the more rapidly absorbed polyglactin 910 suture material ( 772 ) or st and ard polyglactin 910 material ( 770 ) . Primary outcomes were pain 10 days after delivery and superficial dyspareunia 3 months postpartum . Analysis was by intention to treat . FINDINGS At day 10 , three women had dropped out of the study . Significantly fewer women reported pain at 10 days with the continuous technique than with the interrupted method ( 204/770 [ 26.5 % ] vs 338/769 [ 44.0 % ] , odds ratio 0.47 , 95 % CI 0.38 - 0.58 , p<0.0001 ) . Occurrence of pain did not differ significantly between groups assigned the more rapidly absorbed material or st and ard material ( 256/769 [ 33.3 % ] vs 286/770 [ 37.1 % ] , 0.84 , 0.68 - 1.04 , p=0.10 ) . Women reported no difference in superficial dyspareunia at 3 months for the continuous vs the interrupted method ( 98/581 [ 16.9 % ] vs 102/593 [ 17.2 % ] , 0.98 , 0.72 - 1.33 , p=0.88 ) or the more rapidly absorbed versus st and ard material ( 105/586 [ 17.9 % ] vs 95/588 [ 16.2 % ] , 1.13 , 0.84 - 1.54 , p=0.42 ) . Suture removal was done less with the more rapidly absorbed material than with st and ard suture material ( 22/769 [ 3 % ] vs 98/770 [ 13 % ] , p<0.0001 ) , and with the continuous versus interrupted method ( 24/770 [ 3 % ] vs 96/769 [ 12 % ] , p<0.0001 ) . INTERPRETATION A simple and widely practicable continuous repair technique can prevent one woman in six from having pain at 10 days . Also , the more rapidly absorbed polyglactin 910 material obviates need for suture removal up to 3 months postpartum for one in ten women sutured 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 Background Approximately 85 % of vaginal deliveries are accompanied by perineal trauma . The objective of this trial is to compare the incidence and degree of perineal trauma after primary delivery of the anterior compared with the posterior shoulder during vaginal birth . The hypothesis is that primary delivery of the posterior shoulder reduces the rate and degree of perineal trauma . Methods / design This is a single-centre , r and omized controlled trial , with computer-generated r and omization in a 1:1 allocation ratio . Women planning their first vaginal delivery ( n = 650 ) are r and omized to primary delivery of either the anterior or posterior shoulder . The primary outcome is any perineal trauma . Additional outcomes are the perineal injury subtypes , postpartum bleeding , umbilical artery pH , Apgar score at 5 minutes and any neonatal birth trauma . Perineal trauma is assessed by a midwife or doctor blinded to the method of shoulder delivery . All midwives are trained in the two methods of shoulder delivery and in the grading of perineal tears . The trial is being undertaken at a Danish community hospital with 1,600 yearly deliveries . Data will be analyzed according to the intention-to-treat principle . Recruitment started in January 2013 and the trial is planned to proceed for 24 months . Discussion Most delivery assistance techniques are based on tradition and heritage and lack objective evidence . This trial provides an example of how vaginal delivery techniques can be evaluated in a r and omized controlled trial . The results of this trial will clarify the role that delivery of the shoulders has on perineal trauma and thereby provide knowledge to recommendations on birthing technique . Trial registration Clinical Trials.gov : NCT01937546 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 Purpose Maintaining an intact perineum is a highly regarded aim in delivery procedures today . Since perineal massage is a common practice during delivery , the present study aims to investigate the effect of perineal massage with Vaseline on perineal trauma ( rate of episiotomy procedures and perineal tears ) . Method Ninety primiparous women ( aged between 18 and 30 years with gestational age of 38–42 weeks ) were selected sequentially in Tehran in 2009 . Once participants ’ characteristics were registered , they were r and omly assigned to the intervention ( perineal massage with Vaseline ) or control groups . In the massage group , perineal massage was performed in the second stage of delivery once the genitalia were treated with sterilized Vaseline . The perineum was examined after the delivery in terms of episiotomy or tear and its severity degree . Results The two groups were homogeneous in terms of demographic data , weight gain during pregnancy , gestational age , abortion history and fetal weight . The second stage of delivery was significantly shorter in the massage group than the control group and the massage group had significantly more intact perineum ( P = 0.004 ) . In addition , lower episiotomy and higher first- and second-degree perineal tears were seen in the massage group in comparison with the control one ( P < 0.001 ) . Neither of the groups suffered from third- and fourth-degree tears . Conclusion The findings showed that the perineal massage with Vaseline in the second stage of labor increases perineal integrity and decreases perineal traumas ( episiotomy and tears ) . So , it seems that the perineal massage could be an effective way to preserve an intact perineum in labor 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 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 Objective To evaluate the feasibility of a new technique of primary overlap anal sphincter repair instead Setting A teaching hospital and a district general hospital Introduction and hypothesisThe risk for urinary incontinence can be 2.6-fold greater in women after pregnancy and childbirth compared with their never-pregnant counterparts , with the incidence increasing with parity . We tested the hypothesis that the incidence of de novo postpartum urinary incontinence in primiparous women is reduced with the use of spontaneous pushing alone or in combination with perineal massage compared with women who experienced traditional directed pushing for second-stage management . Methods This was a prospect i ve clinical trial enrolling and r and omizing 249 women into a four-group design : ( 1 ) routine care with coached or directed pushing , ( 2 ) spontaneous self-directed pushing , ( 3 ) prenatal perineal massage initiated in the third trimester , and ( 4 ) the combination of spontaneous pushing plus perineal massage . Self-report of incontinence was assessed using analysis of variance ( ANOVA ) and covariance ( ANCOVA ) models in 145 remaining women at 12 months postpartum using the Leakage Index , which is sensitive to minor leakage . Results No statistical difference in the incidence of de novo postpartum incontinence was found based on method of pushing ( spontaneous/directed ) ( P value = 0.57 ) or in combination with prenatal perineal massage ( P value = 0.57 ) . Fidelity to pushing treatment of type was assessed and between-groups crossover detected . Conclusions Spontaneous pushing did not reduce the incidence of postpartum incontinence experienced by women 1 year after their first birth due to high cross-over between r and omization groups OBJECTIVE Our purpose was to compare consequences for women of receiving versus not receiving median episiotomy early and 3 months post partum on the outcomes perineal pain , urinary and pelvic floor functioning by electromyography , and sexual functioning and to analyze the relationship between episiotomy and third- and fourth-degree tears . STUDY DESIGN A secondary cohort analysis was performed of participants within a r and omized clinical trial , analyzed by type of perineal trauma and pain , pelvic floor , and sexual consequences of such trauma , while controlling for trial arm . The study was conducted in three university or community hospitals ; 356 primiparous and 341 multiparous women were studied . RESULTS Early and 3-month-postpartum perineal pain was least for women who gave birth with an intact perineum . Spontaneous perineal tears were less painful than episiotomy . Sexual functioning was best for women with an intact perineum or perineal tears . Postpartum urinary and pelvic floor symptoms were similar in all perineal groups . At 3 months post partum those delivered with an intact perineum had the strongest pelvic floor musculature , those with episiotomy the weakest . Among primiparous women third- and fourth-degree tears were associated with median episiotomy ( 46/47 ) . After forceps births were removed and 21 other variables potentially associated within such tears were controlled for , episiotomy was strongly associated with third- and fourth-degree tears ( odds ratio + 22.08 , 95 % confidence interval 2.84 to 171.53 ) . Physicians using episiotomy at high rates also used other procedures , including cesarean section , more frequently . CONCLUSION Perineal and pelvic floor morbidity was greatest among women receiving median episiotomy versus those remaining intact or sustaining spontaneous perineal tears . Median episiotomy was causally related to third- and fourth-degree tears . Those using episiotomy at the highest rates were more likely use other interventions as well . Episiotomy use should be restricted to specified fetal-maternal indications 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 Most of vaginal births are accompanied by lacerations in the genital tract . This was a r and omized study carried out in a Birth Center located in São Paulo city to evaluate the efficacy of liquid petroleum jelly in reducing perineal laceration . The sample was composed of 38 nulliparous women per group ( experimental and control ) . In the experimental group was used 30 ml of the petroleum jelly in the perineal region during the expulsive period . The parturient were allowed to push spontaneously during the delivery and remained in the left side position . The frequency of perineal laceration was similar in both groups ( experimental 63.2 % versus control 60.5 % ) . The posterior perineum region presented the highest frequency of trauma ( 53.2 % ) . Of the total cases of perineal trauma , 72.3 % were first-degree lacerations . The use of liquid petroleum jelly of perineal protection does not reduce the frequency neither the degree of lacerations in childbirth Abstract Objective : To determine the effects of perineal massage in the second stage of labour on perineal outcomes . Design : R and omised controlled trial . Participants : At 36 weeks ' gestation , women expecting normal birth of a singleton were asked to join the study . Women became eligible to be r and omised in labour if they progressed to full dilatation of the cervix or 8 cm or more if nulliparous or 5 cm or more if multiparous . 1340 were r and omised into the trial . Intervention : Massage and stretching of the perineum during the second stage of labour with a water soluble lubricant . Main outcome measures : Primary outcomes : rates of intact perineum , episiotomies , and first , second , third , and fourth degree tears . Secondary outcomes : pain at three and 10 days postpartum and pain , dyspareunia , resumption of sexual intercourse , and urinary and faecal incontinence and urgency three months postpartum . Results : Rates of intact perineums , first and second degree tears , and episiotomies were similar in the massage and the control groups . There were fewer third degree tears in the massage group ( 12 ( 1.7 % ) v 23 ( 3.6 % ) ; absolute risk 2.11 , relative risk 0.45 ; 95 % confidence interval 0.23 to 0.93 , P<0.04 ) , though the trial was underpowered to measure this rarer outcome . Groups did not differ in any of the secondary outcomes at the three assessment points . Conclusions : The practice of perineal massage in labour does not increase the likelihood of an intact perineum or reduce the risk of pain , dyspareunia , or urinary and faecal problems . What is already known on this topic Perineal trauma during vaginal birth and its sequelae , including urinary and faecal incontinence , dyspareunia , and persistent pain , have a negative impact on the sexuality , self esteem , and quality of life of countless women each year Perineal massage conducted antenatally has some benefit in reducing the risk of perineal trauma Perineal massage in the second stage of labour has been promoted and practised without sound evidence of its effectiveness What this study adds Perineal massage in the second stage of labour did not have any effect on the likelihood of an intact perineum , perineal trauma , pain , or subsequent sexual , urinary or faecal outcomes but was not harmful The results support midwives in following their usual practice while taking account of the preferences of individual BACKGROUND Anal incontinence is an embarrassing condition that is largely underreported . Obstetric anal sphincter injuries are the major etiological factor . Recognition of risk factors may minimize the development of sphincter injuries . The objective of this study was to identify risk factors for sphincter injuries and measure dimensions of mediolateral episiotomies . METHODS Women expecting their first vaginal delivery were invited to participate , and an experienced research fellow performed a perineal and rectal examination and classified tears according to the new international classification . Dimensions of episiotomies were measured and obstetric variables recorded prospect ively . RESULTS Of the 241 women recruited , 59 ( 25 % ) sustained sphincter injuries . Univariate analysis revealed that forceps delivery OR 4.03 ( 1.63 - 9.92 ) , vacuum extraction OR 2.64 ( 1.25 - 5.54 ) , gestation > 40 weeks OR 3.18 ( 2.35 - 4.29 ) , and mediolateral episiotomy OR 5.0 ( 2.64 - 9.44 ) were associated with these injuries . In addition , compared with women who had no injuries , sphincter injuries were more common with higher birthweight ( 3.51 vs 3.17 kg , p < 0.01 ) , larger head circumference ( 34.3 vs 33.3 cm , p < 0.01 ) , and longer second stage of labor ( 76 vs 51 min , p < 0.01 ) . Multiple logistic regression revealed higher birthweight and mediolateral episiotomy OR 4.04 ( 1.71 - 9.56 ) as independent risk factors . Episiotomies angled closer to the midline were significantly associated with such injuries ( 26 vs 37 degrees , p = 0.01 ) . No midwife and only 13 ( 22 % ) doctors performed truly mediolateral episiotomies . CONCLUSIONS Mediolateral episiotomy is an independent risk factor for anal sphincter injuries . Although a liberal policy of mediolateral episiotomy does not appear to reduce the risk of such injuries , it may be related to inappropriate technique . A concerted approach to educate trainees in appropriate episiotomy technique and identification of sphincter injuries is imperative to enable reexamination of the true merits or disadvantages of mediolateral episiotomy OBJECTIVE Postpartum perineal pain and dyspareunia have been reported to affect 42 % of women within the first 2 weeks after their first vaginal delivery . We aim ed to determine the prevalence of dyspareunia and perineal pain using vali date d pain scores following accurate classification of perineal trauma according to the guidelines of the Royal College of Obstetricians and Gynaecologists . STUDY DESIGN Prospect i ve study of women having their first vaginal delivery . All women had a perineal and rectal examination . Pain was assessed with a 4-point Verbal Rating Score and an 11-point visual analogue scale on day 1 , day 5 and 2 months after delivery . RESULTS Two hundred and fifty-four women were invited and 95 % participated . Ninety-two percent experienced perineal pain on day one , resolving in 88 % ( p<0.001 ) at 2 months . Compared to an intact perineum or first degree tear significantly more women experienced perineal pain after a second , third or fourth degree tear . Forty percent resumed coitus within 2 months regardless of whether perineal trauma occurred or not . Five days after delivery , uncomplicated episiotomies result ed in more perineal pain than second degree tears . CONCLUSIONS Although perineal pain affected 92 % of mothers , it resolved in the majority within 2 months of delivery . Obstetric anal sphincter injury is associated with more perineal pain than other perineal trauma . Spontaneous second degree tears cause less perineal pain than episiotomies . The 11-point visual analogue scale may be more sensitive than the 4-point Verbal Rating Score OBJECTIVES The purpose of this study was to determine the frequency of perineal pain in the 6 weeks after vaginal delivery and to assess the association between perineal trauma and perineal pain . Study design This was a prospect i ve cohort study of parturients at 1 day , 7 days , ' and 6 weeks ' post partum in an academic tertiary obstetric unit in Toronto , Canada . Four hundred forty-four women were followed up , including women with an intact perineum ( n=84 ) , first-/second-degree tears ( n=220 ) , episiotomies ( n=97 ) , or third-/fourth-degree tears ( n=46 ) . Primary outcome was the incidence of perineal pain on day of interview ; secondary outcomes were pain score measurements and interference with daily activities . RESULTS Perineal trauma was more common among primiparous women , those with operative vaginal deliveries , and those with epidural analgesia during the second stage of labor . The incidence of perineal pain among the groups during the first week was intact perineum 75 % ( day 1 ) and 38 % ( day 7 ) ; first-/second-degree tears 95 % and 60 % ; episiotomies 97 % and 71 % ; and third-/fourth-degree tears 100 % and 91 % . By 6 weeks , the frequency of perineal pain was not statistically different between trauma groups . CONCLUSION Acute postpartum perineal pain is common among all women . However , perineal pain was more frequent and severe for women with increased perineal trauma OBJECTIVES To describe the postpartum perineal morbidity of primiparous women who had a vaginal birth and compare outcomes between Asian and non-Asian women in the first 2 days following the birth and at 6 and 12 weeks postpartum . DESIGN Data from a r and omized clinical trial of a perineal management technique ( perineal warm packs ) were used to address the study objective . SETTING Two maternity hospitals in Sydney , Australia . PARTICIPANTS Primiparous women who had a vaginal birth in the trial were included ( n=697 ) . One third of the women were identified as " Asian . " RESULTS Compared with non-Asian women , Asian women were significantly more likely to have an episiotomy ; require perineal suturing ; sustain a third- or fourth-degree perineal tear ; and report their perineal pain as being moderate to severe on day 1 following the birth . Asian women were less likely to give birth in an upright position or to resume sexual intercourse by 6 or 12 weeks following the birth . CONCLUSION More research is needed into methods that could reduce the high rates of perineal trauma experienced by Asian women , and midwives need to be able to offer appropriate support for Asian women Abstract Objective : To determine whether perineal massage during the second stage of labor using oil enriched with vitamins , increases the chances of delivering with an intact perineum as compared to perineal massage using pure liquid wax . Method : A prospect i ve , r and omized , double-blind study was conducted . Women were assigned to liquid wax ( jojoba oil ) versus purified formula of almond and olive oil , enriched with vitamin B1 , B2 , B6 , E and fatty acids . The caregivers used the oils during the second stage of labor . Results : A total of 164 women undergoing vaginal delivery were recruited . No significant differences regarding perineal lacerations , number of sutures and length of suturing were noted between the two groups . Likewise , while analyzing separately nulliparous and multiparous women , no significant differences were noted . Controlling for birth weight > 4000 g , using the Mantel – Haenszel technique , no association was noted between perineal lacerations and the type of oil used ( weighted OR = 0.9 , 95 % CI 0.3–2.4 ; p = 0.818 ) . Conclusion : The type of the oil used during the second stage of labor for prevention of perineal tears has no effect on the integrity of the perineum . Accordingly , it seems that there is no perfect oil Objective To compare , in a prospect i ve , r and omised controlled trial , differences in anal sphincter function following forceps or vacuum assisted vaginal delivery in an institution practising st and ardised management of labour Abstract Objective : To determine whether the obstetric gel shortens the second stage of labor and exerts a protective effect on the perineum . Method : A total of 251 nulliparous women with singleton low-risk pregnancies in vertex position at term were recruited . A total of 228 eligible women were r and omly assigned to Group A , without obstetric gel use , or to Group B , obstetric gel use , i.e. , intermittent application into the birth canal during vaginal examinations , starting at the early first stage of labor ( prior to 4 cm dilation ) and ending with delivery . Results : A total of 183 cases were analyzed . For vaginal deliveries without interventions , such as C-section , vaginal operative procedure or Kristeller maneuver , obstetric gel use significantly shortened the second stage of labor by 26 min ( 30 % ) ( P=0.026 ) , and significantly reduced perineal tears ( P=0.024 ) . First stage of labor and total labor duration were also shortened , but not significantly . Results did not show a significant change in secondary outcome parameters , such as intervention rates or maternal and newborn outcomes . No side effects were observed with obstetric gel use . Conclusion : Systematic vaginal application of obstetric gel showed a significant reduction in the second stage of labor and a significant increase in perineal integrity . Future studies should further investigate the effect on intervention rates and maternal and neonatal outcome parameters Objective To prospect ively assess change in bowel symptoms and quality of life ( QoL ) approximately 3 years after primary repair of obstetric anal sphincter injuries ( OASIS ) . Methods Between July 2002 and December 2007 women who attended the perineal clinic at Croydon University Hospital , UK , 9 weeks following primary repair of OASIS were asked to complete the Manchester Health Question naire and a question naire to obtain a St Mark incontinence score . All women had endoanal scans at this visit . In June 2008 all women were asked to complete the question naires again . Results Of 344 patients who responded to the question naires and were included in the analysis , long-term symptoms of fecal urgency , flatus incontinence , and fecal incontinence occurred in 62 ( 18.0 % ) , 52 ( 15.1 % ) , and 36 ( 10.5 % ) , respectively . Overall , there was a significant improvement in fecal urgency ( P < 0.001 ) and flatus incontinence ( P < 0.001 ) from 9 weeks to 3 years . Of 31 women with fecal incontinence symptoms at early follow-up , 28 were asymptomatic at 3 years . However , 33 women developed de novo symptoms . The only predictors of fecal incontinence at 3 years were fecal urgency at 9 weeks ( OR 4.65 ; 95 % CI , 1.38–15.70 ) and a higher St Mark score ( OR 1.40 ; 95 % CI , 1.09–1.80 ) . Conclusion Following primary repair of OASIS , the majority of symptoms and QoL significantly improve , unless there is a persistent anal sphincter defect . This highlights the importance of adequate repair Background . Pushing in the second stage of labor can be forced or follow the spontaneous urge to bear down . Recent studies have shown that spontaneous pushing results in a longer second stage , fewer CTG changes , higher arterial pH and less damage to the birth canal . Method . R and omized trial of spontaneous vs. forced pushing in 350 primiparous women . Results . There was no difference between the r and omized groups in duration of second stage of labor , umbilical arterial pH or damage to the birth canal . Of the women allotted to spontaneous pushing , 65.6 % used the closed glottis technique for more than half the expulsive phase . When dividing the women into two groups according to the actual pushing technique used most , open or closed glottis , it turned out that women who used the open glottis technique had a shorter second stage of labor and gave birth to infants with lower birth weight Objective The objective of the current study was to compare the “ H and s-off ” and “ H and s-on ” methods to reduce perineal lacerations . Method We conducted a r and omized controlled trial to compare the effectiveness of two techniques for perineum protection during spontaneous delivery . Study participants included 600 nulliparous expectant mothers , who were divided equally between the “ h and s off ” and “ h and s on ” groups ( n_300 per group ) . Findings A total of 147 ( 49 % ) women in the “ H and s-on ” and 143 women ( 47.7 % ) in the “ H and -off ” groups encountered perineal trauma ( p = 0.74 ) . In the “ H and s-on ” group , 8 women ( 2.7 % ) experienced a third degree trauma compared with ( 0.3 % ) that in the “ H and s-off ” method ( p = 0.1).Episiotomy was performed on 38 women ( 12.7 % ) from the “ H and s-on ” and 17 ( 5.7 % ) women from the “ H and s-off ” ( p = 0.003 ) groups . In addition , 28 women ( 9.3 % ) from the “ H and s-on ” group and 47 women ( 15.7 % ) from the “ H and s-off ” group experienced periurethral tears ( p = 0.01 ) that did not need mending . Conclusion Application of the “ H and s-off ” method for vaginal delivery has a positive effect on the mother ’s health because of the reduction of Episiotomy and third degree tearing . Therefore , we conclude that the “ H and s-off ” method offers a safer alternative for perineal control during labor Genital tract trauma after spontaneous vaginal childbirth is common , and evidence -based prevention measures have not been identified beyond minimizing the use of episiotomy . This study r and omized 1211 healthy women in midwifery care at the University of New Mexico teaching hospital to 1 of 3 care measures late in the second stage of labor : 1 ) warm compresses to the perineal area , 2 ) massage with lubricant , or 3 ) no touching of the perineum until crowning of the infant 's head . The purpose was to assess whether any of these measures was associated with lower levels of obstetric trauma . After each birth , the clinical midwife recorded demographic , clinical care , and outcome data , including the location and extent of any genital tract trauma . The frequency distribution of genital tract trauma was equal in all three groups . Individual women and their clinicians should decide whether to use these techniques on the basis of maternal comfort and other considerations Objective . Maternal lifestyle factors are potential predictors of pregnancy complications . We examined relations between modifiable factors and delivery complications . Design . Prospect i ve cohort . Setting . University hospital antenatal clinic , Oslo , Norway . Sample . A cohort of 553 women followed through pregnancy and delivery . Main outcome measures . Pre‐specified birth complications : cesarean section ( CS ) , operative vaginal deliveries ( VDs ) , third and fourth degree of perineal lacerations and hemorrhage ( ≥1,000 ml ) . Methods . Univariate and multiple logistic regression analyses were performed . Besides high birthweight ( ≥4,200 g ) , modifiable predictors ( high body mass index ( BMI ) , fasting glucose and physical inactivity ) and non‐modifiable predictors ( parity , maternal age , gestational age , and gender ) were considered . Results . Significant predictors for induction of labor were parity ( odds ratio ( OR ) : 2.1 ; 95 % CI 1.3–3.5 ) , maternal age ( OR : 2.0 ; 1.2–3.4 ) , gestational age ( OR : 1.9 ; 1.1–3.1 ) , and BMI ≥30 ( OR : 4.2 ; 2.2–7.8 , p<0.01 ) . High birthweight and high BMI were overrepresented among CSs . Emergency CS was associated with birthweight ( OR : 3.7 ; 1.7–8.1 ) , parity ( OR : 3.5 ; 1.7–7.2 ) , maternal age ( OR : 2.6 ; 1.3–5.3 ) , and induction of labor ( OR : 4.8 ; 2.6–9.1 ) . After excluding CS , operative VD was associated with parity ( OR : 8.7 ; 3.8–20 ) and gender ( OR : 2.2 ; 1.2–14.1 ) . Perineal laceration was associated with pre‐gestational physical inactivity ( OR : 6.1 ; 1.6–22.9 ) and operative VD ( OR : 5.1 ; 1.5–17.6 ) . Hemorrhage was associated with high birthweight ( OR : 4.2 ; 1.2–4.7 ) and BMI ≥30 ( OR : 4.6 ; 1.2–17.7 ) . Conclusions . Pre‐gestational physical inactivity increased the risk of perineal lacerations and male infants were associated with higher risk of vaginal operative delivery BACKGROUND Our purpose was to assess benefits and possible disadvantages of water births and to compare maternal and neonatal outcomes with normal vaginal deliveries . METHODS This case-controlled study was carried out between January 2000 and July 2001 . A total of 140 women who wanted water births were enrolled into the study . Our analysis was restricted to a sample of women with a gestational age > 37 weeks , a normal sized foetus , a reactive admission cardiotocography , drainage of clear amniotic fluid ( if the membranes were already ruptured ) and a pregnancy with cephalic presentation . Women with medical or obstetric risk factors were excluded . 140 controls were selected from the delivery data base as the next parity-matched normal spontaneous vaginal delivery . RESULTS A statistically significant lower rate of episiotomies ( p = 0.0001 ) and vaginal trauma ( p = 0.03 ) was detected in the group assigned to water birth , whereas the frequency of perineal tears and labial trauma remained similar in both groups ( p > 0.05 ) . A statistically significant decrease in the use of medical analgesia ( p = 0.0001 ) and oxytocin ( p = 0.002 ) was observed in women who had water births . A trend towards a reduction of the length of the first stage of labour was only observed in primiparous women bearing in water , but this reduction did not reach statistically significance ( p > 0.05 ) . Manual placenta removal ( p = 0.017 ) , severe postpartum haemorrhage ( blood loss > 500 ml ; p = 0.002 ) and maternal infection rate ( p = 0.03 ) were statistically significant lower in women who delivered in water . When analysing the postpartum haemoglobin , no statistically significant differences could be observed between the two groups ( p > 0.05 ) . No statistically significant differences were detected for neonatal parameters ( p > 0.05 ) between women who had had water births and those choosing conventional vaginal delivery OBJECTIVE : To investigate whether Ritgen ’s maneuver decreases the risk of third- to fourth-degree perineal tears compared with simple perineal support . METHODS : A total of 1,623 nulliparous women in term labor , singleton pregnancy , and cephalic presentation were r and omly assigned to Ritgen ’s maneuver or st and ard care . Ritgen ’s maneuver denotes extracting the fetal head , using one h and to pull the fetal chin from between the maternal anus and the coccyx , and the other on the fetal occiput to control speed of delivery . Ritgen ’s maneuver was performed during a uterine contraction , rather than , as originally recommended , between contractions . Our st and ard care entailed perineal support with one h and and control of the speed of crowning with the other , and use of Ritgen ’s maneuver only on specific indications . Women delivered by cesarean delivery ( n=10 ) or instrumentally ( n=142 ) were excluded , as well as 39 erroneously included women ( parous or in preterm labor ) , six inaccurately assigned participants , one with missing data , and two participants who withdrew consent . For the remaining 1,423 women , the result was analyzed according to intention to treat . RESULTS : Ritgen ’s maneuver was performed in 554 ( 79.6 % ) of 696 women r and omly assigned to this procedure and in 31 ( 4.3 % ) of 727 women r and omly assigned to simple perineal support . The rate of third- to fourth-degree tears was 5.5 % ( n=38 ) in women assigned to Ritgen ’s maneuver and 4.4 % ( n=32 ) in those assigned to simple perineal support ( relative risk 1.24 ; 95 % confidence interval 0.78–1.96 ) . CONCLUSION : Ritgen ’s maneuver does not decrease the risk of anal sphincter injury at delivery , at least not when performed during a contraction . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00652977 LEVEL OF EVIDENCE : BACKGROUND Incontinence of stool and flatus are frequent complications of childbirth . We examined the prevalence and possible causes of these adverse outcomes in a large cohort of women . METHODS We studied 949 pregnant women who gave birth in 5 hospitals in 1995/96 in the province of Quebec . These women , participants in a r and omized controlled trial of prenatal perineal massage , completed a self-administered question naire 3 months after giving birth . RESULTS Three months after delivery 29 women ( 3.1 % ) reported incontinence of stool , and 242 ( 25.5 % ) had involuntary escape of flatus . Incontinence of stool was more frequent among women who delivered vaginally and had third- or fourth-degree perineal tears than among those who delivered vaginally and had no anal sphincter tears ( 7.8 % v. 2.9 % ) . Forceps delivery ( adjusted risk ratio [ RR ] 1.45 , 95 % confidence interval [ CI ] 1.01 - 2.08 ) and anal sphincter tears ( adjusted RR 2.09 , 95 % CI 1.40 - 3.13 ) were independent risk factors for incontinence of flatus or stool or both . Anal sphincter injury was strongly and independently associated with first vaginal birth ( RR 39.2 , 95 % CI 5.4 - 282.5 ) , median episiotomy ( adjusted RR 9.6 , 95 % CI 3.2 - 28.5 ) , forceps delivery ( adjusted RR 12.3 , 95 % CI 3.0 - 50.4 ) and vacuum-assisted delivery ( adjusted RR 7.4 , 95 % CI 1.9 - 28.5 ) but not with birth weight ( adjusted RR for nirth weight 4000 g or more : 1.4 , 95 % CI 0.6 - 3.0 ) or length of the second stage of labour ( adjusted RR for second stage 1.5 hours or longer compared with less than 0.5 hours : 1.2 , 95 % CI 0.5 - 2.7 ) . INTERPRETATION Anal incontinence is associated with forceps delivery and anal sphincter laceration . Anal sphincter laceration is strongly predicted by first vaginal birth , median episiotomy , and forceps or vacuum delivery but not by birth weight or length of the second stage of labour OBJECTIVE to determine women 's and midwives ' experiences of using perineal warm packs in the second stage of labour . DESIGN as part of a r and omised controlled trial ( Warm Pack Trial ) , women and midwives were asked to complete question naires about the effects of the warm packs on pain , perineal trauma , comfort , feelings of control , satisfaction and intentions for use during future births . SETTING two hospitals in Sydney , Australia . PARTICIPANTS a r and omised controlled trial was undertaken . In the late second stage of labour , nulliparous women ( n=717 ) giving birth were r and omly allocated to having warm packs ( n=360 ) applied to their perineum or st and ard care ( n=357 ) . St and ard care was defined as any second stage practice carried out by midwives that did not include the application of warm packs to the perineum . Three hundred and two nulliparous women r and omised to receive warm packs ( 84 % ) received the treatment . Question naires were completed by 266 ( 88 % ) women who received warm packs , and 270 ( 89 % ) midwives who applied warm packs to these women . INTERVENTION warm , moist packs were applied to the perineum in the late second stage of labour . FINDINGS warm packs were highly acceptable to both women and midwives as a means of relieving pain during the late second stage of labour . Almost the same number of women ( 79.7 % ) and midwives ( 80.4 % ) felt that the warm packs reduced perineal pain during the birth . Both midwives and women were positive about using warm packs in the future . The majority of women ( 85.7 % ) said that they would like to use perineal warm packs again for their next birth and would recommend them to friends ( 86.1 % ) . Likewise , 91 % of midwives were positive about using the warm packs , with 92.6 % considering using them in the future as part of routine care in the second stage of labour . KEY CONCLUSIONS responses to question naires , eliciting experiences of women and midwives involved in the Warm Pack Trial , demonstrated that the practice of applying perineal warm packs in the late second stage of labour was highly acceptable and effective in helping to relieve perineal pain and increase comfort . IMPLICATION S FOR PRACTICE perineal warm packs should be incorporated into second stage pain relief options available to women during childbirth 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 OBJECTIVE To examine the effects of perineal massage during active labor on the frequency of episiotomy and perineal tearing . METHODS A r and omized controlled study was conducted at a center in Sivas , Turkey , between January 1 , 2010 , and May 31 , 2011 . Healthy pregnant women presenting for their first or second delivery at 37 - 42 weeks of pregnancy were enrolled during the first stage of labor . Participants were r and omly assigned ( 1:1 ) to the massage group ( 10-minute perineal massage with glycerol four times during the first stage and once during the second stage of labor ) or control group ( routine care ) . The frequency of episiotomy and perineal tearing were compared between the groups . Participants and investigators were not masked to group assignment . RESULTS Both groups contained 142 participants . Episiotomy was performed among 44 ( 31.0 % ) women in the massage group and 99 ( 69.7 % ) in the control group ( P = 0.001 ) . Lacerations were recorded among 13 ( 4.2 % ) women in the massage group and 6 ( 4.2 % ) in the control group ( P = 0.096 ) . CONCLUSION Application of perineal massage during active labor decreased the frequency of episiotomy procedures . Clinical Trials.gov : NCT02201615 OBJECTIVE To evaluate the influence of intrapartum persistent occiput posterior position of the fetal head on delivery outcome and anal sphincter injury , with reference to the association with epidural analgesia . METHODS We conducted a prospect i ve observational study of 246 women with persistent occiput posterior position in labor during a 2‐year period , compared with 13,543 contemporaneous vaginal deliveries with occiput anterior position . RESULTS The incidence of persistent occiput posterior position was significantly greater among primiparas ( 2.4 % ) than multiparas ( 1.3 % ; P < .001 ; 95 % confidence interval 1.4 , 2.4 ) and was associated with significantly higher incidences of prolonged pregnancy , induction of labor , oxytocin augmentation of labor , epidural use , and prolonged labor . Only 29 % of primiparas and 55 % of multiparas with persistent occiput posterior position achieved spontaneous vaginal delivery , and the malposition was associated with 12 % of all cesarean deliveries performed because of dystocia . Persistent occiput posterior position was also associated with a sevenfold higher incidence of anal sphincter disruption . Despite a high overall incidence of use of epidural analgesia ( 47 % versus 3 % ) , the institutional incidence of persistent occiput posterior position was lower than that reported 25 years ago . CONCLUSION Persistent occiput posterior position contributed disproportionately to cesarean and instrumental delivery , with fewer than half of the occiput posterior labors ending in spontaneous delivery and the position accounting for 12 % of all cesarean deliveries for dystocia . Persistent occiput posterior position leads to a sevenfold increase in the incidence of anal sphincter injury . Use of epidural analgesia was not related to the malposition OBJECTIVE The purpose of this study was to determine if refraining from coached pushing during the second stage of labor affects postpartum urogynecologic measures of pelvic floor structure and function . STUDY DESIGN Nulliparous women at term were r and omized to coached ( n = 67 ) vs uncoached ( n = 61 ) pushing . At 3 months ' postpartum women underwent urodynamic testing , pelvic organ prolapse examination ( POPQ ) , and pelvic floor neuromuscular assessment . RESULTS Urodynamic testing revealed decreased bladder capacity ( 427 mL vs 482 mL , P = .051 ) and decreased first urge to void ( 160 mL vs 202 mL , P = .025 ) in the coached group . Detrusor overactivity increased 2-fold in the coached group ( 16 % vs 8 % ) , although this difference was not statistically significant ( P = .17 ) . Urodynamic stress incontinence was diagnosed in the coached group in 11/67 ( 16 % ) vs 7/61 ( 12 % ) in the uncoached group ( P = .42 ) . CONCLUSION Coached pushing in the second stage of labor significantly affected urodynamic indices , and was associated with a trend towards increased detrusor overactivity OBJECTIVES Our purpose was to evaluate risk factors for severe vaginal-perineal trauma and to ascertain determinants of pelvic floor strength . STUDY DESIGN Secondary analysis of 459 nulliparous women enrolled in a r and omized controlled trial of episiotomy was carried out . In a multivariate analysis we examined the association between ( 1 ) sulcus tears , ( 2 ) third- or fourth-degree tears , and ( 3 ) pelvic floor strength and selected demographic , physiologic , pregnancy-related , and intrapartum factors . RESULTS Unemployment and shorter second stage of labor were significant predictors of sulcus tears . Episiotomy , forceps use , and birth weight were important predictors of third- and fourth-degree tears . Whereas perineal intactness ( use of episiotomy and spontaneous tears ) was not influenced by exercise , a strong exercise profile was associated with fewer third- and fourth-degree tears in the presence of episiotomy . Exercise did not influence the rate of sulcus tears . A total of 35 % of the variability in postpartum pelvic floor strength was explained by antepartum strength ; however , we were only able to identify 5 % of the factors contributing to antepartum pelvic floor strength . CONCLUSIONS Determinants of sulcus tears appear to be present before pregnancy ; third- and fourth-degree tears are related to physician management . Exercise mitigates the potential for severe trauma induced by episiotomy Childbirth can be a fantastic experience for the future mother , but it holds risks for mothers and newborns . Vaginal birth is a result of uterine contractions , minus elastic forces , minus friction force . The objective of this study is to evaluate labor duration , perineal outcomes and safety when applying Gynofit in second stage of labor . Study duration was four months , 120 women were included and r and omized in four groups . Two doses of Gynofit were applicated ( vaginal and perineal dose ) and the duration of second stage of labor was read by electronic chronometer . Results divided by groups were shown , that appyling Gynofit during second stage of labor significantly reduces labor duration by 40 % in primiparous and multiparous women . Gynofit protects pelvic floor and perineum , is safe , is easy to apply , shows no side effects on mother and child 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 OBJECTIVE The objective of this study was to evaluate the protective effects of a new device for reducing perineal tears during vaginal childbirth . STUDY DESIGN A multicenter open r and omized controlled trial ( RCT ) was performed in Helsingborg , Lund and Malmö , Sweden consisting of 1148 women . Women anticipating a vaginal delivery were either r and omized to the intervention group ( n=574 in which the perineal protection device was used , or a control group ( n=574 ) , in which the perineal protection device was not used . The main outcome measurements were incidence of vaginal and perineal tears ( 1st to 4th degree tears ) and adverse effects on the parturient and newborn . RESULTS The incidences of first- and second-degree tears of the vagina ( p=0.018 ) and perineum ( p=0.005 ) were significantly reduced in the intervention group compared with the controls . In the intervention- and control group , 184 women ( 34.9 % ) and 142 ( 26.6 % ) showed no perineal tearing , respectively ( p=0.034 ) . Numbers needed to treat to avoid any perianal tearing was 12 . The incidence of anal sphincter rupture ( ASR ) was the same in both groups ( n=19 ; 3.4 % ) . No negative effects on mother or child from using the device were observed . CONCLUSIONS The perineal protective device significantly reduced the incidence of first- and second-degree tears in the vagina and perineum during vaginal birth and also significantly increased the number of parturients with a fully intact posterior commissure . No significant reduction of ASR and no negative effects of the device were observed |
12,913 | 30,863,156 | Furthermore , the results of the dose – response analysis did not show a significant association between BMD at the lumbar spine , femoral neck , or total hip and the risk of BC .
Conclusion There is no relationship between BMD and the risk of BC . | Purpose The evidence from recent epidemiological studies investigating the relationship between bone mineral density ( BMD ) and the risk of breast cancer ( BC ) remains inconsistent . | Aim To determine the contribution of bone mineral density ( BMD ) to breast cancer risk relative to other established breast cancer risk factors in postmenopausal women with osteoporosis . Methods Data for this analysis comprised those collected from women r and omized to placebo in the MORE and CORE trials ( N = 2,576 ) . Risk factors measured at baseline included age , family history of breast cancer , estradiol level , body mass index , prior hormone therapy , BMD and vertebral fracture status . Cox proportional hazards regression models were used to calculate the hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) . Results Over a total of 13,698 woman-years of follow-up , 65 incident breast cancers occurred . In univariate analyses , older age and family history of breast cancer were the strongest predictors of breast cancer risk , associated with a 2.4- and 2.6-fold increase in breast cancer incidence . A higher estradiol level was associated with a 1.9-fold increase in breast cancer incidence . The association between femoral neck BMD and breast cancer incidence was only significant after adjustment for age ( P = 0.03 ) . The final multivariable model included age , family history , estradiol , BMD , and the BMD-estradiol interaction since the effect of BMD on breast cancer varied by estradiol level ( interaction P-value , 0.04 ) ; in those with a lower estradiol level , a higher BMD was associated with a 2.6-fold increased in breast cancer . Conclusion Overall , BMD is a relatively weak predictor of breast cancer risk in these postmenopausal women with osteoporosis , after taking into consideration age , family history and endogenous estradiol level Study objective : Older women with high bone mineral density ( BMD ) have an increased risk of breast cancer but it is not well known whether this association is associated with the stage of the tumor . The objective of the study is to determine if older women with high BMD are likely to develop a more aggressive form of breast cancer , as defined by mortality . Patients : We prospect ively studied 1504 women who were 75 years of age or older at the entry in the study ( range , 75–90 years ) , between 1992 and 1994 . BMD was measured by dual-photon X-ray absorptiometry at three skeletal sites ( trochanter , Ward 's triangle , femoral neck ) . The women were followed for a mean of 7 years for the occurrence of breast cancer . Cox proportional-hazards models were used to obtain estimates of the relative risk of breast cancer and relative risk of death according to the BMD . Main results : Forty-five incident breast cancer cases were identified . In multivariate analyses of the risk of breast cancer for women in the highest tertile of BMD was greater than for women in the lowest tertile . Indeed , the women with a trochanter BMD in the highest tertile were at 2.3-fold increased risk compared with women in the lowest tertile . The women with highest tertile BMD measured at the Ward 's triangle and at the femoral neck were respectively at 2.2- and 3.3-fold increased risk compared with women at the lowest risk . The 7-year survival rates were markedly less favorable for women in the second and third tertile of the three skeletal sites compared with the lowest tertile . The risk of death was greater for women in the highest tertile of BMD than for women in the lowest tertile at every skeletal site . Conclusion : Elderly women with high BMD have an increased risk of breast cancer , especially advanced cancer , compared with women with low BMD A total of 489 elderly women aged 65 - 75 yr who participated in a 3-yr , r and omized , blinded osteoporosis trial underwent measurements of serum estradiol , bioavailable estradiol , and SHBG . At baseline , bone mineral density ( BMD ) was lower at the femoral sites ( 7 - 19 % , P < 0.05 ) , total body ( 6 - 8 % , P < 0.05 ) , and spine ( 5 - 9 % , P = 0.2 ) in women in the lowest tertile for serum total estradiol [ < 9 pg/ml ( 33 pmol/liter ) ] , serum bioavailable estradiol [ < 2.4 pg/ml ( 8.8 pmol/liter ) ] , or highest tertile for serum SHBG ( > 165 nmol/liter ) , compared with women in the highest tertiles of total estradiol [ > 13.3 pg/ml ( 49 pmol/liter ) ] and bioavailable estradiol [ > 4 pg/ml ( 14 pmol/liter ) ] or lowest tertile for SHBG ( < 113 nmol/liter ) . Bone markers were increased in women in the lowest tertile for serum total estradiol ( not significant ) and bioavailable estradiol ( P < 0.05 ) and highest tertile for SHBG ( P < 0.05 ) . In the longitudinal study , the rate of bone loss in the placebo group was significantly higher in total body ( P < 0.05 ) and spine ( P < 0.05 ) in women in the lowest tertile , compared with the highest tertile of serum bioavailable estradiol . After treatment with conjugated equine estrogens 0.625 mg/d , the increase in BMD was 4 - 6 % higher at the femoral sites ( P < 0.05 ) , total body ( P < 0.05 ) , and spine ( not significant ) , in the lowest tertile , compared with the highest tertile of serum bioavailable estradiol or highest tertile , compared with the lowest tertile of serum SHBG . In summary , small variations in endogenous serum estradiol and high serum SHBG determine differences in BMD and rate of bone loss in elderly women and also affect the response to treatment with estrogen . Women with a serum estradiol level of less than 9 pg/ml ( 33 pmol/liter ) are optimal c and i date s for estrogen therapy for osteoporosis prevention ABSTRACT Objective : To evaluate the relationship between bone mass and risk of breast cancer and to determine the effect of raloxifene therapy on breast cancer incidence in women categorized by bone mass into low bone mass and osteoporosis subgroups . Design : In this post hoc analysis , data were analyzed from the Multiple Outcomes of Raloxifene Evaluation ( MORE ) trial , enrolling postmenopausal women with low bone mass ( N = 7705 ) , and the Continuing Outcomes Relevant to Evista ( CORE ) trial , a follow-up to MORE enrolling 4011 MORE participants . Total follow-up was for up to 8 years . Women with a total hip bone mineral density ( BMD ) T-score < –1 to > –2.5 or T-score ≤ –2.5 ( referent , NHANES III data base ) were classified as having low bone mass or osteoporosis , respectively . Women with a pre-existing vertebral fracture were considered as having osteoporosis irrespective of BMD T-score . Analyses were performed for invasive breast cancers and invasive estrogen-receptor ( ER ) positive breast cancers . Results : Women with low bone mass ( N = 3829 ) had a twofold higher incidence of invasive ER-positive breast cancer than those with osteoporosis ( N = 3836 ) ( HR 2.13 , 95 % CI 1.12–4.03 ) . The incidence of all invasive breast cancers did not differ significantly between the bone mass groups . The incidences of invasive and invasive ER-positive breast cancers were 65–78 % lower in women assigned raloxifene versus placebo in both the low bone mass and osteoporosis groups ( p < 0.05 ) . Conclusions : In this post hoc analysis of postmenopausal women participating in MORE and CORE , bone mass was a predictor of invasive ER-positive breast cancer . Raloxifene treatment reduced the risk of invasive and invasive ER-positive breast cancers in women with low bone mass and those with osteoporosis . Since participants were older postmenopausal women with low bone mass , whether these findings can be generalized to other postmenopausal women is unclear Summary In this prospect i ve study in 2,137 perimenopausal and early postmenopausal women who were followed over a 13.1-year period of time , we observed no association between bone mineral density measured at the beginning of menopause and the subsequent risk of breast cancer . Introduction This study aim ed to investigate the relationship between BMD and the risk of breast cancer ( BC ) in young postmenopausal women . Methods As part of a clinical research program , 2,137 women who were perimenopausal or within their 5 first postmenopausal years were scanned between 1988–1990 and review ed on average 13.1 years after their initial examination . Ninety-eight incident BC cases were recorded throughout the follow-up . Results Women with incident BC significantly differed from those who had never had BC with regard to age at menarche , age of birth of 1st child , familial history of BC and postmenopausal hormone therapy ( PHT ) use . There was no significant difference between the two groups for baseline DXA of the spine . There was a trend for BC cases for having lower femoral neck BMD compared to women without BC . However , women with low BMD were more likely to have taken PHT by the end of the study . In Cox multivariate analyses the relationship between BC risk and femoral neck BMD no longer existed . Conclusions There was no relationship between BMD measured within the first postmenopausal years and the risk of BC , which makes unlikely the possibility of using BMD as a predictor factor for BC in early postmenopausal women OBJECTIVE To test the hypothesis that bone mineral density ( BMD ) is associated with the risk of developing breast cancer in older women . DESIGN Prospect i ve cohort study with mean ( SD ) follow-up of 3.2 ( 1.6 ) years . SETTING Four clinical centers , one each located in the following areas : Baltimore , Md ; Minneapolis , Minn ; Portl and , Ore ; and the Monongahela Valley in Pennsylvania . PARTICIPANTS A total of 6854 nonblack women who were 65 years of age or older and enrolled in the Study of Osteoporotic Fractures . MEASUREMENTS Radius and calcaneus BMD by single photon absorptiometry at baseline ; hip and spine BMD by dual-energy x-ray absorptiometry 2 years later . MAIN OUTCOME MEASURE Breast cancer confirmed by medical record review . RESULTS A total of 97 women developed breast cancer . In the multivariate model , adjusting for age , the degree of obesity , and other important covariates , the risk of breast cancer was about 30 % to 50 % higher per 1 SD increase in BMD ( relative risk , distal radius BMD=1.50 ; 95 % confidence interval , 1.16 - 1.95 ) . The age-adjusted incidence rate of breast cancer per 1000 person-years among women in the lowest quartile of distal radius BMD was 2.46 , compared with 5.99 among women with the highest BMD . Women with BMD above the 25th percentile were at 2.0 to 2.5 times increased risk of breast cancer compared with women below the 25th percentile . Results were consistent across all BMD sites . CONCLUSIONS Bone mineral density predicts the risk of breast cancer in older women . The magnitude of the association is similar to that observed between BMD and all fractures . Our findings suggest a link between 2 of the most common conditions affecting a woman 's health . Identifying a common denominator for these conditions should substantially improve our underst and ing of their etiology and prevention Objective : This case – cohort study was design ed to examine whether total hip bone mineral density ( BMD ) is independently associated with breast cancer over and above its association with other determinants , including levels of total and bioavailable estradiol and testosterone and sex-hormone binding globulin . Methods : Our study population was selected from a cohort of 8203 postmenopausal women who were screened for the Fracture Intervention Trial in 1992 , at which time BMD was assessed , and blood sample s were obtained . A total of 109 women developed breast cancer during four years of follow-up ; 173 other r and omly selected women from the larger cohort were also selected . Cox proportional hazards with robust variance adjustment was used for these analyses . Results : Relative to women in the lower fourth of the BMD distribution , the risk associated with being in the upper fourth was 2.6 ( 95 % confidence interval ( CI ) 1.1–5.8 ) . After adjusting for serum hormone levels , the corresponding relative risk was 2.5 ( 95 % CI 0.9–5.2 ) . With body mass index and number of years since menopause added to the multivariate analysis , the relative risk decreased to 1.4 ( 95 % CI 0.5–4.0 ) . Conclusions : BMD may not influence breast cancer risk independent of its relationship with endogenous hormones and measured covariates |
12,914 | 31,118,808 | Conclusion : The incidence risk of diarrhea associated with PD-1/-PD-L1 inhibitor monotherapy was significantly lower than that of docetaxel monotherapy group .
However it was higher in PD-1/PD-L1 inhibitor combined with chemotherapy group compared with the chemotherapy alone group | Purpose : We design ed the study to illustrate the OR of programmed cell death-1 ( PD-1 ) or lig and 1 ( PD-L1 ) inhibitor-related diarrhea in patients with non-small cell lung cancer . | PURPOSE Programmed death-1 ( PD-1 ) , an inhibitory receptor expressed on activated T cells , may suppress antitumor immunity . This phase I study sought to determine the safety and tolerability of anti-PD-1 blockade in patients with treatment-refractory solid tumors and to preliminarily assess antitumor activity , pharmacodynamics , and immunologic correlates . PATIENTS AND METHODS Thirty-nine patients with advanced metastatic melanoma , colorectal cancer ( CRC ) , castrate-resistant prostate cancer , non-small-cell lung cancer ( NSCLC ) , or renal cell carcinoma ( RCC ) received a single intravenous infusion of anti-PD-1 ( MDX-1106 ) in dose-escalating six-patient cohorts at 0.3 , 1 , 3 , or 10 mg/kg , followed by a 15-patient expansion cohort at 10 mg/kg . Patients with evidence of clinical benefit at 3 months were eligible for repeated therapy . RESULTS Anti-PD-1 was well tolerated : one serious adverse event , inflammatory colitis , was observed in a patient with melanoma who received five doses at 1 mg/kg . One durable complete response ( CRC ) and two partial responses ( PRs ; melanoma , RCC ) were seen . Two additional patients ( melanoma , NSCLC ) had significant lesional tumor regressions not meeting PR criteria . The serum half-life of anti-PD-1 was 12 to 20 days . However , pharmacodynamics indicated a sustained mean occupancy of > 70 % of PD-1 molecules on circulating T cells > or = 2 months following infusion , regardless of dose . In nine patients examined , tumor cell surface B7-H1 expression appeared to correlate with the likelihood of response to treatment . CONCLUSION Blocking the PD-1 immune checkpoint with intermittent antibody dosing is well tolerated and associated with evidence of antitumor activity . Exploration of alternative dosing regimens and combinatorial therapies with vaccines , targeted therapies , and /or other checkpoint inhibitors is warranted Therapies that target the programmed death-1 ( PD-1 ) receptor have shown unprecedented rates of durable clinical responses in patients with various cancer types . One mechanism by which cancer tissues limit the host immune response is via upregulation of PD-1 lig and ( PD-L1 ) and its ligation to PD-1 on antigen-specific CD8 + T cells ( termed adaptive immune resistance ) . Here we show that pre-existing CD8 + T cells distinctly located at the invasive tumour margin are associated with expression of the PD-1/PD-L1 immune inhibitory axis and may predict response to therapy . We analysed sample s from 46 patients with metastatic melanoma obtained before and during anti-PD-1 therapy ( pembrolizumab ) using quantitative immunohistochemistry , quantitative multiplex immunofluorescence , and next-generation sequencing for T-cell antigen receptors ( TCRs ) . In serially sample d tumours , patients responding to treatment showed proliferation of intratumoral CD8 + T cells that directly correlated with radiographic reduction in tumour size . Pre-treatment sample s obtained from responding patients showed higher numbers of CD8- , PD-1- and PD-L1-expressing cells at the invasive tumour margin and inside tumours , with close proximity between PD-1 and PD-L1 , and a more clonal TCR repertoire . Using multivariate analysis , we established a predictive model based on CD8 expression at the invasive margin and vali date d the model in an independent cohort of 15 patients . Our findings indicate that tumour regression after therapeutic PD-1 blockade requires pre-existing CD8 + T cells that are negatively regulated by PD-1/PD-L1-mediated adaptive immune resistance BACKGROUND Results from phase 2 and 3 trials in patients with advanced melanoma have shown significant improvements in the proportion of patients achieving an objective response and prolonged progression-free survival with the combination of nivolumab ( an anti-PD-1 antibody ) plus ipilimumab ( an anti-CTLA-4 antibody ) compared with ipilimumab alone . We report 2-year overall survival data from a r and omised controlled trial assessing this treatment in previously untreated advanced melanoma . METHODS In this multicentre , double-blind , r and omised , controlled , phase 2 trial ( CheckMate 069 ) we recruited patients from 19 specialist cancer centres in two countries ( France and the USA ) . Eligible patients were aged 18 years or older with previously untreated , unresectable stage III or IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 . Patients were r and omly assigned 2:1 to receive an intravenous infusion of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg or ipilimumab 3 mg/kg plus placebo , every 3 weeks for four doses . Subsequently , patients assigned to nivolumab plus ipilimumab received nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity , whereas patients allocated to ipilimumab alone received placebo every 2 weeks during this phase . R and omisation was done via an interactive voice response system with a permuted block schedule ( block size of six ) and stratification by BRAF mutation status . The study funder , patients , investigators , and study site staff were masked to treatment assignment . The primary endpoint , which has been reported previously , was the proportion of patients with BRAFV600 wild-type melanoma achieving an investigator-assessed objective response . Overall survival was an exploratory endpoint and is reported in this Article . Efficacy analyses were done on the intention-to-treat population , whereas safety was assessed in all treated patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT01927419 , and is ongoing but no longer enrolling patients . FINDINGS Between Sept 16 , 2013 , and Feb 6 , 2014 , we screened 179 patients and enrolled 142 , r and omly assigning 95 patients to nivolumab plus ipilimumab and 47 to ipilimumab alone . In each treatment group , one patient no longer met the study criteria following r and omisation and thus did not receive study drug . At a median follow-up of 24·5 months ( IQR 9·1 - 25·7 ) , 2-year overall survival was 63·8 % ( 95 % CI 53·3 - 72·6 ) for those assigned to nivolumab plus ipilimumab and 53·6 % ( 95 % CI 38·1 - 66·8 ) for those assigned to ipilimumab alone ; median overall survival had not been reached in either group ( hazard ratio 0·74 , 95 % CI 0·43 - 1·26 ; p=0·26 ) . Treatment-related grade 3 - 4 adverse events were reported in 51 ( 54 % ) of 94 patients who received nivolumab plus ipilimumab compared with nine ( 20 % ) of 46 patients who received ipilimumab alone . The most common treatment-related grade 3 - 4 adverse events were colitis ( 12 [ 13 % ] of 94 patients ) and increased alanine aminotransferase ( ten [ 11 % ] ) in the combination group and diarrhoea ( five [ 11 % ] of 46 patients ) and hypophysitis ( two [ 4 % ] ) in the ipilimumab alone group . Serious grade 3 - 4 treatment-related adverse events were reported in 34 ( 36 % ) of 94 patients who received nivolumab plus ipilimumab ( including colitis in ten [ 11 % ] of 94 patients , and diarrhoea in five [ 5 % ] ) compared with four ( 9 % ) of 46 patients who received ipilimumab alone ( including diarrhoea in two [ 4 % ] of 46 patients , colitis in one [ 2 % ] , and hypophysitis in one [ 2 % ] ) . No new types of treatment-related adverse events or treatment-related deaths occurred in this up date d analysis . INTERPRETATION Although follow-up of the patients in this study is ongoing , the results of this analysis suggest that the combination of first-line nivolumab plus ipilimumab might lead to improved outcomes compared with first-line ipilimumab alone in patients with advanced melanoma . The results suggest encouraging survival outcomes with immunotherapy in this population of patients . FUNDING Bristol-Myers Squibb BACKGROUND Limited evidence exists to show that adding a third agent to platinum-doublet chemotherapy improves efficacy in the first-line advanced non-small-cell lung cancer ( NSCLC ) setting . The anti-PD-1 antibody pembrolizumab has shown efficacy as monotherapy in patients with advanced NSCLC and has a non-overlapping toxicity profile with chemotherapy . We assessed whether the addition of pembrolizumab to platinum-doublet chemotherapy improves efficacy in patients with advanced non-squamous NSCLC . METHODS In this r and omised , open-label , phase 2 cohort of a multicohort study ( KEYNOTE-021 ) , patients were enrolled at 26 medical centres in the USA and Taiwan . Patients with chemotherapy-naive , stage IIIB or IV , non-squamous NSCLC without targetable EGFR or ALK genetic aberrations were r and omly assigned ( 1:1 ) in blocks of four stratified by PD-L1 tumour proportion score ( < 1 % vs ≥1 % ) using an interactive voice-response system to 4 cycles of pembrolizumab 200 mg plus carboplatin area under curve 5 mg/mL per min and pemetrexed 500 mg/m2 every 3 weeks followed by pembrolizumab for 24 months and indefinite pemetrexed maintenance therapy or to 4 cycles of carboplatin and pemetrexed alone followed by indefinite pemetrexed maintenance therapy . The primary endpoint was the proportion of patients who achieved an objective response , defined as the percentage of patients with radiologically confirmed complete or partial response according to Response Evaluation Criteria in Solid Tumors version 1.1 assessed by masked , independent central review , in the intention-to-treat population , defined as all patients who were allocated to study treatment . Significance threshold was p<0·025 ( one sided ) . Safety was assessed in the as-treated population , defined as all patients who received at least one dose of the assigned study treatment . This trial , which is closed for enrolment but continuing for follow-up , is registered with Clinical Trials.gov , number NCT02039674 . FINDINGS Between Nov 25 , 2014 , and Jan 25 , 2016 , 123 patients were enrolled ; 60 were r and omly assigned to the pembrolizumab plus chemotherapy group and 63 to the chemotherapy alone group . 33 ( 55 % ; 95 % CI 42 - 68 ) of 60 patients in the pembrolizumab plus chemotherapy group achieved an objective response compared with 18 ( 29 % ; 18 - 41 ) of 63 patients in the chemotherapy alone group ( estimated treatment difference 26 % [ 95 % CI 9 - 42 % ] ; p=0·0016 ) . The incidence of grade 3 or worse treatment-related adverse events was similar between groups ( 23 [ 39 % ] of 59 patients in the pembrolizumab plus chemotherapy group and 16 [ 26 % ] of 62 in the chemotherapy alone group ) . The most common grade 3 or worse treatment-related adverse events in the pembrolizumab plus chemotherapy group were anaemia ( seven [ 12 % ] of 59 ) and decreased neutrophil count ( three [ 5 % ] ) ; an additional six events each occurred in two ( 3 % ) for acute kidney injury , decreased lymphocyte count , fatigue , neutropenia , and sepsis , and thrombocytopenia . In the chemotherapy alone group , the most common grade 3 or worse events were anaemia ( nine [ 15 % ] of 62 ) and decreased neutrophil count , pancytopenia , and thrombocytopenia ( two [ 3 % ] each ) . One ( 2 % ) of 59 patients in the pembrolizumab plus chemotherapy group experienced treatment-related death because of sepsis compared with two ( 3 % ) of 62 patients in the chemotherapy group : one because of sepsis and one because of pancytopenia . INTERPRETATION Combination of pembrolizumab , carboplatin , and pemetrexed could be an effective and tolerable first-line treatment option for patients with advanced non-squamous NSCLC . This finding is being further explored in an ongoing international , r and omised , double-blind , phase 3 study . FUNDING Merck & BACKGROUND Atezolizumab is a humanised antiprogrammed death-lig and 1 ( PD-L1 ) monoclonal antibody that inhibits PD-L1 and programmed death-1 ( PD-1 ) and PD-L1 and B7 - 1 interactions , reinvigorating anticancer immunity . We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer . METHODS We did a r and omised , open-label , phase 3 trial ( OAK ) in 194 academic or community oncology centres in 31 countries . We enrolled patients who had squamous or non-squamous non-small-cell lung cancer , were 18 years or older , had measurable disease per Response Evaluation Criteria in Solid Tumors , and had an Eastern Cooperative Oncology Group performance status of 0 or 1 . Patients had received one to two previous cytotoxic chemotherapy regimens ( one or more platinum based combination therapies ) for stage IIIB or IV non-small-cell lung cancer . Patients with a history of autoimmune disease and those who had received previous treatments with docetaxel , CD137 agonists , anti-CTLA4 , or therapies targeting the PD-L1 and PD-1 pathway were excluded . Patients were r and omly assigned ( 1:1 ) to intravenously receive either atezolizumab 1200 mg or docetaxel 75 mg/m2 every 3 weeks by permuted block r and omisation ( block size of eight ) via an interactive voice or web response system . Co primary endpoints were overall survival in the intention-to-treat ( ITT ) and PD-L1-expression population TC1/2/3 or IC1/2/3 ( ≥1 % PD-L1 on tumour cells or tumour-infiltrating immune cells ) . The primary efficacy analysis was done in the first 850 of 1225 enrolled patients . This study is registered with Clinical Trials.gov , number NCT02008227 . FINDINGS Between March 11 , 2014 , and April 29 , 2015 , 1225 patients were recruited . In the primary population , 425 patients were r and omly assigned to receive atezolizumab and 425 patients were assigned to receive docetaxel . Overall survival was significantly longer with atezolizumab in the ITT and PD-L1-expression population s. In the ITT population , overall survival was improved with atezolizumab compared with docetaxel ( median overall survival was 13·8 months [ 95 % CI 11·8 - 15·7 ] vs 9·6 months [ 8·6 - 11·2 ] ; hazard ratio [ HR ] 0·73 [ 95 % CI 0·62 - 0·87 ] , p=0·0003 ) . Overall survival in the TC1/2/3 or IC1/2/3 population was improved with atezolizumab ( n=241 ) compared with docetaxel ( n=222 ; median overall survival was 15·7 months [ 95 % CI 12·6 - 18·0 ] with atezolizumab vs 10·3 months [ 8·8 - 12·0 ] with docetaxel ; HR 0·74 [ 95 % CI 0·58 - 0·93 ] ; p=0·0102 ) . Patients in the PD-L1 low or undetectable subgroup ( TC0 and IC0 ) also had improved survival with atezolizumab ( median overall survival 12·6 months vs 8·9 months ; HR 0·75 [ 95 % CI 0·59 - 0·96 ] ) . Overall survival improvement was similar in patients with squamous ( HR 0·73 [ 95 % CI 0·54 - 0·98 ] ; n=112 in the atezolizumab group and n=110 in the docetaxel group ) or non-squamous ( 0·73 [ 0·60 - 0·89 ] ; n=313 and n=315 ) histology . Fewer patients had treatment-related grade 3 or 4 adverse events with atezolizumab ( 90 [ 15 % ] of 609 patients ) versus docetaxel ( 247 [ 43 % ] of 578 patients ) . One treatment-related death from a respiratory tract infection was reported in the docetaxel group . INTERPRETATION To our knowledge , OAK is the first r and omised phase 3 study to report results of a PD-L1-targeted therapy , with atezolizumab treatment result ing in a clinical ly relevant improvement of overall survival versus docetaxel in previously treated non-small-cell lung cancer , regardless of PD-L1 expression or histology , with a favourable safety profile . FUNDING F. Hoffmann-La Roche Ltd , Genentech , BACKGROUND Nivolumab plus ipilimumab showed promising efficacy for the treatment of non – small‐cell lung cancer ( NSCLC ) in a phase 1 trial , and tumor mutational burden has emerged as a potential biomarker of benefit . In this part of an open‐label , multipart , phase 3 trial , we examined progression‐free survival with nivolumab plus ipilimumab versus chemotherapy among patients with a high tumor mutational burden ( ≥10 mutations per megabase ) . METHODS We enrolled patients with stage IV or recurrent NSCLC that was not previously treated with chemotherapy . Those with a level of tumor programmed death lig and 1 ( PD‐L1 ) expression of at least 1 % were r and omly assigned , in a 1:1:1 ratio , to receive nivolumab plus ipilimumab , nivolumab monotherapy , or chemotherapy ; those with a tumor PD‐L1 expression level of less than 1 % were r and omly assigned , in a 1:1:1 ratio , to receive nivolumab plus ipilimumab , nivolumab plus chemotherapy , or chemotherapy . Tumor mutational burden was determined by the FoundationOne CDx assay . RESULTS Progression‐free survival among patients with a high tumor mutational burden was significantly longer with nivolumab plus ipilimumab than with chemotherapy . The 1‐year progression‐free survival rate was 42.6 % with nivolumab plus ipilimumab versus 13.2 % with chemotherapy , and the median progression‐free survival was 7.2 months ( 95 % confidence interval [ CI ] , 5.5 to 13.2 ) versus 5.5 months ( 95 % CI , 4.4 to 5.8 ) ( hazard ratio for disease progression or death , 0.58 ; 97.5 % CI , 0.41 to 0.81 ; P<0.001 ) . The objective response rate was 45.3 % with nivolumab plus ipilimumab and 26.9 % with chemotherapy . The benefit of nivolumab plus ipilimumab over chemotherapy was broadly consistent within subgroups , including patients with a PD‐L1 expression level of at least 1 % and those with a level of less than 1 % . The rate of grade 3 or 4 treatment‐related adverse events was 31.2 % with nivolumab plus ipilimumab and 36.1 % with chemotherapy . CONCLUSIONS Progression‐free survival was significantly longer with first‐line nivolumab plus ipilimumab than with chemotherapy among patients with NSCLC and a high tumor mutational burden , irrespective of PD‐L1 expression level . The results vali date the benefit of nivolumab plus ipilimumab in NSCLC and the role of tumor mutational burden as a biomarker for patient selection . ( Funded by Bristol‐Myers Squibb and Ono Pharmaceutical ; CheckMate 227 Clinical Trials.gov number , NCT02477826 . BACKGROUND Nivolumab , a fully human IgG4 programmed death 1 ( PD-1 ) immune-checkpoint-inhibitor antibody , disrupts PD-1-mediated signaling and may restore antitumor immunity . METHODS In this r and omized , open-label , international phase 3 study , we assigned patients with nonsquamous non-small-cell lung cancer ( NSCLC ) that had progressed during or after platinum-based doublet chemotherapy to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of 75 mg per square meter of body-surface area every 3 weeks . The primary end point was overall survival . RESULTS Overall survival was longer with nivolumab than with docetaxel . The median overall survival was 12.2 months ( 95 % confidence interval [ CI ] , 9.7 to 15.0 ) among 292 patients in the nivolumab group and 9.4 months ( 95 % CI , 8.1 to 10.7 ) among 290 patients in the docetaxel group ( hazard ratio for death , 0.73 ; 96 % CI , 0.59 to 0.89 ; P=0.002 ) . At 1 year , the overall survival rate was 51 % ( 95 % CI , 45 to 56 ) with nivolumab versus 39 % ( 95 % CI , 33 to 45 ) with docetaxel . With additional follow-up , the overall survival rate at 18 months was 39 % ( 95 % CI , 34 to 45 ) with nivolumab versus 23 % ( 95 % CI , 19 to 28 ) with docetaxel . The response rate was 19 % with nivolumab versus 12 % with docetaxel ( P=0.02 ) . Although progression-free survival did not favor nivolumab over docetaxel ( median , 2.3 months and 4.2 months , respectively ) , the rate of progression-free survival at 1 year was higher with nivolumab than with docetaxel ( 19 % and 8 % , respectively ) . Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression ( ≥1 % , ≥5 % , and ≥10 % ) of the PD-1 lig and . Treatment-related adverse events of grade 3 or 4 were reported in 10 % of the patients in the nivolumab group , as compared with 54 % of those in the docetaxel group . CONCLUSIONS Among patients with advanced nonsquamous NSCLC that had progressed during or after platinum-based chemotherapy , overall survival was longer with nivolumab than with docetaxel . ( Funded by Bristol-Myers Squibb ; CheckMate 057 Clinical Trials.gov number , NCT01673867 . ) BACKGROUND Patients with advanced squamous-cell non-small-cell lung cancer ( NSCLC ) who have disease progression during or after first-line chemotherapy have limited treatment options . This r and omized , open-label , international , phase 3 study evaluated the efficacy and safety of nivolumab , a fully human IgG4 programmed death 1 ( PD-1 ) immune-checkpoint-inhibitor antibody , as compared with docetaxel in this patient population . METHODS We r and omly assigned 272 patients to receive nivolumab , at a dose of 3 mg per kilogram of body weight every 2 weeks , or docetaxel , at a dose of 75 mg per square meter of body-surface area every 3 weeks . The primary end point was overall survival . RESULTS The median overall survival was 9.2 months ( 95 % confidence interval [ CI ] , 7.3 to 13.3 ) with nivolumab versus 6.0 months ( 95 % CI , 5.1 to 7.3 ) with docetaxel . The risk of death was 41 % lower with nivolumab than with docetaxel ( hazard ratio , 0.59 ; 95 % CI , 0.44 to 0.79 ; P<0.001 ) . At 1 year , the overall survival rate was 42 % ( 95 % CI , 34 to 50 ) with nivolumab versus 24 % ( 95 % CI , 17 to 31 ) with docetaxel . The response rate was 20 % with nivolumab versus 9 % with docetaxel ( P=0.008 ) . The median progression-free survival was 3.5 months with nivolumab versus 2.8 months with docetaxel ( hazard ratio for death or disease progression , 0.62 ; 95 % CI , 0.47 to 0.81 ; P<0.001 ) . The expression of the PD-1 lig and ( PD-L1 ) was neither prognostic nor predictive of benefit . Treatment-related adverse events of grade 3 or 4 were reported in 7 % of the patients in the nivolumab group as compared with 55 % of those in the docetaxel group . CONCLUSIONS Among patients with advanced , previously treated squamous-cell NSCLC , overall survival , response rate , and progression-free survival were significantly better with nivolumab than with docetaxel , regardless of PD-L1 expression level . ( Funded by Bristol-Myers Squibb ; CheckMate 017 Clinical Trials.gov number , NCT01642004 . ) BACKGROUND Outcomes are poor for patients with previously treated , advanced or metastatic non-small-cell lung cancer ( NSCLC ) . The anti-programmed death lig and 1 ( PD-L1 ) antibody atezolizumab is clinical ly active against cancer , including NSCLC , especially cancers expressing PD-L1 on tumour cells , tumour-infiltrating immune cells , or both . We assessed efficacy and safety of atezolizumab versus docetaxel in previously treated NSCLC , analysed by PD-L1 expression levels on tumour cells and tumour-infiltrating immune cells and in the intention-to-treat population . METHODS In this open-label , phase 2 r and omised controlled trial , patients with NSCLC who progressed on post-platinum chemotherapy were recruited in 61 academic medical centres and community oncology practice s across 13 countries in Europe and North America . Key inclusion criteria were Eastern Cooperative Oncology Group performance status 0 or 1 , measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 ( RECIST v1.1 ) , and adequate haematological and end-organ function . Patients were stratified by PD-L1 tumour-infiltrating immune cell status , histology , and previous lines of therapy , and r and omly assigned ( 1:1 ) by permuted block r and omisation ( with a block size of four ) using an interactive voice or web system to receive intravenous atezolizumab 1200 mg or docetaxel 75 mg/m(2 ) once every 3 weeks . Baseline PD-L1 expression was scored by immunohistochemistry in tumour cells ( as percentage of PD-L1-expressing tumour cells TC3≥50 % , TC2≥5 % and < 50 % , TC1≥1 % and < 5 % , and TC0<1 % ) and tumour-infiltrating immune cells ( as percentage of tumour area : IC3≥10 % , IC2≥5 % and < 10 % , IC1≥1 % and < 5 % , and IC0<1 % ) . The primary endpoint was overall survival in the intention-to-treat population and PD-L1 subgroups at 173 deaths . Biomarkers were assessed in an exploratory analysis . We assessed safety in all patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT01903993 . FINDINGS Patients were enrolled between Aug 5 , 2013 , and March 31 , 2014 . 144 patients were r and omly allocated to the atezolizumab group , and 143 to the docetaxel group . 142 patients received at least one dose of atezolizumab and 135 received docetaxel . Overall survival in the intention-to-treat population was 12·6 months ( 95 % CI 9·7 - 16·4 ) for atezolizumab versus 9·7 months ( 8·6 - 12·0 ) for docetaxel ( hazard ratio [ HR ] 0·73 [ 95 % CI 0·53 - 0·99 ] ; p=0·04 ) . Increasing improvement in overall survival was associated with increasing PD-L1 expression ( TC3 or IC3 HR 0·49 [ 0·22 - 1·07 ; p=0·068 ] , TC2/3 or IC2/3 HR 0·54 [ 0·33 - 0·89 ; p=0·014 ] , TC1/2/3 or IC1/2/3 HR 0·59 [ 0·40 - 0·85 ; p=0·005 ] , TC0 and IC0 HR 1·04 [ 0·62 - 1·75 ; p=0·871 ] ) . In our exploratory analysis , patients with pre-existing immunity , defined by high T-effector-interferon-γ-associated gene expression , had improved overall survival with atezolizumab . 11 ( 8 % ) patients in the atezolizumab group discontinued because of adverse events versus 30 ( 22 % ) patients in the docetaxel group . 16 ( 11 % ) patients in the atezolizumab group versus 52 ( 39 % ) patients in the docetaxel group had treatment-related grade 3 - 4 adverse events , and one ( < 1 % ) patient in the atezolizumab group versus three ( 2 % ) patients in the docetaxel group died from a treatment-related adverse event . INTERPRETATION Atezolizumab significantly improved survival compared with docetaxel in patients with previously treated NSCLC . Improvement correlated with PD-L1 immunohistochemistry expression on tumour cells and tumour-infiltrating immune cells , suggesting that PD-L1 expression is predictive for atezolizumab benefit . Atezolizumab was well tolerated , with a safety profile distinct from chemotherapy . FUNDING F Hoffmann-La Roche/Genentech PURPOSE To confirm the promising phase II results of docetaxel monotherapy , this phase III trial was conducted of chemotherapy for patients with advanced non-small-cell lung cancer ( NSCLC ) who had previously failed platinum-containing chemotherapy . PATIENTS AND METHODS A total of 373 patients were r and omized to receive either docetaxel 100 mg/m(2 ) ( D100 ) or 75 mg/m(2 ) ( D75 ) versus a control regimen of vinorelbine or ifosfamide ( V/I ) . The three treatment groups were well-balanced for key patient characteristics . RESULTS Overall response rates were 10.8 % with D100 and 6.7 % with D75 , each significantly higher than the 0.8 % response with V/I ( P = .001 and P = .036 , respectively ) . Patients who received docetaxel had a longer time to progression ( P = .046 , by log-rank test ) and a greater progression-free survival at 26 weeks ( P = .005 , by chi(2 ) test ) . Although overall survival was not significantly different between the three groups , the 1-year survival was significantly greater with D75 than with the control treatment ( 32 % v 19 % ; P = .025 , by chi(2 ) test ) . Prior exposure to paclitaxel did not decrease the likelihood of response to docetaxel , nor did it impact survival . There was a trend toward greater efficacy in patients whose disease was platinum-resistant rather than platinum-refractory and in patients with performance status of 0 or 1 versus 2 . Toxicity was greatest with D100 , but the D75 arm was well-tolerated . CONCLUSION This first r and omized trial in this setting demonstrates that D75 every 3 weeks can offer clinical ly meaningful benefit to patients with advanced NSCLC whose disease has relapsed or progressed after platinum-based chemotherapy Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more PURPOSE To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non-small-cell lung cancer who had previously been treated with platinum-based chemotherapy . Secondary end points included assessment of response ( docetaxel arm only ) , toxicity , and quality of life . PATIENTS AND METHODS Patients with performance statuses of 0 to 2 and stage IIIB/IV non-small-cell lung cancer with either measurable or evaluable lesions were eligible for entry onto the study if they had undergone one or more platinum-based chemotherapy regimens and if they had adequate hematology and biochemistry parameters . They were excluded if they had symptomatic brain metastases or if they had previously been treated with paclitaxel . Patients were stratified by performance status and best response to cisplatin chemotherapy and were then r and omized to treatment with docetaxel 100 mg/m(2 ) ( 49 patients ) or 75 mg/m(2 ) ( 55 patients ) or best supportive care . Patients in both arms were assessed every 3 weeks . RESULTS One hundred four patients ( 103 of whom were eligible for entry onto the study ) were well balanced for prognostic factors . Of 84 patients with measurable lesions , six ( 7 . 1 % ) achieved partial responses ( three patients at each dose level ) . Time to progression was longer for docetaxel patients than for best supportive care patients ( 10.6 v 6.7 weeks , respectively ; P < .001 ) , as was median survival ( 7.0 v 4.6 months ; log-rank test , P = .047 ) . The difference was more significant for docetaxel 75 mg/m(2 ) patients , compared with corresponding best supportive care patients ( 7.5 v 4.6 months ; log-rank test , P = .010 ; 1-year survival , 37 % v 11 % ; chi(2 ) test , P = .003 ) . Febrile neutropenia occurred in 11 patients treated with docetaxel 100 mg/m(2 ) , three of whom died , and in one patient treated with docetaxel 75 mg/m(2 ) . Grade 3 or 4 nonhematologic toxicity , with the exception of diarrhea , occurred at a similar rate in both the docetaxel and best supportive care groups . CONCLUSION Treatment with docetaxel is associated with significant prolongation of survival , and at a dose of 75 mg/m(2 ) , the benefits of docetaxel therapy outweigh the risks BACKGROUND Despite recent advances in the treatment of advanced non-small-cell lung cancer , there remains a need for effective treatments for progressive disease . We assessed the efficacy of pembrolizumab for patients with previously treated , PD-L1-positive , advanced non-small-cell lung cancer . METHODS We did this r and omised , open-label , phase 2/3 study at 202 academic medical centres in 24 countries . Patients with previously treated non-small-cell lung cancer with PD-L1 expression on at least 1 % of tumour cells were r and omly assigned ( 1:1:1 ) in blocks of six per stratum with an interactive voice-response system to receive pembrolizumab 2 mg/kg , pembrolizumab 10 mg/kg , or docetaxel 75 mg/m(2 ) every 3 weeks . The primary endpoints were overall survival and progression-free survival both in the total population and in patients with PD-L1 expression on at least 50 % of tumour cells . We used a threshold for significance of p<0.00825 ( one-sided ) for the analysis of overall survival and a threshold of p<0.001 for progression-free survival . This trial is registered at Clinical Trials.gov , number NCT01905657 . FINDINGS Between Aug 28 , 2013 , and Feb 27 , 2015 , we enrolled 1034 patients : 345 allocated to pembrolizumab 2 mg/kg , 346 allocated to pembrolizumab 10 mg/kg , and 343 allocated to docetaxel . By Sept 30 , 2015 , 521 patients had died . In the total population , median overall survival was 10.4 months with pembrolizumab 2 mg/kg , 12.7 months with pembrolizumab 10 mg/kg , and 8.5 months with docetaxel . Overall survival was significantly longer for pembrolizumab 2 mg/kg versus docetaxel ( hazard ratio [ HR ] 0.71 , 95 % CI 0.58 - 0.88 ; p=0.0008 ) and for pembrolizumab 10 mg/kg versus docetaxel ( 0.61 , 0.49 - 0.75 ; p<0.0001 ) . Median progression-free survival was 3.9 months with pembrolizumab 2 mg/kg , 4.0 months with pembrolizumab 10 mg/kg , and 4.0 months with docetaxel , with no significant difference for pembrolizumab 2 mg/kg versus docetaxel ( 0.88 , 0.74 - 1.05 ; p=0.07 ) or for pembrolizumab 10 mg/kg versus docetaxel ( HR 0.79 , 95 % CI 0.66 - 0.94 ; p=0.004 ) . Among patients with at least 50 % of tumour cells expressing PD-L1 , overall survival was significantly longer with pembrolizumab 2 mg/kg than with docetaxel ( median 14.9 months vs 8.2 months ; HR 0.54 , 95 % CI 0.38 - 0.77 ; p=0.0002 ) and with pembrolizumab 10 mg/kg than with docetaxel ( 17.3 months vs 8.2 months ; 0.50 , 0.36 - 0.70 ; p<0.0001 ) . Likewise , for this patient population , progression-free survival was significantly longer with pembrolizumab 2 mg/kg than with docetaxel ( median 5.0 months vs 4.1 months ; HR 0.59 , 95 % CI 0.44 - 0.78 ; p=0.0001 ) and with pembrolizumab 10 mg/kg than with docetaxel ( 5.2 months vs 4.1 months ; 0.59 , 0.45 - 0.78 ; p<0.0001 ) . Grade 3 - 5 treatment-related adverse events were less common with pembrolizumab than with docetaxel ( 43 [ 13 % ] of 339 patients given 2 mg/kg , 55 [ 16 % ] of 343 given 10 mg/kg , and 109 [ 35 % ] of 309 given docetaxel ) . INTERPRETATION Pembrolizumab prolongs overall survival and has a favourable benefit-to-risk profile in patients with previously treated , PD-L1-positive , advanced non-small-cell lung cancer . These data establish pembrolizumab as a new treatment option for this population and vali date the use of PD-L1 selection . FUNDING Merck & PURPOSE To compare the efficacy and toxicity of pemetrexed versus docetaxel in patients with advanced non-small-cell lung cancer ( NSCLC ) previously treated with chemotherapy . PATIENTS AND METHODS Eligible patients had a performance status 0 to 2 , previous treatment with one prior chemotherapy regimen for advanced NSCLC , and adequate organ function . Patients received pemetrexed 500 mg/m(2 ) intravenously ( i.v . ) day 1 with vitamin B(12 ) , folic acid , and dexamethasone or docetaxel 75 mg/m(2 ) i.v . day 1 with dexamethasone every 21 days . The primary end point was overall survival . RESULTS Five hundred seventy-one patients were r and omly assigned . Overall response rates were 9.1 % and 8.8 % ( analysis of variance P = .105 ) for pemetrexed and docetaxel , respectively . Median progression-free survival was 2.9 months for each arm , and median survival time was 8.3 versus 7.9 months ( P = not significant ) for pemetrexed and docetaxel , respectively . The 1-year survival rate for each arm was 29.7 % . Patients receiving docetaxel were more likely to have grade 3 or 4 neutropenia ( 40.2 % v 5.3 % ; P < .001 ) , febrile neutropenia ( 12.7 % v 1.9 % ; P < .001 ) , neutropenia with infections ( 3.3 % v 0.0 % ; P = .004 ) , hospitalizations for neutropenic fever ( 13.4 % v 1.5 % ; P < .001 ) , hospitalizations due to other drug related adverse events ( 10.5 % v 6.4 % ; P = .092 ) , use of granulocyte colony-stimulating factor support ( 19.2 % v 2.6 % , P < .001 ) and all grade alopecia ( 37.7 % v 6.4 % ; P < .001 ) compared with patients receiving pemetrexed . CONCLUSION Treatment with pemetrexed result ed in clinical ly equivalent efficacy outcomes , but with significantly fewer side effects compared with docetaxel in the second-line treatment of patients with advanced NSCLC and should be considered a st and ard treatment option for second-line NSCLC when available Background No systemic therapies have been approved for the treatment of advanced cutaneous squamous‐cell carcinoma . This cancer may be responsive to immune therapy , because the mutation burden of the tumor is high and the disease risk is strongly associated with immunosuppression . In the dose‐escalation portion of the phase 1 study of cemiplimab , a deep and durable response was observed in a patient with metastatic cutaneous squamous‐cell carcinoma . Methods We report the results of the phase 1 study of cemiplimab for expansion cohorts of patients with locally advanced or metastatic cutaneous squamous‐cell carcinoma , as well as the results of the pivotal phase 2 study for a cohort of patients with metastatic disease ( metastatic‐disease cohort ) . In both studies , the patients received an intravenous dose of cemiplimab ( 3 mg per kilogram of body weight ) every 2 weeks and were assessed for a response every 8 weeks . In the phase 2 study , the primary end point was the response rate , as assessed by independent central review . Results In the expansion cohorts of the phase 1 study , a response to cemiplimab was observed in 13 of 26 patients ( 50 % ; 95 % confidence interval [ CI ] , 30 to 70 ) . In the metastatic‐disease cohort of the phase 2 study , a response was observed in 28 of 59 patients ( 47 % ; 95 % CI , 34 to 61 ) . The median follow‐up was 7.9 months in the metastatic‐disease cohort of the phase 2 study . Among the 28 patients who had a response , the duration of response exceeded 6 months in 57 % , and 82 % continued to have a response and to receive cemiplimab at the time of data cutoff . Adverse events that occurred in at least 15 % of the patients in the metastatic‐disease cohort of the phase 2 study were diarrhea , fatigue , nausea , constipation , and rash ; 7 % of the patients discontinued treatment because of an adverse event . Conclusions Among patients with advanced cutaneous squamous‐cell carcinoma , cemiplimab induced a response in approximately half the patients and was associated with adverse events that usually occur with immune checkpoint inhibitors . ( Funded by Regeneron Pharmaceuticals and Sanofi ; Clinical Trials.gov numbers , NCT02383212 and NCT02760498 . BACKGROUND Antibodies targeting the immune checkpoint molecules PD-1 or PD-L1 have demonstrated clinical efficacy in patients with metastatic non-small-cell lung cancer ( NSCLC ) . In this trial we investigated the efficacy and safety of avelumab , an anti-PD-L1 antibody , in patients with NSCLC who had already received platinum-based therapy . METHODS JAVELIN Lung 200 was a multicentre , open-label , r and omised , phase 3 trial at 173 hospitals and cancer treatment centres in 31 countries . Eligible patients were aged 18 years or older and had stage IIIB or IV or recurrent NSCLC and disease progression after treatment with a platinum-containing doublet , an Eastern Cooperative Oncology Group performance status score of 0 or 1 , an estimated life expectancy of more than 12 weeks , and adequate haematological , renal , and hepatic function . Participants were r and omly assigned ( 1:1 ) , via an interactive voice-response system with a stratified permuted block method with variable block length , to receive either avelumab 10 mg/kg every 2 weeks or docetaxel 75 mg/m2 every 3 weeks . R and omisation was stratified by PD-L1 expression ( ≥1 % vs < 1 % of tumour cells ) , which was measured with the 73 - 10 assay , and histology ( squamous vs non-squamous ) . The primary endpoint was overall survival , analysed when roughly 337 events ( deaths ) had occurred in the PD-L1-positive population . Efficacy was analysed in all PD-L1-positive patients ( ie , PD-L1 expression in ≥1 % of tumour cells ) r and omly assigned to study treatment ( the primary analysis population ) and then in all r and omly assigned patients through a hierarchical testing procedure . Safety was analysed in all patients who received at least one dose of study treatment . This trial is registered with Clinical Trials.gov , number NCT02395172 . Enrolment is complete , but the trial is ongoing . FINDINGS Between March 24 , 2015 , and Jan 23 , 2017 , 792 patients were enrolled and r and omly assigned to receive avelumab ( n=396 ) or docetaxel ( n=396 ) . 264 participants in the avelumab group and 265 in the docetaxel group had PD-L1-positive tumours . In patients with PD-L1-positive tumours , median overall survival did not differ significantly between the avelumab and docetaxel groups ( 11·4 months [ 95 % CI 9·4 - 13·9 ] vs 10·3 months [ 8·5 - 13·0 ] ; hazard ratio 0·90 [ 96 % CI 0·72 - 1·12 ] ; one-sided p=0·16 ) . Treatment-related adverse events occurred in 251 ( 64 % ) of 393 avelumab-treated patients and 313 ( 86 % ) of 365 docetaxel-treated patients , including grade 3 - 5 events in 39 ( 10 % ) and 180 ( 49 % ) patients , respectively . The most common grade 3 - 5 treatment-related adverse events were infusion-related reaction ( six patients [ 2 % ] ) and increased lipase ( four [ 1 % ] ) in the avelumab group and neutropenia ( 51 [ 14 % ] ) , febrile neutropenia ( 37 [ 10 % ] ) , and decreased neutrophil counts ( 36 [ 10 % ] ) in the docetaxel group . Serious treatment-related adverse events occurred in 34 ( 9 % ) patients in the avelumab group and 75 ( 21 % ) in the docetaxel group . Treatment-related deaths occurred in four ( 1 % ) participants in the avelumab group , two due to interstitial lung disease , one due to acute kidney injury , and one due to a combination of autoimmune myocarditis , acute cardiac failure , and respiratory failure . Treatment-related deaths occurred in 14 ( 4 % ) patients in the docetaxel group , three due to pneumonia , and one each due to febrile neutropenia , septic shock , febrile neutropenia with septic shock , acute respiratory failure , cardiovascular insufficiency , renal impairment , leucopenia with mucosal inflammation and pyrexia , infection , neutropenic infection , dehydration , and unknown causes . INTERPRETATION Compared with docetaxel , avelumab did not improve overall survival in patients with platinum-treated PD-L1-positive NSCLC , but had a favourable safety profile . FUNDING Merck and Pfizer BACKGROUND An earlier analysis in this phase 3 trial showed that durvalumab significantly prolonged progression‐free survival , as compared with placebo , among patients with stage III , unresectable non – small‐cell lung cancer ( NSCLC ) who did not have disease progression after concurrent chemoradiotherapy . Here we report the results for the second primary end point of overall survival . METHODS We r and omly assigned patients , in a 2:1 ratio , to receive durvalumab intravenously , at a dose of 10 mg per kilogram of body weight , or matching placebo every 2 weeks for up to 12 months . R and omization occurred 1 to 42 days after the patients had received chemoradiotherapy and was stratified according to age , sex , and smoking history . The primary end points were progression‐free survival ( as assessed by blinded independent central review ) and overall survival . Secondary end points included the time to death or distant metastasis , the time to second progression , and safety . RESULTS Of the 713 patients who underwent r and omization , 709 received the assigned intervention ( 473 patients received durvalumab and 236 received placebo ) . As of March 22 , 2018 , the median follow‐up was 25.2 months . The 24‐month overall survival rate was 66.3 % ( 95 % confidence interval [ CI ] , 61.7 to 70.4 ) in the durvalumab group , as compared with 55.6 % ( 95 % CI , 48.9 to 61.8 ) in the placebo group ( two‐sided P=0.005 ) . Durvalumab significantly prolonged overall survival , as compared with placebo ( stratified hazard ratio for death , 0.68 ; 99.73 % CI , 0.47 to 0.997 ; P=0.0025 ) . Up date d analyses regarding progression‐free survival were similar to those previously reported , with a median duration of 17.2 months in the durvalumab group and 5.6 months in the placebo group ( stratified hazard ratio for disease progression or death , 0.51 ; 95 % CI , 0.41 to 0.63 ) . The median time to death or distant metastasis was 28.3 months in the durvalumab group and 16.2 months in the placebo group ( stratified hazard ratio , 0.53 ; 95 % CI , 0.41 to 0.68 ) . A total of 30.5 % of the patients in the durvalumab group and 26.1 % of those in the placebo group had grade 3 or 4 adverse events of any cause ; 15.4 % and 9.8 % of the patients , respectively , discontinued the trial regimen because of adverse events . CONCLUSIONS Durvalumab therapy result ed in significantly longer overall survival than placebo . No new safety signals were identified . ( Funded by AstraZeneca ; PACIFIC Clinical Trials.gov number , NCT02125461 . Significance Programmed death-lig and 1 ( PD-L1 ) expression on tumor cells and tumor-infiltrating immune cells is regulated by distinct mechanisms and has nonredundant roles in regulating anticancer immunity , and PD-L1 on both cell types is important for predicting best response to atezolizumab in non-small cell lung cancer . Programmed death-lig and 1 ( PD-L1 ) expression on tumor cells ( TCs ) by immunohistochemistry is rapidly gaining importance as a diagnostic for the selection or stratification of patients with non-small cell lung cancer ( NSCLC ) most likely to respond to single-agent checkpoint inhibitors . However , at least two distinct patterns of PD-L1 expression have been observed with potential biological and clinical relevance in NSCLC : expression on TC or on tumor-infiltrating immune cells ( ICs ) . We investigated the molecular and cellular characteristics associated with PD-L1 expression in these distinct cell compartments in 4,549 cases of NSCLC . PD-L1 expression on IC was more prevalent and likely reflected IFN-γ – induced adaptive regulation accompanied by increased tumor-infiltrating lymphocytes and effector T cells . High PD-L1 expression on TC , however , reflected an epigenetic dysregulation of the PD-L1 gene and was associated with a distinct histology described by poor immune infiltration , sclerotic/desmoplastic stroma , and mesenchymal molecular features . Importantly , durable clinical responses to atezolizumab ( anti – PD-L1 ) were observed in patients with tumors expressing high PD-L1 levels on either TC alone [ 40 % objective response rate ( ORR ) ] or IC alone ( 22 % ORR ) . Thus , PD-L1 expression on TC or IC can independently attenuate anticancer immunity and emphasizes the functional importance of IC in regulating the antitumor T cell response BACKGROUND The programmed death 1 ( PD-1 ) receptor is a negative regulator of T-cell effector mechanisms that limits immune responses against cancer . We tested the anti-PD-1 antibody lambrolizumab ( previously known as MK-3475 ) in patients with advanced melanoma . METHODS We administered lambrolizumab intravenously at a dose of 10 mg per kilogram of body weight every 2 or 3 weeks or 2 mg per kilogram every 3 weeks in patients with advanced melanoma , both those who had received prior treatment with the immune checkpoint inhibitor ipilimumab and those who had not . Tumor responses were assessed every 12 weeks . RESULTS A total of 135 patients with advanced melanoma were treated . Common adverse events attributed to treatment were fatigue , rash , pruritus , and diarrhea ; most of the adverse events were low grade . The confirmed response rate across all dose cohorts , evaluated by central radiologic review according to the Response Evaluation Criteria in Solid Tumors ( RECIST ) , version 1.1 , was 38 % ( 95 % confidence interval [ CI ] , 25 to 44 ) , with the highest confirmed response rate observed in the cohort that received 10 mg per kilogram every 2 weeks ( 52 % ; 95 % CI , 38 to 66 ) . The response rate did not differ significantly between patients who had received prior ipilimumab treatment and those who had not ( confirmed response rate , 38 % [ 95 % CI , 23 to 55 ] and 37 % [ 95 % CI , 26 to 49 ] , respectively ) . Responses were durable in the majority of patients ( median follow-up , 11 months among patients who had a response ) ; 81 % of the patients who had a response ( 42 of 52 ) were still receiving treatment at the time of analysis in March 2013 . The overall median progression-free survival among the 135 patients was longer than 7 months . CONCLUSIONS In patients with advanced melanoma , including those who had had disease progression while they had been receiving ipilimumab , treatment with lambrolizumab result ed in a high rate of sustained tumor regression , with mainly grade 1 or 2 toxic effects . ( Funded by Merck Sharp and Dohme ; Clinical Trials.gov number , NCT01295827 . ) BACKGROUND Erlotinib is registered for treatment of all patients with advanced non-small-cell lung cancer ( NSCLC ) . However , its efficacy for treatment of patients whose tumours are EGFR wild-type-which includes most patients -is still contentious . We assessed the efficacy of erlotinib compared with a st and ard second-line chemotherapy in such patients . METHODS We did this r and omised controlled trial in 52 Italian hospitals . We enrolled patients who had metastatic NSCLC , had had platinum-based chemotherapy , and had wild-type EGFR as assessed by direct sequencing . Patients were r and omly assigned central ly ( 1:1 ) to receive either erlotinib orally 150 mg/day or docetaxel intravenously 75 mg/m(2 ) every 21 days or 35 mg/m(2 ) on days 1 , 8 , and 15 , every 28 days . R and omisation was stratified by centre , stage , type of first-line chemotherapy , and performance status . Patients and investigators who gave treatments or assessed outcomes were not masked to treatment allocation , investigators who analysed results were . The primary endpoint was overall survival in the intention-to-treat population . The study is registered at Clinical Trials.gov , number NCT00637910 . FINDINGS We screened 702 patients , of whom we genotyped 540 . 222 patients were enrolled ( 110 assigned to docetaxel vs 112 assigned to erlotinib ) . Median overall survival was 8·2 months ( 95 % CI 5·8 - 10·9 ) with docetaxel versus 5·4 months ( 4·5 - 6·8 ) with erlotinib ( adjusted hazard ratio [ HR ] 0·73 , 95 % CI 0·53 - 1·00 ; p=0·05 ) . Progression-free survival was significantly better with docetaxel than with erlotinib : median progression-free survival was 2·9 months ( 95 % CI 2·4 - 3·8 ) with docetaxel versus 2·4 months ( 2·1 - 2·6 ) with erlotinib ( adjusted HR 0·71 , 95 % CI 0·53 - 0·95 ; p=0·02 ) . The most common grade 3 - 4 toxic effects were : low absolute neutrophil count ( 21 [ 20 % ] of 104 in the docetaxel group vs none of 107 in the erlotinib group ) , skin toxic effects ( none vs 15 [ 14 % ] ) , and asthenia ( ten [ 10 % ] vs six [ 6 % ] ) . INTERPRETATION Our results show that chemotherapy is more effective than erlotinib for second-line treatment for previously treated patients with NSCLC who have wild-type EGFR tumours BACKGROUND Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes . We assessed the activity of nivolumab , a fully human IgG4 PD-1 immune checkpoint inhibitor antibody , for patients with advanced , refractory , squamous non-small-cell lung cancer . METHODS We did this phase 2 , single-arm trial at 27 sites ( academic , hospital , and private cancer centres ) in France , Germany , Italy , and USA . Patients who had received two or more previous treatments received intravenous nivolumab ( 3 mg/kg ) every 2 weeks until progression or unacceptable toxic effects . The primary endpoint was the proportion of patients with a confirmed objective response as assessed by an independent radiology review committee . We included all treated patients in the analyses . This study is registered with Clinical Trials.gov , number NCT01721759 . FINDINGS Between Nov 16 , 2012 , and July 22 , 2013 , we enrolled and treated 117 patients . 17 ( 14·5 % , 95 % CI 8·7 - 22·2 ) of 117 patients had an objective response as assessed by an independent radiology review committee . Median time to response was 3·3 months ( IQR 2·2 - 4·8 ) , and median duration of response was not reached ( 95 % CI 8·31-not applicable ) ; 13 ( 77 % ) of 17 of responses were ongoing at the time of analysis . 30 ( 26 % ) of 117 patients had stable disease ( median duration 6·0 months , 95 % CI 4·7 - 10·9 ) . 20 ( 17 % ) of 117 patients reported grade 3 - 4 treatment-related adverse events , including : fatigue ( five [ 4 % ] of 117 patients ) , pneumonitis ( four [ 3 % ] ) , and diarrhoea ( three [ 3 % ] ) . There were two treatment-associated deaths caused by pneumonia and ischaemic stroke that occurred in patients with multiple comorbidities in the setting of progressive disease . INTERPRETATION Nivolumab has clinical ly meaningful activity and a manageable safety profile in previously treated patients with advanced , refractory , squamous non-small cell lung cancer . These data support the assessment of nivolumab in r and omised , controlled , phase 3 studies of first-line and second-line treatment . FUNDING Bristol-Myers Squibb |
12,915 | 31,486,984 | This review supports the assertion that TTA can be considered a measure of quality of care , emphasizes the importance of education and training , and describes the very different interventions which have effectively reduced TTA | Multiple interventions have been developed aim ing to reduce time to antibiotics ( TTA ) in patients with fever and neutropenia ( FN ) following chemotherapy for cancer .
We evaluated their effect to reduce TTA and their impact on important clinical outcomes in a systematic review . | ABSTRACT The time to antibiotic administration ( TTA ) has been proposed as a quality -of-care measure in febrile neutropenia ( FN ) ; however , few data regarding the impact of the TTA on the mortality of adult cancer patients with FN are available . The objective of this study was to determine whether the TTA is a predictor of mortality in adult cancer patients with FN . A prospect i ve cohort study of all consecutive cases of FN , evaluated from October 2009 to August 2011 , at a single tertiary referral hospital in southern Brazil was performed . The TTA was assessed as a predictive factor for mortality within 28 days of FN onset using the Cox proportional hazards model . Kaplan-Meier curves were used for an assessment of the mortality rates according to different TTAs ; the log-rank test was used for between-group comparisons . In total , 307 cases of FN ( 169 subjects ) were evaluated . During the study period , there were 29 deaths . In a Cox regression analysis , the TTA was independently associated with mortality within 28 days ( hazard ratio [ HR ] , 1.18 ; 95 % confidence interval [ CI ] , 1.10 to 1.26 ) ; each increase of 1 h in the TTA raised the risk of mortality within 28 days by 18 % . Patients with FN episodes with a TTA of ≤30 min had lower 28-day mortality rates than those with a TTA of between 31 min and 60 min ( 3.0 % versus 18.1 % ; log-rank P = 0.0002 ) . Early antibiotic administration was associated with higher survival rates in the context of FN . Efforts should be made to ensure that FN patients receive effective antibiotic therapy as soon as possible . A target of 30 min to the TTA should be adopted for cancer patients with FN Background : Early administration of antimicrobial ( AM ) is relevant in children with cancer , fever and neutropenia ( FN ) . The recommendation is to administer the first dose of AM within the first hour of hospital admission . Our aims were to determine the time from the moment that a child with FN is admitted to the hospital until they receive their first dose of AM and to determine the association with clinical outcomes . Methods : This prospect i ve , multicenter study evaluated the time elapsed from the admission to the first dose of AM , comparing this variable by admitting hospital and presentation location ( Emergency Department/Oncology Units ) and evaluating the clinical outcomes by the following variables : days of fever , days of hospitalization , hypotension , transfer to intensive care unit , sepsis and mortality . Results : A total of 226 children with 388 episodes of FN were enrolled from 5 hospitals ( July 2012–April 2014 ) . The median time between hospital admission and administration of the first dose of AM was 132 minutes ( interquartile range : 60–246 minutes ) . The median time to AM administration was significantly different between hospitals ( 70 vs. 200 minutes , P < 0.0001 ) and between presentation locations ( Emergency Department vs. Oncology Units , median : 200 vs. 100 minutes , P < 0.0001 ) . Twenty-five percentage of children received AM within 1 hour of admission . The administration of AM after 60 minutes was not associated with worse outcomes . Conclusions : Time to AM administration was longer than the recommendation . The findings described provide an opportunity to identify gaps and implement programs aim ed at improving the equity and excellence of care in children with cancer and FN Background Antibiotic delivery to patients with fever and neutropenia ( F&N ) in < 60 min is an increasingly important quality measure for oncology centers , but several published reports indicate that a time to antibiotic delivery ( TTA ) of < 60 min is quite difficult to achieve . Here we report a quality improvement ( QI ) effort that sought to decrease TTA and assess associated clinical outcomes in pediatric patients with cancer and F&N. Procedure We used Lean- Methodology and a Plan-Do- Study -Act approach to direct QI efforts and prospect ively tracked TTA measures and associated clinical outcomes ( length of stay , duration of fever , use of imaging studies to search for occult infection , bacteremia , intensive care unit ( ICU ) consultation or admission , and mortality ) . We then performed statistical analysis to determine the impact of our QI interventions on total TTA , sub-process times , and clinical outcomes . Results Our QI interventions significantly improved TTA such that we are now able to deliver antibiotics in < 60 min nearly 100 % of the time . All TTA sub-process times also improved . Moreover , achieving TTA < 60 min significantly reduced the need for ICU consultation or admission ( P = 0.003 ) in this population . Conclusion Here we describe our QI effort along with a detailed assessment of several associated clinical outcomes . These data indicate that decreasing TTA to < 60 min is achievable and associated with improved outcomes in pediatric patients with cancer and 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 Children with cancer and fever are at high risk for sepsis related death . Rapid antibiotic delivery ( < 60 minutes ) has been shown to reduce mortality . We compared patient outcomes and describe interventions from three separate quality improvement ( QI ) projects conducted in three United States ( US ) tertiary care pediatric emergency departments ( EDs ) with the shared aim to reduce time to antibiotic ( TTA ) to < 60 minutes in febrile pediatric oncology patients ( Temperature > 38.0 C ) . A secondary objective was to identify interventions amenable to translation to other centers . We conducted a post project analysis of prospect ively collected observational data from children < 18 years visiting these EDs during independently conducted QI projects . Comparisons were made pre to post intervention periods within each institution . All interventions were derived independently using QI methods by each institution . Successful as well as unsuccessful interventions were described and common interventions adopted by all sites identified . A total of 1032 ED patient visits were identified from the three projects . Improvement in median TTA delivery ( min ) pre to post intervention(s ) was 118.5–57.0 at site 1 , 163.0–97.5 at site 2 , and 188.0–111.5 at site 3 ( p<.001 all sites ) . The eight common interventions were 1 ) Triage application of topical anesthetic 2 ) Rapid room placement & triage 3 ) Resuscitation room placement of ill appearing children 4 ) Close proximity to central line equipment 5 ) Antibiotic administration before laboratory analyses 6 ) Consensus clinical practice guideline establishment 7 ) Family pre-ED education for fever and 8) Staff project up date s. This core set of eight low cost , high yield QI interventions were developed independently by the three ED 's which led to substantial reduction in time to antibiotic delivery in children with cancer presenting with fever . These interventions may inform future QI initiatives in other setting s caring for febrile pediatric oncology patients PURPOSE Febrile neutropenia ( FN ) is an oncologic emergency , and prolonged time to antibiotic administration ( TTA ) is associated with increased hospital length of stay ( LOS ) and worse outcomes . We hypothesized that a febrile neutropenia pathway ( FNP ) quality initiative project would reduce TTA delays for febrile patients with cancer presenting to the emergency department ( ED ) . METHODS This prospect i ve study compared ED FNP patients ( > 18 years old ) , between June 2012 and June 2013 with both historical and direct admissions ( DA ) cohorts at a multispecialty academic center . Interventions included providing patients with FN-Alert cards , st and ardizing the definition of FN and recognizing it as a distinct chief complaint , revising ED triage level for FN , creating electronic FN order sets , administering empiric antibiotics before neutrophil count result , and relocating FN antibiotics to the ED . The primary outcome was TTA , with a target goal of 90 minutes after ED presentation . RESULTS In total , 276 FN episodes in 223 FNP patients occurred over the 12-month study period and were compared with 107 episodes in 87 patients and 114 episodes in 101 patients in the historical and DA cohorts , respectively . Use of the FNP reduced TTA from 235 and 169 minutes in historical and DA cohorts , respectively , to 81 minutes , and from 96 to 68 minutes when the order set was not used versus used in the FNP group ( P < .001 for all comparisons ) . Decrease in hospital LOS was not statistically significant . CONCLUSION The ED FNP is a significant quality initiative with sustainable interventions , and was able to demonstrate value by decreasing TTA compared to both historical and DA controls in cancer patients presenting to the ED BACKGROUND Time-to-antibiotic ( TTA ) administration is a widely used quality -of-care measure for children with cancer and febrile neutropenia ( FN ) . We sought to determine whether TTA is associated with outcomes of FN . PROCEDURE A single-center , retrospective cohort study was conducted of 1,628 FN admissions from 653 patients from 2001 to 2009 . Outcome variables included ( 1 ) an adverse event ( AE ) composite of in-hospital mortality , pediatric intensive care unit ( PICU ) admission within 24 hours of presentation , and /or fluid resuscitation ≥ 40 ml/kg within 24 hours of presentation and ( 2 ) length of stay ( LOS ) . TTA was measured as a continuous variable and in 60-minute intervals . Mixed regression models were constructed to evaluate associations of TTA with the outcome variables after adjusting for relevant covariates including cancer diagnosis , degree of myelosuppression , and presence of bacteremia . RESULTS The composite AE outcome occurred in 11.1 % of admissions including 0.7 % in-hospital mortality , 4.7 % PICU admission , and 10.1 % fluid resuscitation . In univariate analysis , TTA was associated with the composite AE outcome ( Odds Ratio [ OR ] 1.29 , 95 % CI 1.02 - 1.64 ) but not LOS . In multivariate analysis , after adjustment for relevant covariates , 60-minute TTA intervals were associated with the composite AE outcome ( 61 - 120 minutes vs. ≤ 60 minutes , OR 1.81 , 95 % CI 1.01 - 3.26 ) . Unexpectedly , admission from the emergency department ( ED ) was also independently associated with the composite AE outcome ( ED vs. clinic , OR 3.15 , 95 % CI 1.95 - 5.09 ) . CONCLUSIONS TTA and presentation to the ED are independently associated with poor outcomes of FN Objectives Patients with febrile neutropenia are at high risk of morbidity and mortality from infectious causes . Decreasing time to antibiotic ( TTA ) administration is associated with improved patient outcomes . We sought to reduce TTA for children presenting to the emergency department with fever and neutropenia . Methods In a prospect i ve cohort study with historical comparison , TTA administration was evaluated in patients with neutropenia presenting to the Children 's of Alabama Emergency Department . A protocol was established to reduce delays in antibiotic administration and increase the percentage of patients who receive treatment within 60 minutes of presentation . One hundred pre- protocol patient visits between August 2010 and December 2011 were evaluated and 153 post- protocol visits were evaluated between August 2012 and September 2013 . We review ed individual cases to determine barriers to rapid antibiotic administration . Results Antibiotics were administered in 96.9 ± 57.8 minutes in the pre- protocol patient group , and only 35 % of patients received antibiotics within 60 minutes of presentation and 70 % received antibiotics within 120 minutes . After implementation of the protocol , TTA for neutropenic patients was decreased to 64.3 ± 28.4 minutes ( P < 0.0001 ) with 51.4 % receiving antibiotics within 60 minutes and 93.2 % within 120 minutes . Conclusions Implementing a st and ard approach to patients at risk for neutropenia decreased TTA . There are numerous challenges in providing timely antibiotics to children with febrile neutropenia . Identified delays included venous access ( time to effect of topical anesthetics , and difficulty obtaining access ) , physicians waiting on laboratory results , and antibiotic availability BACKGROUND Fever and chemotherapy-induced neutropenia ( FN ) is the most frequent potentially lethal complication of therapy in children with cancer . This study aim ed to describe serious medical complications ( SMC ) in children with FN regarding incidence , clinical spectrum , and associated characteristics . PROCEDURE Pediatric patients presenting with FN induced by non-myeloablative chemotherapy were observed in a prospect i ve multicenter study . SMC was defined as potentially life-threatening complication ( PLTC ) , transfer to the pediatric intensive care unit ( PICU ) , or death . RESULTS A total of 443 FN episodes were reported from 8 centers . Of these , 411 episodes were reported from 4 centers recruiting consecutively and without bias regarding the risk of complications . They were used for calculation of proportions . An SMC was reported in 23 episodes [ 5.6 % ; 95 % confidence interval ( CI ) : 3.7 - 8.1 ] , usually defined by more than one criterion . These were PLTC in 13 episodes , PICU in 22 , and death in 3 ( mortality , 0.7 % ; 95 % CI : 0.2 - 2.1 ) . Both a delayed onset of SMC ( 14 of 23 episodes , 61 % ) and a biphasic clinical course ( 11 of 23 , 48 % ) were frequently observed . In a multivariate logistic regression analysis , 4 characteristics were significantly and independently associated with the risk of SMC : diagnosis of acute myeloid leukemia , interval since chemotherapy ≤7 days , severely reduced general condition , and hemoglobin ≥9.0 g/dl at presentation . CONCLUSIONS In children with FN , SMC were rare , and mortality was very low . Those with SMC often had a delayed onset and biphasic clinical course with secondary deterioration Background Fever and neutropenia ( FN ) is a common complication of chemotherapy for cancer . Prompt empiric broad-spectrum antibiotic therapy in FN is typically considered st and ard of care , but the definition of prompt is not clear . We seek to systematic ally review the available data on the association between time to antibiotics ( TTA ) administration and clinical outcomes in patients with FN being treated with chemotherapy . There have been several efforts to reduce TTA in patients with FN , by implementing specific interventions , presuming there will be a beneficial effect on patient-important outcomes . This systematic review will also collect data on such interventions and their effect to reduce TTA and potentially change clinical outcomes . Methods / design The search will cover MEDLINE , MEDLINE In-Process & Other Non-Indexed Citations , EMBASE , CINAHL , CDSR , CENTRAL , and LILACS . A full- search strategy is provided . Lists of studies identified by references cited and forward citation search ing of included articles will also be review ed . Studies will be screened , and data extracted by one research er and independently checked by a second . Confounding biases and quality of studies will be assessed with the risk of bias in non-r and omised studies -of interventions ( ROBINS-I ) tool . Data will be presented in narrative and tabular forms ; in addition , if appropriate data is available , r and om effects meta- analysis will be used to examine TTA.A detailed analysis plan , including an assessment of heterogeneity and publication bias , is provided . Discussion This study aims to evaluate the association between TTA and patient-important clinical outcomes . Additionally , it will identify , critically appraise , and synthesis e information on performed interventions and its effect to reduce TTA as a way of gaining insight into the potential use of these approaches . This will provide better knowledge for an adjusted treatment approach of FN . Systematic review registration PROSPERO [ CRD42018092948 |
12,916 | 18,254,092 | Analysis of these studies showed that , although the primary outcome of PDA closure on days two and five slightly favored bolus administration , there was no statistical difference between the two groups .
AUTHORS ' CONCLUSIONS Due to a paucity of events and lack of precision , the available data was found to be insufficient to draw conclusions regarding the efficacy of continuous indomethacin infusion versus bolus injections for the treatment of PDA .
Although continuous indomethacin seems to cause less alterations in cerebral , renal and mesenteric circulations , the clinical meaning of this effect is unclear . | BACKGROUND Indomethacin is a prostagl and in inhibitor used for the prevention and the treatment of patent ductus arteriosus ( PDA ) .
Although a 3-dose schedule has been commonly used , there is no consensus on optimal dosage and duration of indomethacin therapy for PDA closure .
There are potential adverse effects of indomethacin use in premature infants such as a reduction in cerebral , mesenteric and renal blood flow and platelet dysfunction .
Administering indomethacin continuously over 36-hours has been suggested as a safer and more effective option to prevent such adverse effects .
OBJECTIVES To compare the efficacy and safety of continuous infusion versus bolus administration of indomethacin in closing a symptomatic PDA in preterm infants . | 1 . Shackelford GD . Neurosonography of hydrocephalus in infants . Neuroradiology 1986;28:452 - 62 . 2 . Levene MI . Measurement of the growth of the lateral ventricles in preterm infants with real-time ultrasound . Arch Dis Child 1981 ; 56i900 - 4 . 3 . Johnson ML , Mack LA , Rumaek CM , et al. B-mode echoencephalography inthe normal and high risk infant . A JR Am J Roentgenol 1979;133:374 - 81 . 4 . Rumack CM , Johnson ML . Perinatal and infant brain imaging . Chicago : Year Book Medical Publishers , 1984:157 . 5 . Brann BS , Wofsy C , Wicks J , Brayer J. The quantification of neonatal cerebral ventricular volume by real-time ultrasonography : derivation and in vitro confirmation of a mathematical model . J Ultrasound Med 1990;9:1 - 8 . 6 . Brann BS , Wofsy C , Papile LA , Angelus P , Backstrom C. The quantification of neonatal cerebral ventricular volume by realtime ultrasonography : in vivo validation of the cylindrical coordinate method . J Ultrasound Med 1990;9:9 - 15 . 7 . Garrett W J , Kossoff G , Warren PS . Cerebral ventricular size in children : a two-dimensional ultrasonic study . Radiology 1980 ; 136:711 - 5 . 8 . London DA , Carroll BA , Enzmann DR . Sonography of ventricular size and germinal matrix hemorrhage in premature infants . AJNR 1980;1:295 - 300 . 9 . Sauerbrei EE , Digney M , Harrison PB , Cooperberg PL . Ultrasonic evaluation of neonatal intracranial hemorrhage and its complications . Radiology 1981 ; 39:667 - 85 . 10 . Quisling RG , Reeder JD , Setzer ES , Kaude JV . Temporal comparative analysis of computed tomography with ultrasound for intracranial hemorrhage in premature infants . Neuroradiology 1983;24:205 - 11 . 11 . Naidich TP , Epstein F , Lin JP , Kricheff II , Hochwald GM . Evaluation Of pediatric hydrocephalus by computed tomography . Radiology 1976;119:337 - 45 . 12 . Hertzberg BS , Bowie JD , Burger PC , Marshburn PB , Djang WT . The th?ee lines : origin of sonographic l and marks in the fetal head . A JR Am J Roentgenol 1987;149:1009 - 12 . 13 . Hakim S , Adams RD . The special clinical problem of symptomatic hydrocephalus with normal cerebrospinal fluid pressure . J Neurol Sci 1965;2:307 - 27 . 14 . Geschwind N. The mechanism of normal pressure hydrocephalus . J Neurol Sci 1968;7:481 - 93 . 15 . Nagashima T , Tamaki N , Matsumoto S , Horwitz B , Seguchi Y. Biomechanics of hydrocephalus : a new theoretical model . Neurosurgery 1987;21:898 - 904 As a result of r and omized assignment , 15 preterm infants weighing 1,500 gm or less at birth and who had a symptomatic PDA were treated according to a medical management protocol , and ten according to an early surgical closure protocol . All infants required mechanical ventilation at the time of study entry , which was one week after birth . Birth weight , gestational age , age at onset of congestive failure , age at study entry , and the initial morbidity of members of the two groups were similar . The nine surviving infants managed according to the surgical closure protocol were weaned from mechanical ventilation sooner , had a decreased need for digoxin and furosemide , achieved gastrointestinal function sooner , and had a smaller hospital bill than the 12 survivors of the medical management group . These results indicate that infants with a symptomatic PDA still requiring mechanical ventilation at one week after birth will benefit from surgical closure of the ductus at that time AIM To evaluate the efficiency and side effects of ibuprofen for the early treatment of patent ductus arteriosus ( PDA ) and compare it with indomethacin . METHODS Forty preterm infants with gestational ages of less than 33 weeks , with respiratory distress syndrome ( RDS ) and echocardiographically confirmed PDA , were r and omly assigned at days 2 to 3 of life to receive either intravenous indomethacin 3 × 0.2 mg/kg at 12 hour intervals or intravenous ibuprofen 1 × 10 mg/kg , followed by 5 mg/kg 24 and 48 hours later . RESULTS PDA closed in 15 of 20 patients from the indomethacin group ( 75 % ) and in 16 of 20 ( 80 % ) from the ibuprofen group . Seven patients ( three indomethacin , four ibuprofen ) required a second treatment with indomethacin and in five ( three in the indomethacin group and two in the ibuprofen group ) the duct was ultimately ligated . Ibuprofen patients had a better urinary output and showed no increase in serum creatinine concentrations compared with the indomethacin group . Ibuprofen was not associated with any other side effect . CONCLUSIONS Ibuprofen treatment seems to be as efficient as indomethacin in closing PDA on the third day of life in preterm infants with respiratory distress syndrome and seems to have fewer renal side effects We admitted 36 preterm neonates ( 600 to 1250 gm birth weight ) with normal 6-hour echoencephalograms to a r and omized , placebo-controlled prospect i ve trial to determine whether a low dose of indomethacin would prevent germinal matrix or intraventricular hemorrhage and permit adequate urinary output . Between the sixth and tenth postnatal hours , indomethacin ( 0.1 mg/kg ) or placebo was administered intravenously every 24 hours for a total of three doses . Cardiac ultrasound studies to assess the status of the ductus arteriosus were performed at 6 postnatal hours and on day 5 . Urinary output , serum electrolytes , serum indomethacin levels , and renal and clotting functions were monitored . No differences in birth weight , gestational age , or Apgar scores were noted between the two groups of infants . Two indomethacin-treated infants and three infants given placebo had significant urinary output difficulties , requiring that the study medication be withheld . Of 19 infants given indomethacin , two had germinal matrix or intraventricular hemorrhage , in comparison with 8 of 17 infants given saline solution ( p = 0.02 ) . Of the infants who had a left-to-right patent ductus arteriosus shunt before treatment , 64 % of the indomethacin-treated and 33 % of the saline solution-treated infants no longer had a patent ductus arteriosus on day 5 . Ductal status appeared unrelated to the development of germinal matrix or intraventricular hemorrhage Objectives To determine patent ductus arteriosus ( PDA ) closure rates , and indomethacin ( INDO ) toxicity rates in neonates dosed with INDO using an individualized pharmacokinetic/pharmacodynamic ( PK/PD ) dosing approach . In addition , develop PD curves evaluating dose-response and concentration-response relationships for closure and renal toxicity , especially in select subgroups historically known as “ poor responders ” ( < 1000 g and ≥10 days postnatal age ) . Design Prospect i ve , cohort study . Setting Level III neonatal intensive care unit . Subjects One hundred thirty-nine patients receiving 151 courses of INDO for PDA closure were evaluated . Interventions Patients initially received 0.25 mg/kg of INDO , followed immediately by 1 mg/kg of furosemide . INDO concentrations were obtained 2 hrs and 8 hrs after the dose and were assayed using high-performance liquid chromatography . Individualized PK parameters were calculated with subsequent INDO dosing based on the individualized PK variables to increase trough serum concentrations by 0.3–0.5 mg/L. Measurements and Main Results Ductal closure was successful in 127 patients ( 91 % ) . Renal toxicity occurred in 21 ( 15 % ) patients and was temporary and reversible . No significant differences in response rates based on treatment weight or postnatal age were observed . PD curves were similar for neonates < 1000 g vs. ≥1000 g. PD curves were also similar for neonates with postnatal age < 10 days vs. ≥10 days . Statistically significant differences were noted between neonates categorized for postnatal age < 10 days vs. ≥ 10 days in total days of therapy ( 1.8 vs. 2.3 days ) , total number of doses required to close PDA ( 3.5 vs. 5.6 doses ) , critical INDO dose ( 0.9 vs. 1.4 mg/kg ) , critical INDO concentration ( 1.9 vs. 1.4 mg/L ) , and critical dose/critical concentration ratio ( 0.52 vs. 2.2 ) . Conclusions These findings support the hypothesis that the poor PDA closure rates with INDO for neonates > 10 days postnatal age are the result of pharmacokinetic differences only and that weight does not impact response rates . Individualized pharmacokinetic/pharmacodynamic dosing of INDO continues to achieve higher closure rate than current dosing st and ards . Patients historically known as poor responders significantly benefit from this dosing approach In a r and omized study , indomethacin was administered either by an intravenous rapid infusion or by a 30-minute intravenous infusion to preterm infants . Ten infants were r and omly assigned to the rapid infusion group and nine to the other group . Time-averaged mean systolic , mean flow velocity , and mean diastolic blood flow velocities were measured in the internal carotid artery with a pulsed Doppler . Blood flow velocities , arterial blood gases , intraarterial blood pressures , and transcutaneous PO2 and PCO2 were measured at 5 and 1 minutes before indomethacin and then at 5 , 10 , 20 , 30 , 35 , 40 , 50 , 60 , and 90 minutes after indomethacin administration . Intravenous indomethacin either by rapid or slow infusion caused a significant decrease in the blood flow velocities . The blood flow velocities were significantly lower 5 minutes after rapid infusion and by 30 minutes in the slow-infusion group . In both groups , the blood flow velocities remained depressed up to 90 minutes . The blood pressures increased concomitantly to the blood flow velocities in the rapid-administration group only . Because indomethacin given for 30 minutes does not avoid the decrease in the blood flow velocities , further studies are necessary to ascertain the safest method of administration Abstract . Indomethacin ( INDO ) and , more recently , ibuprofen ( IBU ) have been used to treat haemodynamically significant patent ductus arteriosus ( PDA ) in preterm infants . Both are cyclo-oxygenase blockers , but seem to have a different influence on regional circulation . In a prospect i ve , r and omised , controlled study , we compared INDO and IBU with regard to efficacy and safety for the early non-invasive treatment of PDA . Doppler echocardiography was used to study 232 preterm infants ( gestational age 23–34 weeks ) with respiratory distress syndrome of whom 175 had persistent , haemodynamically significant PDA at 48–72 h of life . They were r and omised to receive three intravenous doses of either INDO ( 0.2 mg/kg , at 12 h intervals ) or IBU ( a first 10 mg/kg dose followed by two doses of 5 mg/kg at 24 h intervals ) , recording rate of ductal closure , need for additional treatment , side-effects and clinical course . The efficacy of the pharmacological treatment was similar in the two groups ( 56/81 , 69 % INDO ; 69/94 , 73 % IBU ) . Patients treated with INDO showed a significant increase in serum creatinine ( 89±24 versus 82±20 mmol/l , P=0.03 ) and a near-significant tendency for a lower fractional excretion of sodium ( 3±3 versus 4±2 % , P=0.08 ) ; moreover , 12/81 ( 15 % ) INDO patients versus 1/94 ( 1 % ) IBU patients became oliguric ( < 1 ml/kg per h ) during treatment ( P=0.017 ) . Conclusion : our findings confirm that , by comparison with indomethacin , ibuprofen has fewer effects on renal function in terms of urine output and fluid retention , with much the same efficacy and safety in closing patent ductus arteriosus in preterm infants with respiratory distress syndrome . In particular , no increased incidence of intracranial haemorrhage was observed after ibuprofen treatment OBJECTIVE Therapeutic administration of indomethacin for patent ductus arteriosus ( PDA ) closure has been documented to decrease cerebral blood flow velocity which may be harmful to the vulnerable premature neonate . We have therefore compared the effects of administering indomethacin by rapid injection versus slow , continuous indomethacin infusion at the same total therapeutic dose on middle cerebral artery ( MCA ) systolic and diastolic flow velocity , resistance index , and cerebral blood flow ( as reflected by the integrated area under the curve ) . METHODS Premature neonates ( < 1750 g ) documented echocardiographically to have a PDA were r and omized to receive indomethacin either by three rapid injection doses or by continuous intravenous infusion over the ensuing 36 hours , providing an equivalent total dose . Echocardiograms and transcranial color flow mapping of the MCA flow velocity were measured at baseline and serially following initiation of therapy in both groups . Effects on cerebral blood flow velocity are presented . RESULTS Eighteen infants [ rapid injection-1.2 + /- 0.3 kg ( n = 9 ) and continuous-1.1 + /- 0.2 kg ( n = 9 ) ] were studied . In the rapid injection treated infants decreased flow velocity in the MCA as manifested by abrupt , significant decreases in systolic ( to 70 + /- 8 % baseline ) and diastolic ( to 65 + /- 13 % baseline ) flow velocity and area under the curve ( to 60 + /- 10 % of baseline ) were evident by 4 minutes and progressed to 30 minutes after treatment initiation . These changes were not observed in the group treated with continuous indomethacin . Both therapeutic modalities were equally successful in closing the ductus , although the numbers are too small to definitively determine therapeutic efficacy . CONCLUSIONS Slow , continuous infusion eliminated the decrease in cerebral flow velocity and appears to be effective in closing the PDA The incidence of persistent patency of the ductus arteriosus beyond the third day of life was prospect ively determined in 100 preterm infants with birthweights of 2,000 gm or less and 50 infants with birthweights of 2,001 to 2,500 gm . The overall incidence was 21 % and was inversely related to increasing gestational age and birthweight . The data suggest that immaturity is the major determinant of the persistent patency of the ductus arteriosus . Spontaneous delayed closure of the ductus occurred in 79 % of patients that survived the immediate neonatal period . There was a high degree of association between the presence of a patent ductus arteriosus ( PDA ) and respiratory distress syndrome ( RDS ) . Eight infants with severe RDS and PDA developed heart failure and four required surgical ligation of the ductus . None of the infants with birthweights greater than 2,000 gm who had PDA developed heart failure or required surgical ligation of the ductus arteriosus Near infrared spectroscopy was used to investigate the effects of intravenously administered indomethacin ( 0.1 - 0.2 mg/kg ) on cerebral haemodynamics and oxygen delivery in 13 very preterm infants treated for patent ductus arteriosus . 7 infants received indomethacin by rapid injection ( 30 s ) and 6 by slow infusion ( 20 - 30 min ) . In all the infants cerebral blood flow , oxygen delivery , blood volume , and the reactivity of blood volume to changes in arterial carbon dioxide tension fell sharply after indomethacin . There were no differences in the effects of rapid and slow infusion . These falls in cerebral oxygen delivery and the disruption of cerebrovascular control might compromise cellular oxygen availability , particularly in regions of the brain where the arterial supply is precarious . Care should be taken to ensure that oxygen delivery is optimum before the administration of indomethacin to preterm infants OBJECTIVE To evaluate the effect of intravenous ibuprofen and indomethacin for treatment of patent ductus arteriosus ( PDA ) on mesenteric and renal blood flow velocity in preterm infants . STUDY DESIGN Seventeen mechanically ventilated preterm infants ( <33 weeks ' gestation ) with PDA received either 0.2 mg/kg indomethacin ( n = 8) or 10 mg/kg ibuprofen ( n = 9 ) , infused over 15 minutes . Mesenteric and renal blood flow velocity were measured by using Doppler ultrasonography . RESULTS Indomethacin caused a significant reduction in mesenteric and renal blood flow velocity 30 minutes after drug administration ; mesenteric and renal blood flow velocity did not return to the pretreatment values by 120 minutes . Ibuprofen did not alter blood flow 30 minutes after treatment , and blood flow increased 120 minutes after treatment . Mesenteric and renal blood flow velocity changes were significantly different between the 2 treatment groups . CONCLUSIONS Compared with indomethacin , ibuprofen did not significantly reduce mesenteric and renal blood flow velocity Among 3559 newborn infants with birth weight less than 1750 gm , 421 developing a hemodynamically significant patent ductus arteriosus were entered into a r and omized trial to evaluate the role of indomethacin in the management of PDA . Indomethacin given concurrently with usual medical therapy at the time of diagnosis result ed in ductal closure in 79 % , versus 35 % with placebo ( P less than 0.001 ) . Indomethacin as backup to usual medical treatment result ed in similar closure rates . To assess overall effects through hospital discharge , three management strategies were compared . Although mortality did not differ significantly , infants given indomethacin only if usual therapy failed ( strategy 2 ) had a lower incidence of bleeding than those to whom indomethacin was given with initial medical therapy ( strategy 1 ) and lower rates of pneumothorax and retrolental fibroplasia than those to whom no indomethacin was administered , with surgery the only backup to medical therapy ( strategy 3 ) . Thus the administration of indomethacin only when medical treatment fails appears to be the preferable approach for the management of symptomatic PDA in premature infants |
12,917 | 27,143,007 | Our results contradict the findings of ecological studies which indicated a strong correlation between the decreasing number of psychiatric beds and an increasing number of people with mental health problems who were homeless or in prison | BACKGROUND Reports linking the deinstitutionalisation of psychiatric care with homelessness and imprisonment have been published widely .
AIMS To identify cohort studies that followed up or traced back long-term psychiatric hospital residents who had been discharged as a consequence of deinstitutionalisation . | Background : With the psychiatric deinstitutionalization movement in its fourth decade , questions are being raised concerning its relevance for long-stay in patients with severe disabilities and the risk that those discharged into the community may be ab and oned . Methods A r and om sample taken in 1989 of long-stay in patients at Louis-H Lafontaine Hospital made it possible to examine 96 pairs of patients . Each pair included 1 patient discharged between 1989 and 1998 and 1 patient hospitalized . Pairs were matched for sex , age , length of stay , and level of psychiatric care in 1989 . Patients and staff were interviewed using st and ardized question naires , and case notes were review ed to assess symptoms , daily living skills , residential status , quality of residential setting , and clinical and social problems and needs . Results The investigation revealed that discharged patients moved to highly supervised setting s , which included professionally supervised group homes , supervised hostels , and foster families . About 20 % went to nursing homes owing to loss of autonomy from physical disorders . Only 4 discharged patients were lost to follow-up , of whom 2 were probable vagrants . Both those discharged and those remaining as in patients presented with major clinical problems and daily living skill deficits . The care needs of discharged patients were generally met , and placement in the community was considered appropriate . Of those who had remained hospitalized , over one-half could be moved to supervised setting s immediately , or after 1 to 2 years ' preparation in a discharge unit , while 13 % could be moved to nursing homes . Over 25 % required intensive , individualized rehabilitation treatment targeting engagement , psychotic symptoms , withdrawal , and dangerous and socially embarrassing behaviours . Conclusion Deinstitutionalization in the largest Canadian psychiatric hospital did not lead to patient ab and onment in the community Background Homelessness and mental illness have a strong association with public disorder and criminality . Experimental evidence indicates that Housing First ( HF ) increases housing stability and perceived choice among those experiencing chronic homelessness and mental disorders . HF is also associated with lower residential costs than common alternative approaches . Few studies have examined the effect of HF on criminal behavior . Methods Individuals meeting criteria for homelessness and a current mental disorder were r and omized to one of three conditions treatment as usual ( reference ) ; scattered site HF ; and congregate HF . Administrative data concerning justice system events were linked in order to study prior histories of offending and to test the relationship between housing status and offending following r and omization for up to two years . Results The majority of the sample ( 67 % ) was involved with the justice system , with a mean of 8.07 convictions per person in the ten years prior to recruitment . The most common category of crime was “ property offences ” ( mean = 4.09 ) . Following r and omization , the scattered site HF condition was associated with significantly lower numbers of sentences than treatment as usual ( Adjusted IRR = 0.29 ; 95 % CI 0.12–0.72 ) . Congregate HF was associated with a marginally significant reduction in sentences compared to treatment as usual ( Adjusted IRR = 0.55 ; 95 % CI : 0.26–1.14 ) . Conclusions This study is the first r and omized controlled trial to demonstrate benefits of HF among a homeless sample with mental illness in the domain of public safety and crime . Our sample was frequently involved with the justice system , with great personal and societal costs . Further implementation of HF is strongly indicated , particularly in the scattered site format . Research examining interdependencies between housing , health , and the justice system is indicated . Trial registration IS RCT OBJECTIVE In Upper Austria , a total of 409 long-stay patients were discharged to various residential facilities between 1995 and 2000 . This paper describes psychopathology and sociodemographic characteristics . METHODS A r and om sample of 116 former long-stay patients were followed for an average 42.9 months after discharge . RESULTS Patients had spent an average 19.3 years in psychiatric wards . 47 patients ( 40.5 % ) were placed in nursing homes , 16 patients ( 13.8 % ) in old-age homes , 32 patients ( 27.6 % ) in other institutions and only 15 patients ( 12.9 % ) in group homes , and 6 patients ( 5.2 % ) with families . ICD-10 diagnosis was schizophrenia in 56 patients ( 48.3 % ) and mental retardation in 33 patients ( 28.4 % ) . Level of social and functional disabilities was high . CONCLUSIONS Most long-stay patients were able to live outside psychiatric hospitals , but institutional care still plays an essential role BACKGROUND Long-stay patients with learning disabilities ( n = 214 ) were assessed in hospital and 12 and 24 months after discharge in order to examine the effects of relocation . METHOD Each resident acted as his/her own control in a prospect i ve repeated- measures design . Skills and behavioural problems were assessed by keyworkers . Self-perceived quality of life was obtained during interviews with research ers who also completed an environmental checklist of the residents ' accommodation . RESULTS There was little or no change in people 's low pre-discharge skill levels . Certain aspects of problem behaviour improved after 12 months , although socially unacceptable behaviour increased slightly . People were less depressed ( P < or = 0.01 ) 12 months after discharge ( N = 119 ) and were more satisfied ( P < or = 0.05 ) with their new ' homes ' ( n = 108 ) . There were few changes in the pattern of activities or the social networks of people 12 months later . Little or no further change in outcomes was reported 24 months after discharge . CONCLUSIONS The implementation of the deinstitutionalisation policy in Northern Irel and has been limited by the predominance of residential and nursing homes and the lack of ' ordinary ' accommodation . There is a need for purchasers and providers to give more attention to ways in which the principles of normalisation could be incorporated in the process of contracting and delivering services This paper review s briefly the history of mental health de population in Canada over the past 30 years . The term “ deinstitutionalization ” is often used but is unsatisfactory . Using an exploratory , qualitative , method ological approach , data were collected on the problems encountered by a disproportionate , stratified r and om sample of 139 formerly institutionalized patients living in various geographical locales in Eastern Canada . Adopting a symbolic interactionist theoretical approach , this study , in an effort to fill a neglect in the literature , attempted to discover what the everyday world(s ) of Canadian ex-mental patients was really like . Problems encountered related to stigma , poor housing , lack of back living skills , poverty , unemployment and aftercare . Quotations from patients are provided to illustrate such themes . The findings are discussed OBJECTIVES The purpose of this study was to evaluate effects associated with moving patients from hospital to community-based setting s , to compare persons who left the hospital with those who remained in the hospital , and to address the question of whether discharge reverses institutionalism in a sample of elderly long-stay psychiatric in patients . METHODS The hypotheses were that , compared with the control group of patients who stayed in the hospital , those who left would have significantly better mental states , social functioning , and social networks at follow-up ; that community setting s would provide a significantly better quality of environment than the hospital ; and that discharged patients would express a preference for community care after discharge from the hospital . The study was a prospect i ve nonr and omized controlled trial at Cane Hill , Friern , and Claybury Hospitals in Engl and . Sixty long-term patients with schizophrenia who were discharged to community care were compared over time with matched controls ( N=131 ) . RESULTS No overall differences were detected in the pattern or severity of symptoms between patients who were discharged from the hospital and those who were not , and no significant changes over time were noted . Significant improvements in social networks , patients ' preference for community setting s , and quality of clinical environment were noted . CONCLUSIONS These results give qualified support for moving long-stay psychiatric patients from hospital to community setting BACKGROUND The effects of hospital-based rehabilitation including weekly supportive psychodynamic therapy compared with specialized assertive intervention and st and ard treatment has not previously been investigated in first-episode psychosis . The aim of the study was to examine long-term effect on use of institutional care of different intensive interventions for patients with first-episode schizophrenia spectrum disorder on use of psychiatric bed days and days in supported housing . METHOD A total of 94 severely ill patients with first-episode schizophrenia spectrum disorders were included in a special part of the Copenhagen OPUS trial and r and omized to either the specialized assertive intervention program ( OPUS ) , st and ard treatment or hospital-based rehabilitation . RESULTS It was a stable pattern that patients r and omized to hospital-based rehabilitation spent more days in psychiatric wards and in supported housing throughout the 5-year follow-up period compared with the two other groups . Patients in OPUS treatment spent significantly fewer days in psychiatric wards and supported housing in the first 3 years compared with patients in hospital-based rehabilitation . Due to attrition and small sample size , differences in level of psychotic and negative symptoms at 5-year follow-up could not be evaluated . CONCLUSIONS The study indicates that hospital-based rehabilitation together with weekly supportive psychodynamic therapy was associated with a continued increased use of psychiatric bed days and days in supported housing . The data can not justify using hospital-based rehabilitation in first-episode psychosis Background : This study examines the psychosocial outcomes of women discharged from the Vlore Psychiatric Hospital in Albania . Methods : The study was design ed as a controlled , not r and omized , follow-up study . It included 16 women diagnosed with psychosis who were discharged from a psychiatric hospital to live in group homes in the community . The control group included 20 women diagnosed with psychosis who lived at the psychiatric hospital while awaiting discharge . All subjects were assessed twice using the HoNOS-Rome tool , at the start of the study ( T0 ) and 12 months later ( T1 ) . Results : Both groups showed an improvement in the HoNOS total score between T0 and T1 ( p < .001 ) . This improvement was significantly larger in the Home group compared to the Hospital group ( p = .014 ) . An item-level analysis indicated a significantly greater improvement in the Home group on items 11 ( autonomy ) , 12 ( work ) , 16 ( family ) and 18 ( goals ) . Conclusions : Projects for social inclusion of people suffering from psychosis must design living spaces that offer viable alternatives to psychiatric hospitals . This study also documents the efforts in the Vlore region of Albania to follow European st and ards of mental health care |
12,918 | 12,698,183 | General availability of full individual patient data is a necessary step forward and would overcome the majority of problems encountered , including poorly reported summary statistics and variability in cutoff level , outcome assessed and adjustment factors used . | Prognostic markers help to stratify patients for treatment by identifying patients with different risks of outcome ( e.g. recurrence of disease ) , and are important tools in the management of cancer and many other diseases .
Systematic review and meta-analytical approaches to identifying the most valuable prognostic markers are needed because ( sometimes conflicting ) evidence relating to markers is often published across a number of studies . | Summary Prognostic models that predict the clinical course of a breast cancer patient are important in oncology . We propose an approach to constructing such models based on fractional polynomials in which useful transformations of the continuous factors are determined . The idea may be applied with all types of regression model , including Cox regression , the method of choice for survival-time data . We analyse a prospect i ve study of node-positive breast cancer . Seven st and ard prognostic factors – age , menopausal status , tumour size , tumour grade , number of positive lymph nodes , progesterone and oestrogen receptor concentrations – were investigated in 686 patients , of whom 299 had an event for recurrence-free survival and 171 died . We determine a final model with transformations of prognostic factors and compare it with the more traditional approaches using categorized variables or assuming a straight line relationship . We conclude that analysis using fractional polynomials can extract important prognostic information which the traditional approaches may miss |
12,919 | 18,713,924 | RESULTS : Continuous paravertebral block was as effective as thoracic epidural analgesia with local anesthetic ( LA ) but was associated with a reduced incidence of hypotension .
Paravertebral block reduced the incidence of pulmonary complications compared with systemic analgesia , whereas thoracic epidural analgesia did not .
Thoracic epidural analgesia was superior to intrathecal and intercostal techniques , although these were superior to systemic analgesia ; interpleural analgesia was inadequate .
: Either thoracic epidural analgesia with LA plus opioid or continuous paravertebral block with LA can be recommended . | BACKGROUND : Thoracotomy induces severe postoperative pain and impairment of pulmonary function , and therefore regional analgesia has been intensively studied in this procedure .
Thoracic epidural analgesia is commonly considered the “ gold st and ard ” in this setting ; however , evaluation of the evidence is needed to assess the comparative benefits of alternative techniques , guide clinical practice and identify areas requiring further research . | Severe postoperative pain , which may persist for up to 3 days and may lead to postoperative complications , due to the patient 's inability to breathe deeply and cough , is frequently experienced in the area of the incision and chest tubes by thoracotomy patients . Eighteen patients undergoing routine thoracotomies were tested preoperatively for arterial blood gases and pulmonary function and given chest x – rays . Anesthesia consisted of thiopental , succinylcholine , N2O , enflurane , and pancuronium . Before incision closure , 6 intercostal spaces were injected by the surgeon with 3 ml of a r and omly determined drug mixture . Patients received either bupivacaine and saline solution , bupivacaine and LMW dextran 40 , or saline and LMW dextran 40 . Arterial blood gases , pulmonary function , chest x-rays , narcotic dosage , sensory level , and subjective responses were evaluated for 3 days postoperatively . Results demonstrate that intercostal nerve blocks can markedly reduce postoperative pain and improve pulmonary function in such patients . Significant differences from controls were seen in Paoz , Paces , vital capacity , forced expiratory flow rates , analgesic requirements , and patient comfort . The duration of the block with bupivacaine and saline was less than 12 hours , while the mean duration of the block with bupivacaine and dextran 40 was 36 hours Twenty patients scheduled for lateral thoracotomy were r and omly allocated to receive either epidural morphine at regular intervals or subcutaneous nicomorphine on dem and for postoperative pain relief . The daily dose of opiate administered was greater in the group receiving subcutaneous nicomorphine than in the epidural group although four patients in the latter needed additional subcutaneous injections of opiate . During the first three days of the postoperative course , a profound decrease of the forced vital capacity ( FVC ) , the forced expiratory volume in one second ( FEV1 ) , peak expiratory flow rate ( PEF ) and the arterial oxygen tension ( PaO2 ) was found in both groups , whereas the visual analogue pain score showed a marked increase , and the arterial pH and carbon dioxide tension ( PaCO2 ) remained unchanged . No significant difference could be demonstrated between the group;s . The conclusion is that epidural morphine may produce sufficient pain relief after thoracotomy , but compared with conventional pain treatment the benefits are limited Administration of large doses of fentanyl is a popular method to provide postoperative analgesia after thoracotomy . It is however unclear whether epidural lumbar ( L ) or epidural thoracic ( T ) administration of fentanyl confers any major advantage over intravenous ( iv ) infusion . Using a r and omized prospect i ve study design , we compared the potential benefits of L , T , and iv fentanyl administration after thoracotomy in 50 patients . Epidural catheters were not injected during surgery . Postoperatively a fentanyl infusion ( 5 micrograms/ml ) was started at 1 microgram.kg-1.h-1 after a bolus of 1 microgram/kg and adjusted to maintain a score < or = 30/100 at rest using a visual analog scale ( VAS ) for pain . Data were prospect ively collected before surgery , at fixed intervals during the 48 h of fentanyl infusions , and the day of discharge . There was no difference between the groups in overall quality of analgesia at rest and after coughing , quantity of fentanyl delivered ( L = 1.15 + /- 0.38 , T = 1.22 + /- 0.23 , iv = 1.27 + /- 0.3 micrograms.kg-1.h-1 ) , incidence of pruritus needing treatment ( L = 2 , T = 1 , iv = 0 patients ) , need to decrease fentanyl infusion rate because of side effects ( L = 2 , T = 2 , iv = 4 patients ) , importance of pulmonary infiltrates , or arterial blood gas values . One patient ( L group ) needed naloxone ( 0.04 mg iv ) . Intravenous patients were more frequently nauseated ( P = .009 ) and needed boluses of fentanyl more often ( L = 3 + /- 9 , iv = 6 + /- 12 , T = 4 + /- 8 ; P = .04 ) . ( ABSTRACT TRUNCATED AT 250 WORDS In this clinical , r and omized , prospect i ve study , we compared the effects of three different analgesia techniques ( thoracic epidural analgesia [ TEA ] with and without preoperative initiation and IV patient-controlled analgesia [ IV-PCA ] ) on postthoracotomy pain in 69 patients . In two groups , a thoracic epidural catheter was inserted preoperatively . Group Pre-TEA had bupivacaine and morphine solution preoperatively and intraoperatively . Postoperative analgesia was maintained with epidural PCA with a similar solution . Group Post-TEA , with no intraoperative medication , had the same postoperative analgesia as Group Pre-TEA plus the bolus dose . Group IV-PCA received only IV-PCA with morphine for postoperative analgesia . Pain was evaluated every 4 h during the first 48 h at rest , cough , and movement . Pre-TEA was associated with decreased pain compared with the other groups . Six months later , the patients were asked about their pain . The incidence and the intensity of pain were most frequent in Group IV-PCA ( 78 % ) and were the least in Group Pre-TEA ( 45 % ) ( Group Pre-TEA versus Group IV-PCA , P = 0.0233 ; Group Pre-TEA versus Group IV-PCA , P = 0.014 ) . Patients having pain on the second postoperative day had 83 % chronic pain . TEA with preoperative initiation is a preferable method in preventing acute and long-term thoracotomy pain Four different pain treatments ( single intercostal block with bupivacaine , repeated intercostal block , epidural morphine and epidural bupivacaine infusions ) were compared in 39 patients subjected to lung surgery under general anaesthesia . The patients ' own estimate of the postoperative pain was not significantly different between the groups , but the epidurally treated patients required fewer doses of supplementary analgesic than those given just a single dose of intercostal bupivacaine . Bupivacaine levels in blood were below the toxic range in all groups . The concentration of antidiuretic hormone in blood was increased early during the operation , and had only partly returned to normal on the first postoperative morning . Growth hormone in plasma was increased only at the end of the operation . Catecholamine levels in blood increased gradually , reaching their peak postoperatively . There were only slight differences between the groups in these posterior and anterior pituitary and sympatho‐adrenal responses to surgical stress . Thus , neither repeated intercostal blockade nor epidural administration of morphine or bupivacaine could prevent the endocrine responses to thoracic surgery , in spite of significant , albeit incomplete , pain relief . This was probably caused in part by residual pain , and also by poor access of the extradural medications to the autonomic afferent pathways mediating nociceptive signals from thoracic organs and tissues This study was undertaken to evaluate the effectiveness of 0.5 % bupivacaine ( 360 mg/day ) as a continuous infusion through an indwelling intercostal catheter inserted intraoperatively in the management of pain after thoracotomy . Eighty-six patients were r and omized into three groups : group 1 = intercostal bupivacaine , group 2 = intercostal saline solution , and group 3 = fixed-schedule intramuscular buprenorphine . Supplementary buprenorphine was given as required . Pain and pulmonary function were assessed throughout the first 5 days after operation . Pain score was lower in group 1 than in group 2 for the first 8 hours after operation ( p < 0.02 ) . During the first 3 postoperative days , mean postoperative pain scores of 5 or more were recorded in 9 % of group 1 patients versus 40 % of group 2 patients ( p < 0.05 ) and 13 % of group 3 patients ( not significant ) . Total doses of buprenorphine were lower in groups 1 and 2 than in group 3 ( p < 0.001 ) . No between-group differences in pulmonary function were observed . Respiratory complications occurred in no patients in groups 1 and 3 versus 5 in group 2 ( p < 0.05 ) . Continuous intercostal bupivacaine provided similar early pain control as compared with fixed-schedule narcotics but induced better analgesia with fewer complications than on-dem and narcotics alone ( group 2 ) The purpose of this study was to compare meperidine to meperidine with bupivacaine when used for patient-controlled epidural analgesia ( PCEA ) after thoracotomy . For 3 days after thoracotomy patients received thoracic PCEA with meperidine 0.1 % plain or with added bupivacaine 0.1 % or 0.01 % . No background infusion was used . All patients received indomethacin postoperatively for the duration of the study . Patients were assessed with respect to meperidine consumption , analgesia , and side effects . Sixty-six patients participated . Patients in all three groups obtained effective analgesia with median meperidine consumption of 5 - 6 mg/h . There were no significant differences between groups in meperidine consumption or pain scores at rest or with coughing . The addition of bupivacaine 0.1 % reduced the incidence of pruritus ( P = 0.036 ) , but 5 of 23 patients in this group were withdrawn from the study because of significant hypotension , oliguria , and /or motor or sensory block ( P = 0.006 ) . We conclude that the addition of bupivacaine 0.1 % or 0.01 % to thoracic PCEA meperidine 0.1 % does not affect meperidine requirements or analgesia after thoracotomy . The addition of bupivacaine 0.1 % may reduce pruritus , but is associated with signs of excessive sensory , motor , or autonomic blockade in a significant number of patients . ( Anesth Analg 1996;83:81 - 6 OBJECTIVE Long-term pain is a common sequela of thoracotomy , occurring in approximately 50 % of patients 2 years after thoracic surgery . Despite this alarming statistic , little is known about the factors responsible for the transition of acute to chronic pain . The aim of the present study is to identify predictors of long-term post-thoracotomy pain . DESIGN Follow-up was for 1.5 years for patients who had participated in a prospect i ve , r and omized , controlled trial of preemptive , multimodal analgesia . SETTING Subjects were recruited from a tertiary care center . PATIENTS Thirty patients who had undergone lateral thoracotomy were followed up by telephone , administered a structured interview , and classified according to long-term pain status . MAIN OUTCOME MEASURES Present pain status was measured by a verbal rating scale ( VAS ) . Measures obtained within the first 48 h after surgery were compared between patients with and without pain 1.5 years later . These include VAS pain scores at rest and after movement , McGill Pain Question naire data , patient-controlled morphine consumption ( mg ) , and pain thresholds to pressure applied to a rib contralateral to the thoracotomy incision . RESULTS Fifty-two percent of patients reported long-term pain . Early postoperative pain was the only factor that significantly predicted long-term pain . Pain intensity 24 h after surgery , at rest , and after movement was significantly greater among patients who developed long-term pain compared with pain-free patients . A significant predictive relationship was also found at 24 and 48 h using the McGill Pain Question naire . Cumulative morphine was comparable for the two groups . Pain thresholds to pressure applied to a rib contralateral to the incision did not differ significantly between the groups . CONCLUSION Aggressive management of early postoperative pain may reduce the likelihood of long-term post-thoracotomy pain Twenty‐five ASA 1 or 2 patients undergoing thoracotomy were entered into a prospect i ve , r and omised , double‐blind study comparing thoracic epidural fentanyl alone and thoracic epidural fentanyl combined with 0.2 % bupivacaine . Pain relief , pulmonary function and cardiovascular stability were assessed . Pain relief was superior in the bupivacaine series ( p < 0.05 ) during the first day after operation and this was accompanied by better oxygenation ( p < 0.05 ) ; the difference did not persist into the second day . Forced expiratory variables were reduced in both series to 50–60 % of the values before operation throughout the study ( p < 0.05 ) and differences did not occur between the groups . The incidence of side effects attributable to epidural fentanyl was high , but hypotension did not occur . Small doses of bupivacaine administered together with fentanyl into the thoracic epidural space improve analgesia without causing hypotension The effects of diamorphine hydrochloride 0.1 mg/kg , given either extradurally or intramuscularly for postoperative analgesia were compared in two r and omised double‐blind studies involving 39 patients undergoing thoracotomy and major gynaecological surgery . Assessment s were made at fixed intervals after the administration of diamorphine and consisted of the measurement of pain or analgesic effect . Segmental , sympathetic and any adverse effects were sought . There was no significant difference in the quality of analgesia between the two groups in either trial . Extradural diamorphine provided safe and effective analgesia of rapid onset , with no specific undesirable side‐effects . In both studies , analgesia was more prolonged following extradural administration . The relative proportion of spinal binding may be increased after extradural administration and this may be reflected in the prolonged analgesia observed We studied 20 patients undergoing thoracotomy , in a double-blind , placebo-controlled crossover trial of intercostal bupivacaine . Bupivacaine 0.25 % was infused at 5 ml h-1 through each of two catheters placed in the intercostal space at operation . Mean ( 95 % confidence limits ) 24-h requirements for morphine from a patient-controlled analgesia device were 29 ( 22 - 37 ) mg during bupivacaine infusion and 44 ( 32 - 57 ) mg during saline infusion ( P = 0.04 ) . Patients also recorded significantly smaller visual analogue scores for pain during bupivacaine infusion . There were no adverse effects related to the intercostal infusion of bupivacaine . We conclude that bupivacaine , infused through catheters placed during thoracotomy in the adjacent intercostal spaces , is a useful adjunct to systemic opioid analgesia BACKGROUND The present study was design ed to evaluate the effectiveness of intrapleural 0.25 % bupivacaine delivered by intermittent infusions for post-thoracotomy pain relief . METHODS Forty patients undergoing elective lobectomy were r and omly , but equally , placed into two groups . An intrapleural catheter was inserted under direct vision during surgery . Group I received intrapleural 40 mL of 0.25 % bupivacaine , group II was administered 40 mL of saline solution as a control group . Diclofenac sodium was administered as an additional analgesic , if required . Postoperative pain was evaluated using a visual analog scale ( VAS ) , and Prince Henry pain scale . Arterial oxygen saturation , heart rate , and systemic arterial pressures were monitored . All observations were recorded 5 , 10 , 15 , 20 , 25 , and 30 minutes after the injection , and thereafter at hourly intervals through the postoperative 24 hours . RESULTS The mean analgesia times were 5 hours and 2 hours in group I and group II , respectively . Therefore , bupivacaine administrations were repeated every 6 hours in group I , and saline with additional analgesic were administered every 4 hours in group II . The heart rate and arterial pressures did not show a significant difference . While the additional analgesic requirement was 180 + /- 10 mg/d in group II , there was no need for additional analgesic administration in the group I patients . Arterial oxygen was significantly higher in group I than in group II . Arterial carbon dioxide tension of group II was significantly higher than that of group I. While the postoperative atelectasis and pneumonia developed in four patients and one , respectively , in group II , no such complication was observed in group I. CONCLUSIONS The easy placement of an intrapleural catheter and better pain relief observed in the present study suggest that intermittent pleural infusion of 0.25 % bupivacaine has proven to be a safe and effective method for relief of post-thoracotomy pain This study examined the beneficial effects and potential systemic toxicity from continuous intercostal nerve block by repeated bolus injections of bupivacaine . In this double-blind , r and omized study , 20 post-thoracotomy patients were assigned to receive four doses of either : 20 ml 0.5 % bupivacaine with epinephrine 5 μg · ml−1 ( bupivacaine group , n = 10 ) , or 20 ml preservative-free saline ( placebo group , n = 10 ) through two indwelling intercostal catheters every six hours . Patients receiving intercostal bupivacaine injections had greater decreases in visual analogue pain scores ( VAS ) ( P < 0.05 ) and lower 24 hr morphine requirements , 16.6 ±4.6 mg vs 35.8 ±7.2 mg , than patients in the placebo group ( P < 0.05 ) . Higher post-injection values of forced expiratory volume in one second , forced vital capacity and peaked expiratory flow rate were also observed in the bupivacaine group ( P < 0.01 ) . Repeated intercostal bupivacaine administration did lead to systemic accumulation , but the peak bupivacaine level after 400 mg was low at 1.2 ±0.2 μg · ml−1 . Thus , the technique of continuous intercostal nerve block described in this study is an effective treatment for the control of post-thoracotomy pain . RésuméCette étude examine les effets bénéfiques et la toxicité systémique potentielle d’un bloc nerveux intercostal continu par des injections répétées de bupivacaïne . Dans cette étude r and omisée chaque six heures à double insu , 20 patients posl-thoracotomie ont été divisés afin de recevoir quatre doses de soit : 20 ml 0,5 % de bupivacaïne avec épinéphrine 5 μg · ml−1 ( groupe bupivacaïne , n = 10 ) , ou 20 ml de soluté physiologique sans préservatif ( groupe placébo , n = 10 ) via un cathéter intercostal chaque six heures . Les patients recevant des injections de bupivacaïne intercostal ont démontré une plus gr and e diminution dans le test du « Visual analogue pain scores ( VAS ) ( P < 0.05 ) » et ont requis en 24 heures moins de morphine , 16,6 ±4,6 mg vs 35,8 ±7,2 mg que les patients du groupe placebo ( P < 0.05 ) . Les valeurs post-injection plus élevées étaient notées dans le FEV1 , la capacité vitale forcée et le flot expiratoire maximal pour le groupe bupivacaïne ( P < 0.01 ) . L’administration répétée de bupivacaïne intercostale a amené une accumulation systémique mais le niveau maximal de bupivacaïne après 400 mg était bas à 1,2 ±0,2 μg · ml−1 . Ainsi , la technique du bloc nerveux intercostal continu décrite dans cette étude fut un moyen thérapeutique efficace pour le contrôle de la douleur post-thoracotomie There is still controversy concerning the beneficial aspects of ' dynamic analgesia ' ( i.e. pain while coughing or moving ) on the reduction of postoperative atelectasis . In this study , we tested the hypothesis that thoracic epidural analgesia ( TEA ) prevents these abnormalities as opposed to multimodal analgesia with i.v . patient controlled analgesia ( i.v . PCA ) after thoracotomy . Fifty-four patients undergoing thoracotomy ( lung cancer ) were r and omly assigned to one of the two groups . Clinical respiratory characteristics , arterial blood gas , and pulmonary function tests ( forced vital capacity and forced expiratory volume in 1 s ) were obtained before surgery and on the next 3 postoperative days . Atelectasis was compared between the two groups by performing computed tomography ( CT ) scan of the chest at day 3 . Postoperative respiratory function and arterial blood gas values were reduced compared with preoperative values ( mean ( SD ) FEV1 day 0 : 1.1 ( 0.3 ) litre ; 1.3 ( 0.4 ) litre ) but there was no significant difference between groups at any time . PCA and TEA provided a good level of analgesia at rest ( VAS day 0 : 21 ( 15/100 ) ; 8 ( 9/100 ) ) , but TEA was more effective for analgesia during mobilization ( VAS day 0 : 52 ( 3/100 ) ; 25 ( 17/100 ) ) . CT scans revealed comparable amounts of atelectasis ( expressed as a percentage of total lung volume ) in the TEA ( 7.1 (2.8)% ) and in the i.v . PCA group ( 6.71 (3.2)% ) . There was no statistical difference in the number of patients presenting with at least one atelectasis of various types ( lamellar , plate , segmental , lobar ) A r and omised double‐blind clinical trial was conducted on 106 patients scheduled for pulmonary resection . Patients received an epidural infusion containing 0.1 % , 0.2 % bupivacaine or saline in combination with fentanyl 10 μg.ml −1 . Adequacy of analgesia was assessed at rest and during movement over 24 h. Analgesic efficacy was assessed using visual analogue scores and an observer/verbal ranking scale . Pain scores were higher in the fentanyl‐only group at the 2 h assessment ( p < 0.05 ) . Otherwise , there were no between‐group differences in pain scores or in the total amounts of epidural solution used . All patients received continuous haemodynamic monitoring . There were no between‐group differences in the number of episodes of hypotension or in the number of interventions for hypotension . However , the use of intra‐operative vasopressor and the incidence of temporary neurological complications was higher in the 0.2 % bupivacaine group ( p < 0.05 ) . We conclude that , in the early postoperative period , the addition of bupivacaine 0.1 % improves fentanyl epidural analgesia in patients undergoing lung resection and is not associated with the disadvantages seen with the addition of bupivacaine 0.2 % BACKGROUND Epidural analgesia is widely employed as a means to control postthoracotomy pain , but is sometimes inadequate . The purpose of this study is to evaluate the effectiveness of intraoperative , temporary , intercostal nerve blockade in addition to epidural analgesia for control of postthoracotomy pain . METHODS Forty patients undergoing elective lobectomy through antero-axillary thoracotomy were r and omized to receive epidural analgesia only ( group A , n = 20 ) or epidural analgesia plus temporary , intraoperative intercostal nerve blockade using 0.25 % bupivacaine ( group B , n = 20 ) . Postoperative pain was assessed using a subjective analogue visual scale , and with the Prince Henry pain scale . Food intake and nonsteroidal analgesic consumption were also investigated . Serum ACTH and cortisol in each group were measured before and after the operation . RESULTS The analogue visual scale scores were significantly higher in group A than group B ( p < 0.001 ) , and were significantly higher on the day of operation and postoperative days 1 , 2 , and 3 ( p < 0.001 , p < 0.005 , p < 0.005 , p < 0.05 , respectively ) . Prince Henry pain scale scores were significantly higher on the day of operation and postoperative day 1 ( p < 0.05 , p < 0.005 , respectively ) . Food intake was significantly lower in group A than in group B ( p < 0.05 ) , and nonsteroidal analgesic consumption was not significantly different between groups . There was no significant difference between group A and group B in serum ACTH or in cortisol levels . CONCLUSIONS Additional intraoperative intercostal nerve blockade provides an additive benefit for postthoracotomy pain relief , especially early after operation 54 patients who had posterolateral thoracotomy were prospect ively studied to compare the efficacy of intrapleural bupivacaine with that of bupivacaine intercostal block and cryofreezing . Patients were r and omized into three groups . The intrapleural catheter group included 16 patients who had intermittent intrapleural instillation of 20 ml of 0.25 % bupivacaine for forty-eight hours postoperatively . The second group included sixteen patients who were given perioperative bupivacaine intercostal block . The third group included fifteen patients treated by cryofreezing of the intercostal nerves . Visual analogue four-hourly pain score was compared between the three groups during the first forty-eight hours postoperatively . The analgesic requirements during the first postoperative week were also assessed . There was no significant difference between the three groups in the average pain score ( 3.61 + /- 1.37 , 3.54 + /- 1.15 , and 3.33 + /- 1.47 respectively ) . During the first forty-eight hours postoperatively , the percentage of patients who required papaveretum in the intrapleural catheter group ( 56.3 % ) was significantly less than that in the other two groups ( both 100 % ) . The average papaveretum requirement ( mg per patient ) in the intrapleural catheter group ( 27.33 + /- 25.27 ) was significantly less than that in the second group ( 52.66 + /- 26.85 ) but the difference was not statistically significant from that in the third group ( 37.66 + /- 20.95 ) . No complications related to the use of the intrapleural catheter or to bupivacaine toxicity were encountered . In conclusion , the technique of intermittent intrapleural bupivacaine is safe and comparable in efficacy to bupivacaine intercostal block and cryofreezing . Narcotic requirements may be reduced when this technique is used The effect of continuous epidural analgesia with bupivacaine 0.125 % and sufentanil 0.83 μg·ml−1 on the plasma cortisol concentration and postoperative pain relief was compared with that of intermittent intravenous peroperative and on-dem and intramuscular postoperative analgesia with nicomorphine 0.2 mg·kg−1 . The study was performed on two groups of ten patients for three consecutive days after thoracic surgery . In the epidural group , a better quality of analgesia was found as measured with the Inverse Linear Analgesia Scale ( ILAS ) ( 1 = severe pain , 10 = no pain ) than in the group that received intramuscular analgesia . The mean ILAS scores in the epidural group were : day 1 , 8.1 ( SD , 1.26 ) ; day 2 , 8.3 ( SD , 0.87 ) ; day 3 , 8.6 ( SD , 0.71 ) . The corresponding mean ILAS scores in the systemic group were 7.3 ( SD , 1.38 ) , 7.4 ( SD , 1.16 ) , and 7.6 ( SD , 1.15 ) . There was a significant difference between the ILAS scores for the two groups on all days ( p < 0.01 ) . The mean plasma cortisol concentration was not significantly different between the groups during the period of investigation . In the epidural group , the highest measured mean cortisol concentration of 520.2 ( SD , 266.4 ) nmol·L−1 was on day 2 , whereas that in the systemic group was 738.3 ( SD , 255.1 ) nmol·L−1 on day 1 . The measured mean plasma cortisol concentration was found to exceed normal limits ( 150 - 700 nmol·L−1 ) only in the systemic group and only on day 1 To assess the efficacy of continuous extrapleural intercostal nerve block ( CEINB ) with 0.5 % bupivacaine on postoperative pain , pulmonary function and pulmonary complications , a prospect i ve , r and omised , double blind controlled trial was conducted on comparable patients undergoing lung resections ; n = 21 ( control ) , n = 25 ( bupivacaine ) . The bupivacaine group required less papaveretum in the first 24 h ( P less than 0.01 ) and had lower pain scores over 5 postoperative days ( P less than 0.01 ) . Pulmonary function recovered earlier in the bupivacaine group . Pulmonary complications occurred in 1 patient with normal lung function and 12 patients with obstructive airways disease ( COAD ) : FEV1/FVC less than 70 % . There were no infusion-related complications . CEINB has been shown to be safe and effective in reducing postoperative pain and pulmonary complications . CEINB minimises the loss of lung function after thoracotomy and restores impaired pulmonary mechanics more rapidly The effect of intrapleural bupivacaine in the treatment of post – thoracotomy pain was evaluated . Bupivacaine , 0.5 % 20 ml , with adrenaline ( 5 μg/ml ) was given through an indwelling intrapleural catheter , at 4–h intervals four times daily for 2 days . No pleural suction was applied during and 10 min after each injection . A control group received intramuscular oxycodone on request . A visual analogue scale ( VAS ) , a pain question naire ( PQ ) and registration of the need for supplementary analgesics were used for the assessment of postoperative analgesia . Blood – gas analyses showed elevated Pacoz values in both groups on the day of operation and on the first postoperative day , without differences between the groups . Plasma concentrations of bupivacaine did not reach toxic values , and no symptoms of central nervous toxicity or any other untoward reactions were found during the study period . Clinical ly , there was some pain relief after the intrapleural bupivacaine . The VAS and PQ scores 30 min after bupivacaine instillations diminished to an extent similar to that after oxycodone treatment . The need for analgesics during the day of operation was less in the bupivacaine group than in the control group ( P < 0.001 ) . The number of oxycodone supplementation doses during 48 h postoperatively was , however , not smaller in the bupivacaine group than in the control group To evaluate the effects of continuous extrapleural intercostal nerve block on post-thoracotomy pain and pulmonary complications , a r and omized , double-blind , placebo-controlled study was conducted on 80 patients undergoing elective thoracotomy for pulmonary ( n = 47 ) or oesophageal ( n = 33 ) procedures . In patients who received continuous bupivacaine infusion , the requirement for intramuscular opiate and rectal diclofenac was less , the score on a visual linear analogue pain scale lower and recovery of pulmonary function more rapid than in saline-infused controls . Postoperative pulmonary complications occurred in 35 % of the saline group , but only 10 % of the patients with bupivacaine infusion ( p < 0.01 ) . In patients with chronic obstructive airways disease ( COAD ) , the incidence of postoperative pulmonary complications was 54.5 % in the saline group and only 4.5 % in the bupivacaine group ( p < 0.01 ) . Among the patients without COAD there was no significant intergroup difference in such complications . We conclude that continuous extrapleural intercostal nerve block is effective for post-thoracotomy analgesia and reduces pulmonary complications of thoracotomy in patients with COAD 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 We have undertaken a prospect i ve , r and omized comparison of the superficially similar techniques of interpleural and paravertebral ( extrapleural ) analgesia in 53 patients undergoing posterolateral thoracotomy . Local anaesthetic placed anterior to the superior costotransverse ligament and posterior to the parietal pleura produces a paravertebral block and instilled between the parietal and visceral pleurae produces an interpleural block . Patients received preoperative and postoperative continuous bupivacaine paravertebral blocks in group 1 and interpleural blocks in group 2 . Premedication comprised diclofenac and morphine , and after operation all patients had regular diclofenac and patient-controlled morphine ( PCM ) . Analgesia was assessed by visual analogue pain scores ( VAS ) , PCM requirements , ratio of preoperative to postoperative spirometric values ( PFT ) , rates of postoperative respiratory morbidity ( PORM ) and hospital stay , all recorded by blinded observers . Eight patients were withdrawn and data from 45 patients were analysed . Patient characteristics , surgery , VAS scores and PCM use were similar in both groups . PFT were significantly better ( P = 0.03 - 0.0001 ) in group 1 , and PORM was lower and hospital stay approximately 1 day less in this group . Five patients in group 2 became temporarily confused , probably because of bupivacaine toxicity ( P = 0.02 ) . We conclude that bupivacaine deposited paravertebrally produced greater preservation of lung function and fewer side effects than bupivacaine administered interpleurally Background and Objectives . Thoracotomy is associated with pain and compromised pulmonary function . Intercostal nerve blocks ( INB ) and subarachnoid morphine ( SM ) act on different portions of the pain pathway . Each is effective for post-thoracotomy pain relief . The combination of these two modalities in relieving post-thoracotomy pain and improving postoperative pulmonary function has not been investigated . Methods . In a double-blind study , 20 patients undergoing lateral thoracotomy for lung resection were r and omized to receive 0.5 mg SM preoperatively and INB with bupivacaine ( INB+ ) prior to wound closure or 0.5 mg SM with INB using saline ( INB- ) . Visual analog scale pain scores at rest , with cough , and with movement of the ipsilateral arm , forced expiratory volume in 1 second ( FEV1 ) , and forced vital capacity ( FVC ) were measured at 4 , 24 , 48 , and 72 hours after the operation . Opioid use was measured during the initial 24 hours after the operation . Results . At 4 hours , the INB+ group demonstrated better FEV1 ( 56.6 % vs. 40.4 % of baseline , P < .05 ) and FVC values ( 54.6 % vs. 39.6 % of baseline , P < .05 ) and less resting and cough pain ( P < .05 ) . However , FEV1 continued to decline in the INB+ group at 24 hours to lower than the INB- group although pain scores were similar beyond 4 hours . Opioid usage during the first 24 hours was similar ( INB- , 16.7 mg vs. INB+ , 13.2 mg , P = .7 ) . Conclusions . Although postoperative INB provided modest improvements in pain and pulmonary function when used as an adjuvant to 0.5 mg SM for post-thoracotomy analgesia , the benefits were transient . The authors do not recommend adding INB for patients undergoing lateral thoracotomy who receive 0.5 mg SM Thirty-one patients undergoing thoracotomy were prospect ively r and omized to receive ( 1 ) no nerve blocks ( n = 12 ) , ( 2 ) placement of percutaneous catheters for intermittent nerve blocks with bupivacaine ( Marcaine ) ( n = 10 ) , or ( 3 ) bupivacaine nerve blocks intraoperatively ( n = 8) . One patient refused postoperative evaluation and was not included in this study . All patients received similar preoperative , intraoperative , and postoperative medications . Comparison of preoperative and postoperative arterial blood gases , assessment s of pain and alertness , and chest roentgenograms showed no statistical advantage for any group . Analgesic requirements and pulmonary functions ( functional residual capacity , tidal volume , minute ventilation peak flow , or forced expiratory volume ) did not differ among the groups . Statistically significant differences were seen in mean respiratory rate and forced vital capacity . These differences , however , indicate that bupivacaine either by intraoperative use or by intermittent percutaneous administration did not improve postoperative increases in respiratory rate or decreases in forced vital capacity Variables of ventilation were obtained preoperatively and during the first two postoperative days in 28 patients after thoracic surgery . All patients received 0.5 % bupivacaine with epinephrine , 5 μg·ml−1 ( 5 - 10 ml ) , through an epidural catheter at the thoracic level supplemented by light general anesthesia . One hour after the initial dose of bupivacaine , patients were r and omly allocated to one of two groups : an epidural ( EP ) sufentanil and an intravenous ( IV ) sufentanil group . Both groups received 0.125 % bupivacaine via continuous epidural infusion postoperatively for three days . In addition , the EP group received 0.83 μg · ml−1 sufentanil added to the epidural infusion of 5 - 10 ml · hour−1 , while the IV group received an identical dose of sufentanil via continuous intravenous infusion of 5 - 10 ml · hour−1 . The ventilatory response to 5 % CO2 was analyzed preoperatively and on postoperative Days 1 and 2 . No significant depression in ventilatory response to CO2 could be detected by measurement of minute ventilation and mouth occlusion pressure at 100 milliseconds ( P0.1 ) . Pain measurement was assessed by blinded observers using the Inverse Visual Analog Scale , where 0 signifies most pain and 10 signifies least pain . The mean scores were above 7 in both groups and were attained at similar analgesic requirements . The incidence of side effects was not different . Only the initial mean sufentanil plasma levels in patients of the IV group were higher than those of the EP group . This study shows that the variables of ventilation were not affected by sufentanil administered via the epidural or the intravenous route , and that both techniques provided excellent pain relief when employed to supplement low-dose 0.125 % bupivacaine epidurally UNLABELLED The management of postthoracotomy pain is a problem and may contribute to atelectasis , leading to hypoxemia , pulmonary infection , and permanent alveolar damage . We sought to determine the efficacy of interpleural analgesia for pain control and to evaluate independent predictors for postoperative pain intensity . Eighty-three patients undergoing elective anterolateral ( n = 37 ) and posterolateral ( n = 46 ) thoracotomy were included in a prospect i ve , r and omized , double-blinded trial . Patients were assigned to receive either 0.5 % bupivacaine or saline solution interpleurally every 4 h for 10 doses postoperatively . All patients also received patient-controlled analgesics ( PCA ) with piritramide as the opioid for additional pain control . Pain was assessed on the basis of PCA requirements and by using a visual analog scale . Visual analog scale scores and PCA requirements were not different between groups . Both interpleural bupivacaine and saline significantly reduced pain scores 30 min after the administration . We concluded that pain reduction by interpleural instillation of bupivacaine reflects a placebo-like effect ; however , interpleural analgesia is not effective in patients undergoing lateral thoracotomy . Sex and surgical approach were shown to influence postoperative pain intensity at rest , but not during coughing . The female patients , and those undergoing posterolateral thoracotomy , exhibited higher pain scores . This observation appears to be of only marginal clinical significance . The efficacy of interpleural analgesia to reduce postoperative pain intensity in patients after lateral thoracotomy is controversial . In this study we demonstrated a lack of efficacy of interpleural analgesia . IMPLICATION S The efficacy of interpleural analgesia to reduce postoperative pain intensity in patients after lateral thoracotomy is controversial . In this study , we demonstrated a lack of efficacy of interpleural analgesia This study was design ed to evaluate the potential fentanyl-sparing effect of a dilute local anesthetic , bupivacaine , administered in fixed combinations with fentanyl for post-thoracotomy analgesia via a continuous thoracic epidural infusion . Forty adult patients scheduled for thoracotomy were r and omly allocated in a double-blind fashion to receive an epidural infusion containing 0 , 0.03 , 0.06 , or 0.125 % bupivacaine in combination with fentanyl ( 4 micrograms/mL ) . The epidural infusions were initiated in the operating room at 10 mL/hr . During the first 24 hours , there were no between-group differences in pain scores . Total fentanyl use was significantly decreased 24 % to 33 % in all bupivacaine treatment groups . However , fentanyl plasma levels at 24 hours were not significantly different between groups . Arterial blood gas measurements performed on the morning after surgery revealed significant reductions in PaCO2 values , 38 + /- 4 , 36 + /- 4 , 37 + /- 4 mmHg for 0.03 , 0.06 , and 0.125 % bupivacaine groups respectively , versus 44 + /- 6 for the plain fentanyl group . Arterial pH values were significantly higher in all bupivacaine treatment groups . These findings suggest that the combination of dilute bupivacaine with fentanyl for thoracic epidural analgesia for post-thoracotomy pain may have beneficial effects on pulmonary gas exchange This double-blind , placebo-controlled study investigated the efficacy of intermittent doses of intrathecal fentanyl in 30 patients undergoing thoracotomy . They were allocated r and omly to three groups , two of which had microspinal catheters inserted into the lumbar subarachnoid space at the end of surgery ; the third group acted as a control . Intrathecal fentanyl or 0.9 % saline was administered through the catheters and all patients received morphine using a patient-controlled analgesia ( PCA ) system . Pain scores , morphine consumption and peak expiratory flow rates ( PEFR ) were recorded on an hourly basis . Intrathecal fentanyl result ed in a faster onset of analgesia ( mean visual analogue scale ( VAS ) score at 1 h = 0.9 compared with 6.3 ( 95 % confidence intervals for the difference -6.8 , -4.0 ) for the other groups ; P < 0.001 ) and significantly lower pain scores at rest , on cough and on movement . PEFR values were consistently higher in the intrathecal fentanyl group . There were no cases of early or delayed respiratory depression BACKGROUND We compared thoracic morphine epidural analgesia ( TEA ) and I.V. analgesia ( IVA ) with morphine , in respect to the time to extubation , the quality of postoperative analgesia , side effects , complications , postoperative hospital length of stay in patients having thoracotomy lung resection . METHODS We prospect ively studied 563 consecutive patients , undergoing thoracotomy ( lobectomy , bilobectomy or pneumonectomy ) , r and omized in two groups : TEA 286 patients and IVA 277 patients . In the epidural group , before the induction of anesthesia , continuous infusion of 15 mg of morphine in 250 mL of normal saline at 5 mL/h was started . In the IVA group a continuous infusion of 30 mg of morphine associated with 180 mg ketorolac in 250 mL of normal saline at 5 mL/h was started before the induction of anesthesia . The pain degree was evaluated on an analogic scale by Keele modified at 1 ( end of anesthesia ) 6 , 12 , 24 , and 48 postoperative hours , at rest and after movements . Data obtained were analysed by means of the analysis of variance for repeated measures . RESULTS The time from the end of surgery to tracheal extubation was similar in both groups . Significantly lower numeric verbal pain scores at rest and after movements were found in the epidural group ( p<0.001 ) . Postop complications , nausea and vomiting were higher in the IVA group ( p<0.05 ) . Postoperative mean hospital length of stay was 9+/-4 days in TEA and 11+/-4 in the IVA group ( p<0.05 ) . CONCLUSIONS In our study the epidural root was superior in terms of analgesia , side effects , length of stay and postoperative complications after thoracotomy Background and Objectives . Combinations of bupivacaine and fentanyl are popular for postoperative epidural analgesia . However , there are little data from which to select a rational dose of bupivacaine . The study examined the effects of increasing amounts of epidural bupivacaine on postoperative analgesia , epidural fentanyl consumption , and side effects after thoracotomy . Methods . Twenty-four patients were r and omized in a double-blind manner to receive intra- and postoperative epidural infusions of either saline , 0.01 % bupivacaine , 0.05 % bupivacaine , or 0.1 % bupivacaine at 10 mL/h . All patients received a st and ardized combined epidural ( 120 mg lidocaine and 1.5 μg/kg of fentanyl ) and general anesthesia . Further postoperative analgesia was provided with fentanyl patient-controlled epidural analgesia ( PCEA ) only . Results . There were no differences between groups in visual analog scale ( VAS ) pain scores at rest or cough , but 10 and 5 mg/h of bupivacaine provided better analgesia during physiotherapy ( P < .05 ) . The use of 10 and 5 mg/h of bupivacaine led to significant opioid sparing ( 50 % decrease ) when compared to saline and 1 mg/h bupivacaine ( P < .03 ) . There was a trend toward a greater incidence of orthostasis with the use of bupivacaine at 10 mg/h ( P = .09 ) . Incidences of opioid side effects were not different between groups . Conclusions . The results demonstrate improved analgesia with physiotherapy and significant opioid sparing when 10 and 5 mg/h doses of bupivacaine are used . However , the incidence of orthostasis may be increased with the use of 10 mg/h . Thus , 5 mg/h of epidural bupivacaine ( .05 % at 10 mL/h ) improved analgesia , decreased opioid requirements , and did not have detectable hemodynamic effects Both epidural and paravertebral blocks are effective in controlling post-thoracotomy pain , but comparison of preoperative and balanced techniques , measuring pulmonary function and stress responses , has not been undertaken previously . We studied 100 adult patients , premedicated with morphine and diclofenac , allocated r and omly to receive thoracic epidural bupivacaine or thoracic paravertebral bupivacaine as preoperative bolus doses followed by continuous infusions . All patients also received diclofenac and patient-controlled morphine . Significantly lower visual analogue pain scores at rest and on coughing were found in the paravertebral group and patient-controlled morphine requirements were less . Pulmonary function was significantly better preserved in the paravertebral group who had higher oxygen saturations and less postoperative respiratory morbidity . There was a significant increase in plasma concentrations of cortisol from baseline in both the epidural and paravertebral groups and in plasma glucose concentrations in the epidural group , but no significant change from baseline in plasma glucose in the paravertebral group . Areas under the plasma concentration vs time curves for cortisol and glucose were significantly lower in the paravertebral groups . Side effects , especially nausea , vomiting and hypotension , were troublesome only in the epidural group . We conclude that with these regimens , paravertebral block was superior to epidural bupivacaine OBJECTIVE To compare the analgesic efficacy of a traditional epidurally delivered bupivacaine/fentanyl combination with a repeat bolus intrathecal morphine technique in the management of post-thoracotomy pain and to assess further the effect of cyclooxygenase ( COX ) inhibition on both modalities . DESIGN Prospect i ve , r and omized , blinded study . SETTING University teaching hospital . PARTICIPANTS Patients having thoracic surgery . INTERVENTIONS Epidural and intrathecal catheters were inserted . Blood and urine sample s were collected for analysis . COX-1 and COX-2 inhibition with ibuprofen and nimesulide ( COX-2 selective ) was instituted . MEASUREMENTS AND MAIN RESULTS Pain was assessed at rest and coughing by visual analog scale . Peak expiratory flow rate , patient satisfaction rating , sedation score , analgesic requirements , and preoperative and postoperative urinary creatinine levels were measured . The spinal and nimesulide combination showed the lowest pain scores ( p < 0.001 ) , least reduction in peak expiratory flow rate ( p < 0.001 ) , and highest patient satisfaction rating ( p = 0.02 ) . COX inhibition did not affect analgesic requirements in the epidural group or increase urinary creatinine in any group . CONCLUSION The intrathecal morphine and nimesulide combination offered significantly better analgesia than any other combination studied . The efficacious interaction between opioids and nonsteroidal anti-inflammatory drugs may be COX-2 mediated Thoracic epidural anesthesia ( TEA ) combined with general anesthesia ( GA ) as well as total-IV anesthesia ( TIVA ) are both established anesthetic managements for thoracic surgery . We compared them with respect to hypoxic pulmonary vasoconstriction , shunt fraction and oxygenation during one-lung ventilation . Fifty patients , ASA physical status II-III undergoing pulmonary resection were r and omly allocated to two groups . In the TIVA group , anesthesia was maintained with propofol and fentanyl . In the TEA group , anesthesia was maintained with TEA ( bupivacaine 0.5 % ) combined with low-dose concentration 0.3–0.5 vol% of isoflurane ( end-tidal ) . Changing from two-lung ventilation to one-lung ventilation caused a significant increase in cardiac output ( CO ) in the TIVA group , whereas no change was observed in the TEA group . One-lung ventilation caused significant increases in shunt fraction in both groups which was associated per definition with a significant decrease in Pao2 in both groups but Pao2 remained significantly increased in the TEA group ( P < 0.05 ) . We conclude that both anesthetic regimens are safe intraoperatively . However , TEA in combination with GA did not impair arterial oxygenation to the same extent as TIVA , which might be a result of the changes in CO . Therefore , patients with preexisting cardiopulmonary disease and impaired oxygenation before one-lung ventilation might benefit from TEA combined with GA BACKGROUND Thoracic epidural analgesia is considered the method of choice for postthoracotomy analgesia , but it is not suitable for every patient and is associated with some risks and side effects . We therefore evaluated the effects of an extrapleural intercostal analgesia as an alternative to thoracic epidural analgesia . METHODS In a prospect i ve , r and omized study , pain control , recovery of ventilatory function , and pulmonary complications were analyzed in patients undergoing elective lobectomy or bilobectomy . Two groups of 15 patients each were compared : one received a continuous extrapleural intercostal nerve blockade ( T3 through T6 ) with bupivacaine through an indwelling catheter , the other was administered a combination of local anesthetics ( bupivacaine ) and opioid analgesics ( fentanyl ) through a thoracic epidural catheter . RESULTS Both techniques were safe and highly effective in terms of pain relief and recovery of postoperative pulmonary function . However , minor differences were observed that , together with practical benefits , would favor extrapleural intercostal analgesia . CONCLUSIONS These results led us to suggest that extrapleural intercostal analgesia might be a valuable alternative to thoracic epidural analgesia for pain control after thoracotomy and should particularly be considered in patients who do not qualify for thoracic epidural analgesia In this double-blind r and omized study we compared a group of 15 patients undergoing thoracotomy who received a spinal injection of sufentanil 20 microg combined with morphine ( 200 microg ) after induction of general anaesthesia with a control group of the same size . Post-operative pain was rated on a visual analogue scale ( VAS ) and a verbal rating scale at rest and with a VAS on coughing . In the recovery room , patients received titrated i.v . morphine until the VAS score was < 30 , and were followed by patient-controlled analgesia ( PCA ) for 72 h. The intrathecal sufentanil and morphine group had a lower intra-operative requirement for i.v . sufentanil and needed less i.v . morphine for titration in the recovery room . I.v . PCA morphine consumption and pain scores were lower in the active group than in the control group during the first 24 h. There were no differences after this time . Spirometric data ( peak expiratory flow , forced vital capacity and forced expiratory volume in 1 s ) were similar in the two groups . We conclude that the combination of intrathecal sufentanil and morphine produces analgesia of rapid onset and with a duration of 24 BACKGROUND Continuous thoracic epidural analgesia is considered by many the gold st and ard for post-thoracotomy pain control but is associated with its own complications . In this study we compare continuous paravertebral extrapleural to epidural infusion for post-thoracotomy pain control . METHODS In a prospect i ve fashion , 50 patients were r and omized to receive either paravertebral or epidural infusion for post-thoracotomy pain control . The anesthesia department placed epidurals , and the operative surgeon placed unilateral paravertebral catheters . Patients were evaluated for analgesic efficacy and postoperative complications . RESULTS We found that both methods of analgesia provide adequate postoperative pain control . Epidural infusion demonstrated an improved efficacy early in the postoperative course but provided statistically similar analgesia to paravertebral by postoperative day 2 . Neither group demonstrated a greater number of pain-related complications . Narcotic-induced complications such as pruritus , nausea/vomiting , and postural hypotension/mental status changes/respiratory depression were seen with statistically similar frequency in both epidural and paravertebral arms . Urinary retention , however , was noted to be significantly more frequent in patients with epidural catheters . Drug toxicity was not observed with either epidural or paravertebral infusion . CONCLUSIONS We recommend continuous paravertebral infusion as an improved method of post-thoracotomy analgesia that can be placed and managed by the surgeon BACKGROUND Thoracic epidural analgesia ( TEA ) is effective in alleviating pain after major thoracoabdominal surgery and may also reduce postoperative mortality and morbidity . This study investigated cardiovascular autonomic control in patients undergoing elective thoracic surgery and its modulation by continuous TEA . METHODS Thirty-eight patients were r and omly assigned to receive patient-controlled analgesia ( PCA group ) or thoracic epidural analgesia ( TEA group ) with doses of bupivacaine ( 0.25 % during operation , 0.125 % after operation ) and fentanyl ( 2 microg ml(-1 ) ) . Heart rate variability ( HRV ) , baroreflex function and pressure response to nitroglycerine and phenylephrine were assessed before operation , 4 h after the end of surgery ( POD 0 ) and on the first and second postoperative days ( POD 1 and POD 2 ) . RESULTS Early after surgery , all HRV variables and baroreflex sensitivities were markedly decreased in both groups . In the TEA group , total HRV and its high-frequency components ( HF ) increased towards preoperative values at POD 1 and POD 2 , whereas the ratio of low to high frequencies ( LF/HF ) was significantly reduced ( mean ( SD ) , -44 (15)% at POD 0 , -38 (17)% at POD 1 , -37 ( 18 % ) at POD 2 ) and associated with blunting of the postoperative increase in heart rate and blood pressure . In the PCA group , the ratio of LF/HF remained unchanged and the decrements in HRV variables persisted until POD 2 . In the two groups , baroreflex sensitivities and pressure responses recovered preoperative values at POD 2 . CONCLUSIONS In contrast with PCA management , TEA using low concentrations of bupivacaine and fentanyl blunted cardiac sympathetic neural drive , result ing in vagal predominance , while HRV variables were better restored after surgery Controversy persists over the efficacy of intercostal nerve block administered through a tunnelled extrapleural catheter . We have undertaken a r and omized , prospect i ve double-blind trial of two different local anaesthetic regimes to evaluate the effect of this technique on post-thoracotomy pain relief and pulmonary function . Sixty-eight patients were r and omized to receive bupivacaine 0.25 % ( n = 22 ) , lignocaine 1 % ( n = 21 ) or 0.9 % NaCl ( saline ) ( n = 20 ) via an extrapleural catheter , inserted peroperatively . All patients underwent a st and ard posterolateral thoracotomy . Pain was assessed using a visual analogue pain score and by the requirement for opiate analgesia . Pulmonary function was measured using bedside spirometry . Pain scores were lower in the local anaesthetic groups at 24 , 32 and 72 h compared with placebo ( P < 0.05 ) and the total amount of opiate required was less than placebo for both lignocaine and bupivicaine ( P < 0.05 ) . Pulmonary function was better in the local anaesthetic groups throughout the post-operative period and was most pronounced at 24 h with a mean improvement of 30 % for forced expiratory volume ( FEV1 ) , 24 % for forced vital capacity ( FVC ) and 19 % for peak expiratory flow rate ( PEFR ) compared with placebo . There was no significant difference between pain scores , opiate requirement or pulmonary function between lignocaine and bupivicaine . CT scanning demonstrated containment of the local anaesthetic in an extra-pleural tunnel . Extra-pleural infusion of local anaesthetics is a simple technique , with low risk of complications and provides effective pain relief as well as an improvement in post-operative pulmonary function . Lignocaine is equally as effective as bupivacaine and its use would result in some cost-saving OBJECTIVE Currently epidural anesthesia is the gold st and ard for postoperative pain management in thoracic surgery . In a prospect i ve r and omised study , the effect of an intercostal nerve block applied at the end of the operation was compared to that of epidural anesthesia . METHODS Thirty patients undergoing thoracotomy were r and omised to each group . Patients with resection of the parietal pleura , rib resection and rethoracotomy were excluded from the study . Both groups received non-steroidal anti-inflammatory drugs every 8h as a baseline analgesic medication and were allowed to ask for supplemental subcutaneous opiate injection , limited to four injections per day . The patients in the epidural catheter group ( group I ) were provided with a motor pump allowing continuous infusion of bupivacain 0.125 % and 2 mg fentanyl/ml at a dosage of 6 - 10 ml per hour , dependent on the pain level over a period of 5 days . The patients of the second group ( group II ) received an intercostal nerve block at the end of the operation reaching from the third to the ninth intercostal space with 20 ml 0.5 % bubivacaine . Pain was evaluated with a pain score ranging from 1 ( no pain ) to 10 ( worst pain ) twice daily in relaxed position and during physical activity like coughing . On the fifth postoperative day , the patients were asked specific questions concerning the subjective pain experience . Costs of both treatments were calculated . Mean pain values and costs of both groups were compared by t-tests for independent sample s. A P value of less than 0.05 was considered significant . RESULTS Eighteen male and 12 female patients , aged between 35 and 71 years ( mean 59 ) were included in the study . Nineteen patients had lobectomy , five bilobectomy , two decortication and three wedge resection . There were 22 right sided and eight left sided procedures . In group I , the mean pain score on the operation day was 3.95 in relaxed position and 6.33 during physical activity like coughing . The mean pain score during the following 4 days was 2.19 in relaxed position and 4.28 with activity . Three patients required additional subcutaneous opiate injection . In group II , the mean score on the operation day was 2.0 in relaxed position and 3.5 during activity . The mean pain score during the next 4 days was 2.84 in relaxed position and 5.65 with activity . Twelve patients received subcutaneous opiates . In both groups , no complications were observed . COSTS The costs for treatment of one patient was 105 in group I and 33 in group II . Patients ' satisfaction was equal in both groups , there were no differences in terms of outcome and recovery . CONCLUSION Pain management by intercostal block was superior during the first 24h after surgery whereas on the second day after surgery pain control was significantly better achieved by the epidural catheter in relaxed position . A combination of both forms of anaesthesia seems to be an ideal pain management in patients undergoing thoracic surgery Forty-five patients who underwent anterolateral and posterolateral thoracotomy were studied to compare the relative efficacy of cryoanalgesia , epidural morphine , intrapleural analgesia , and intravenous morphine for relief of postoperative pain and prevention of deterioration in pulmonary function . Spirometry ( FEV1 , FVC ) was performed preoperatively and postoperatively . Patients ' pain was assessed using the 0 to 100 mm visual analog scale . Because intravenous morphine was used to supplement pain relief in the patients who received intrapleural analgesia and cryoanalgesia , total morphine use was compared to that administered to patients in the intravenous morphine group . Epidural morphine was found to offer better pain relief than the other treatment modalities . There were no differences in spirometric testing between the groups at any time during the study . Although the number of evaluable patients was insufficient to draw definitive conclusions , 12-week follow-up suggested a difference in the incidence of post-thoracotomy pain syndrome in patients who received cryoanalgesia . It is concluded that post-thoracotomy pain is best relieved with epidural morphine , compared to intrapleural analgesia , cryoanalgesia , and parenteral morphine . There was no change in the deterioration in spirometric tests after thoracotomy , nor was there any advantage offered by cryoanalgesia or intrapleural analgesia over intravenous morphine , with respect to pain relief Fifty-one patients scheduled for thoracotomy were included in a study involving five different methods of postoperative analgesia . Forty patients were r and omly divided into : Group C , receiving intramuscular oxycodone on request following an intraoperative intercostal block ; Group IC , intercostal blocks with 0.5 % bupivacaine performed prior to surgery , 6 h later and on the first postoperative morning : Group EB , epidural bupivacaine as a continuous infusion of 0.25 % bupivacaine ( 5 ml h-1 ) ; Group EM4 epidural morphine 4 mg injected prior to surgery and on the first postoperative morning . In addition , a fifth group ( Group EM6 ) of 11 patients received 6 mg of epidural morphine timed as in Group EM4 , but these patients were automatically scheduled to be observed in the ICU . Additional intramuscular oxycodone was given on request to all patients . Group EB , EM4 and EM6 had lower numbers of requests than Group C. Pain intensity score was lowest ( 2.5 on a scale from 0 to 10 , 3 h postoperatively ) in Group EM6 , and there was a statistically significant difference in pain intensity at 3 h between EM4 and EM6 . The evaluation of cooperation and pain by the physical therapist revealed no differences between the groups . Postoperative blood-gas analyses contained slightly elevated PCO2 values ( 6.0 - 7.3 kPa ) in all groups . Postoperatively , only Group EB was devoid of PCO2 values above 7.3 kPa . Urinary retention was a common complication in the patients receiving epidural analgesia , occurring most frequently in Group EM6 ; 10 of the 11 patients had to be catheterized Intrapleural bupivacaine has been reported to be effective for analgesia following cholecystectomy and thoracic surgery . Twenty patients who had a posterolateral thoracotomy were studied in a r and omized , double-blind , placebo-controlled fashion . Patients were assigned to receive intrapleural administration of either 0.5 percent bupivacaine or saline solution every 4 h for 12 doses postoperatively , as well as narcotic analgesics as needed for additional pain control . Pain was assessed using a visual analogue scale . Narcotic analgesic use , duration of hospitalization , and the development of complications were recorded . There were nine evaluable patients who received bupivacaine , and ten patients who received placebo . The age , sex , and type of operation were similar in the two groups , and the procedures were performed by the same two surgeons . The mean pain score at 24 h postoperatively was 5.8 + /- 0.8 in the bupivacaine group and 6.0 + /- 0.6 in the placebo group . At 48 h , the scores were 4.6 + /- 0.8 in the bupivacaine group and 5.1 + /- 0.9 in the placebo group . The mean dose of morphine sulfate or equianalgesic dose of meperidine during the first 24 h was 13.9 + /- 3.7 mg in the bupivacaine group and 12.6 + /- 1.8 mg in the placebo group , and during the next 24 h it was 40.0 + /- 13.4 mg in the bupivacaine group and 38.0 + /- 9.2 mg in the placebo group . The mean duration of hospitalization was 12.8 + /- 3.2 days in the bupivacaine group and 12.1 + /- 2.9 days in the placebo group . Two patients who received bupivacaine and three patients who received placebo had development of pneumonia or atelectasis postoperatively . There was no statistically significant difference in any parameter between those who received bupivacaine and those who received placebo . Thus , there was no subjective or objective clinical benefit of this method of postoperative analgesia compared with placebo following posterolateral thoracotomy The effects of intrapleural ( IP ) bupivacaine on pain , morphine requirement , and pulmonary function were evaluated in 15 patients for 24 hours after thoracotomy . An IP catheter was placed during surgery . Patients were r and omized in a double-blind fashion to receive 1.5 mg/kg of 0.5 % bupivacaine IP or saline on two occasions , eight hours apart . A st and ard anesthetic with thiopental , oxygen , isoflurane , and nondepolarizing muscle relaxant was given . Pain was evaluated with a visual analog pain score every hour , and forced vital capacity ( FVC ) , forced expiratory volume one second ( FEV1 ) , peak expiratory flow ( PF ) , and forced expiratory flow 25 % to 75 % ( FEF ) were measured 1 , 2 , 4 , 8 , and 24 hours postoperatively as well as before and 30 minutes after each IP injection . Arterial blood gases were sample d 1 , 2 , 8 , and 24 hours postoperatively . Plasma bupivacaine concentrations were measured in 10 patients 5 , 10 , 20 , 30 , 60 , 120 , and 180 minutes after IP injection . With each IP bupivacaine injection , the pain score and morphine requirement decreased . There was a significant improvement in all pulmonary function tests in the patients receiving bupivacaine , but no change in the saline controls . The analgesic effect was shortlived ( two to five hours ) , possibly because of loss of bupivacaine in the chest drains . No differences were seen between the two groups after the effect of IP bupivacaine had worn off . Plasma bupivacaine levels had a Cmax of 0.44 to 1.50 micrograms/mL , with a Tmax at 5 to 30 minutes with levels well below 2 to 4 micrograms/mL where increasing toxicity is seen We have investigated the effect of interpleural morphine on postoperative pain and pulmonary function after thoracotomy . At the end of surgery , an interpleural catheter was inserted in 17 patients and , in a double-blind and r and omized manner , either a bolus of morphine 2.5 mg interpleurally ( i.p . ) and normal saline i.v . ( group I ) or , as a control for systemic absorption , morphine 2.5 mg i.v . and i.p . saline ( group II ) was injected . After the initial bolus , a continuous infusion of morphine 0.5 mg h-1 i.p . and saline i.v . ( group I ) or morphine 0.5 mg i.v . and saline i.p . ( group II ) was maintained for 24 h. Postoperative pain was assessed by a visual analogue scale , a numerical rating scale and the McGill Pain Question naire . Pulmonary function was assessed by spirometry . Supplementary analgesics , side effects , degree of sedation , vital signs and chest tube drainage were recorded . All variables were assessed on the day before surgery and 1 , 2 , 3 , 4 , 5 , 6 and 24 h and 7 days after surgery . Supplementary morphine was given upon request . There was no significant difference in any pain measure or postoperative pulmonary function variable between the groups . We conclude that , after thoracotomy , interpleural morphine does not provide superior analgesia or improve pulmonary function compared with systemic morphine OBJECTIVE To compare continuous thoracic epidural analgesia ( TEA ) and paravertebral block ( PVB ) for postoperative analgesia in patients undergoing minimally invasive direct coronary artery bypass ( MIDCAB ) surgery for quality of analgesia , complications , compliance to chest physiotherapy , hemodynamics , and respiratory effects . DESIGN Prospect i ve , r and omized study . SETTING Specialty research hospital . PARTICIPANTS Forty-one consenting patients undergoing MIDCAB surgery . INTERVENTIONS Patients in the TEA group had an epidural catheter inserted at the T4 - 5 interspace , whereas patients in the PVB group had a catheter inserted in the paravertebral space on the left side at the T4 - 5 level . MEASUREMENTS AND MAIN RESULTS Parameters evaluated included visual analog scale pain scores at rest and while coughing , supplemental analgesic requirement , complications , hemodynamics , and respiratory parameters . Measurements were made at 2-hour intervals for 12 hours beginning at 10 minutes after endotracheal extubation . There was no statistically significant difference in visual analog scale scores and requirement of supplemental analgesia between the 2 groups . Cardiac index at 4 hours and 6 hours was significantly higher in the TEA group . Patients in the PVB group had significantly lower respiratory rates at 8 , 10 , and 12 hours . All other parameters were comparable . In 1 patient , the epidural space could not be catheterized . One patient in the TEA group had transient hypotension , and 1 patient complained of backache at the site of the epidural catheter insertion . CONCLUSION PVB is as effective as TEA for postoperative analgesia after MIDCAB surgery . PVB is technically easier than TEA and may be safer than TEA because no complications were seen in the PVB group The analgetic effect of bupivacaine given epidurally or interpleurally after thoracotomy was investigated in a r and omized , double blind , placebo controlled study . 32 patients with both an epidural and an interpleural catheter , were r and omized to receive either interpleural or epidural analgesia . The interpleural group was given bupivacaine 5 mg ml‐1 with 5 microgram epinephrine as a 30 ml interpleural bolus , followed by a continuous infusion starting at a rate of 7 ml per hour and epidurally a bolus of 0.9 % NaCl followed by a continuous infusion of 0.9 % NaCl . The epidural group was given bupivacaine 3.75 mg – ml‐1 with 5 microgram epinephrine as a 5 ml epidural bolus , followed by a continuous infusion starting at a rate of 5 ml per hour and interpleurally a bolus of 0.9 % NaCl followed by a continuous infusion of 0.9 % NaCl . The draining tubes were clamped during the injection of the interpleural bolus and 15 min afterwards . Adequacy of pain relief was evaluated with the Prins – Henry pain scale . Morphine requirement was registered , there was no difference between the groups in painscores or need for additional morphine To assess the efficacy of continuous extrapleural intercostal nerve block on postoperative pain and pulmonary function , a prospect i ve , r and omized , double-blind , placebo-controlled trial was conducted on 56 patients undergoing elective thoracotomy . Infusion was started before closing the chest and was continued for 5 days . Subjective pain relief was assessed on a linear visual analogue scale . Pulmonary function was measured on the day before operation and daily for 5 days . There were 29 patients in a group which received bupivacaine and 27 in a control group which received saline . The bupivacaine group had lower pain scores ( P less than 0.01 ) and required less papaveretum ( P less than 0.01 ) than the control group . Forced vital capacity , forced expiratory volume in 1 s and peak expiratory flow rate were maximally reduced at 24 h to median values of 56 , 60 and 57 per cent , respectively , of preoperative control values in the bupivacaine group , and to 25 , 30 and 32 per cent in the control group . These differences are highly significant ( P less than 0.01 ) . Restoration of pulmonary function was superior in the bupivacaine group ( P less than 0.01 ) . There were no infusion-related complications . After thoracotomy , continuous intercostal blockade with bupivacaine is a safe and effective method of pain relief which reduces the early loss of postoperative pulmonary function significantly and more rapidly restores respiratory mechanics Tramadol , an analgesic deriving only part of its effect via opioid agonist activity , might provide postoperative pain relief with minimal risk of respiratory depression . We , therefore , evaluated it for the control of postthoracotomy pain . In this r and omized , double-blind study , a single intravenous ( IV ) bolus dose of 150 mg tramadol ( Group T ) was compared to epidural morphine administered as an initial 2-mg bolus and subsequent continuous infusion at a rate of 0.2 mg/h ( Group M ) . Patients in each group could receive morphine IV from a patient-controlled analgesia ( PCA ) device . Pain scores , morphine consumption , arterial blood gases , and vital capacity values were recorded at regular intervals postoperatively until 8:00 AM on the first postoperative day . Both groups obtained adequate pain relief , and there were no between-group differences in pain scores or PCA morphine consumption . PaO2 was significantly higher in Group T at 2 h and PaCO2 significantly higher in Group M at 4 h postoperatively . There were no other significant respiratory differences . We conclude that a single dose of 150 mg tramadol given at the end of surgery provided postoperative analgesia equivalent to that provided by this dosage regimen of epidural morphine for the initial postoperative period . ( Anesth Analg 1996;83:87 - 91 Background and Objectives . The effectiveness of a continuous infusion of extrapleural bupivacaine for relief of postoperative pain was assessed in patients undergoing posterolateral thoracotomy under general anesthesia by comparing morphine requirements . Methods . Bupivacaine 0.25 % was infused at a rate of 5 mL/h through an unkinkable extrapleural catheter that was sited under direct vision at operation . Results . Mean ( ± SD ) 24-hour requirements for morphine from a patient-controlled analgesia device were 39 ± 15 mg for the treated group and 69 ± 26 mg in the control group ( P < .006 ) . Patients in the treated group recorded significantly smaller visual analog scores for pain both at rest ( P < .005 ) and on movement ( P < .03 ) compared to the control group . There were no adverse effects associated with the use of extrapleural bupivacaine in this study . Conclusions . Continuous extrapleural infusion of bupivacaine through unkinkable catheters sited during thoracotomy result ed in decreased intravenous patient-controlled analgesia use and decreased verbal categoric pain scores at rest and during movement Background : We have documented that adrenaline 2.0 µg·ml− 1 markedly improves relief of dynamic pain when added to a thoracic epidural analgesic infusion of bupivacaine 1 mg·ml− 1 and fentanyl 2 µg·ml− 1 . Concern about possible adverse effects on spinal cord blood flow , expressed by others , prompted us to find the lowest concentration of adrenaline needed to produce effective and reliable pain relief after major surgery This study compared epidural and intravenous fentanyl infusions for pain relief for the first 20 h after thoracotomy , in order to examine whether an thoracic epidural fentanyl infusion offers clinical advantage over an intravenous infusion . Forty patients were assigned r and omly to receive either fentanyl epidurally and saline intravenously or fentanyl intravenously and saline epidurally in a double-blind fashion . For each patient the fentanyl infusion was titrated to a rate required for pain relief ( pain score less than 3 , maximum 10 ) . Patients reported similar median pain scores , but in the epidural group the required mean fentanyl infusion rate was less ( 0.95 + /- 0.23 vs. 1.67 + /- 0.46 micrograms.kg-1.h-1 , P = 0.0001 ) and plasma fentanyl concentrations were less at 4 and 18 h ( 4 h : 0.81 + /- 0.27 vs. 1.38 + /- 0.36 ng.ml-1 , P = 0.0001 ; 18 h : 0.94 + /- 0.32 vs. 1.54 + /- 0.65 ng.ml-1 , P = 0.0007 ) than those in the intravenous group . Respiratory function was better preserved and the incidence of nausea and sedation was less in the epidural group than in the intravenous group . In conclusion there appears to be a clinical advantage to the epidural infusion over the intravenous infusion of fentanyl for analgesia after thoracotomy OBJECTIVE To determine dependent chest tube losses of bupivacaine with paravertebral versus interpleural administration , thereby helping to explain the significant differences in pulmonary function that exist between these two techniques . DESIGN A prospect i ve , r and omized study . SETTING A single hospital . PARTICIPANTS Twelve adult patients undergoing posterolateral thoracotomies . INTERVENTIONS Paravertebral or interpleural administration of bupivacaine . MEASUREMENTS AND MAIN RESULTS Analgesia , as assessed by visual analog pain scores and patient-controlled morphine requirements , was similar in both groups . Postoperative spirometric values were significantly better at most times with the paravertebral route of administration . Dependent chest tube bupivacaine losses were approximately four times higher in the interpleural group . CONCLUSION Local anesthetic on the diaphragm might actively impair respiratory function through diaphragmatic and abdominal muscle weakness , while failing to contribute to pain relief We have shown that epinephrine markedly improves the analgesic effect of a thoracic epidural infusion of bupivacaine and fentanyl . Ropivacaine has an intrinsic vasoconstrictive effect , and epinephrine may therefore not have the same pharmacokinetic interaction in a ropivacaine-fentanyl infusion ; but a possible spinal cord & agr;2-agonist effect of epinephrine would give the same positive pharmacodynamic interaction with ropivacaine and fentanyl during epidural analgesia . In a prospect i ve , r and omized , crossover study , a thoracic epidural infusion of ropivacaine 1 mg/mL and fentanyl 2 & mgr;g/mL with or without epinephrine 2 & mgr;g/mL was given to 12 patients in a double-blinded manner after major thoracic or upper abdominal surgery . Main outcome measures were pain intensity at rest and when coughing , evaluated on a visual analog scale . Extent of sensory blockade was evaluated by determining dermatomal hypoesthesia to cold . Pain increased ( P < 0.001 ) and hypoesthetic dermatomal segments decreased ( P < 0.001 ) when epinephrine was omitted from the triple epidural infusion . After 3 h without epinephrine , pain intensity when coughing was unacceptable despite rescue analgesia . After restarting the triple epidural mixture with epinephrine , pain was again reduced to mild pain when coughing , and the sensory blockade was restored . The mixture with epinephrine caused less nausea and facilitated mobilization . We conclude that epinephrine improves the pain relief and reduces the side effects of a thoracic epidural infusion of ropivacaine and fentanyl after major thoracic or upper abdominal surgery In this study the effects of nicomorphine , administered either intramuscularly or by high thoracic epidural route , on the ventilatory and airway occlusion pressure response to CO2 were investigated and compared . Twenty‐four patients scheduled for thoracic surgery were allocated r and omly to postoperative pain relief by i.m . nicomorphine or by high thoracic epidural nicomorphine . The ventilatory response to 5 % carbon dioxide was measured in all patients : first 1 day before operation , secondly on the first day after surgery immediately before nicomorphine administration and finally after the administration , at the moment when no further rise in end‐tidal Pco2 ( Petco2 ) was measured . Respiratory response was assessed in two ways , by measuring minute ventilation ( Ve ) and mouth occlusion pressure ( p0.1 ) . There was a significant depression in ventilatory response to CO2 in the intramuscular group ( P = 0.03 ) due to nicomorphine as assessed by the slope of Ve vs PetCO2 No significant depression was found in the epidural group , irrespective of measurement of VE , or P0.1 . No significant shift of apnoeie threshold‐PETco2 was observed in either group Background : Pain following thoracotomy is frequently associated with clinical ly important abnormalities of pulmonary function . The aim of the current study was to compare the efficacy of continuous thoracic epidural analgesia ( EDA ) to continuous intercostal ( IC ) block for postoperative pain and pulmonary function in a prospect i ve , r and omized , double‐blinded clinical trial BACKGROUND Post-thoracotomy pain causes severe impairment of the respiratory function . Epidural analgesia is effective in the treatment of post-thoracotomy pain but may give rise to significant side-effects . Other low-risk and cost-effective analgesic treatments are therefore required . METHODS Thirty male patients who had undergone pulmonary lobectomy entered a prospect i ve , r and omized trial to evaluate the efficacy of ketorolac tromethamine ( Group 2 ) and extrapleural intercostal nerve block ( Group 3 ) with intermittent low-dose bupivacaine . Objective and subjective assessment was carried out at 8 , 16 , 24 and 48 hours postoperatively . RESULTS There were no significant differences between Groups 1 ( control group ) and 2 . Vital capacity was significantly lower in Group 3 ( p<0.05 ) than in Group 1 after 16 hours . Forced Vital Capacity was significantly higher in Group 2 than in Group 3 after 16 and 24 hours ( p<0.05 ) . Peak expiratory flow was also significantly better in Group 2 than in Group 3 after 16 hours ( p<0.05 ) . On-dem and opioid consumption was significantly lower in Group 2 ( p<0.001 ) and Group 3 ( p<0.05 ) . No side-effects were observed . CONCLUSIONS Ketorolac tromethamine was effective in the treatment of post-thoracotomy pain . Extrapleural intercostal nerve block allowed a significant reduction in the consumption of opioids . These analgesic techniques could be useful as low-risk , cost-effective and reproducible treatments when more effective techniques , such as epidural analgesia , are contraindicated Forty-five patients were allocated r and omly to receive either a single intrathoracic block of four intercostal nerves , a continuous thoracic extradural infusion or a continuous paravertebral infusion of bupivacaine . Patients were allowed additional i.v . boluses of morphine via a PCA device . Segmental spread of pinprick analgesia was comparable in the groups for up to 20 h. Up to 2 h after the block , plasma concentrations of bupivacaine were greater in the intercostal group and there was large interindividual variation . There were no significant differences between the groups in pain , morphine consumption , respiratory function or adverse events . Moderate to severe respiratory depression was detected in 14 patients more than 2 h after operation Background : Basic pharmacological research indicates that there are synergistic antinociceptive effects at the spinal cord level between adrenaline , fentanyl and bupivacaine . Our clinical experience with such a mixture in a thoracic epidural infusion after major surgery confirms this . The objectives of the present study were to evaluate the effects on postoperative pain intensity , pain relief and side effects when removing adrenaline from this triple epidural mixture Pain was controlled in 20 post-thoracotomy patients using a continuous infusion of 0.25 % bupivacaine through an extradural or para-vertebral catheter . Both techniques provided good analgesia . Hypotension and urine retention occurred significantly less frequently in the paravertebral than in the extradural group A r and omized , double-blind trial was conducted to determine the effectiveness of intrapleural bupivacaine hydrochloride in the management of pain after thoracotomy . Thirty-three men and 7 women with a mean age of 62 years ( range , 21 to 76 years ) undergoing elective posterolateral thoracotomy were r and omly allocated preoperatively to either a study group receiving 20 mL of 0.25 % bupivacaine or a control group receiving 20 mL of 0.9 % saline solution through a pleural catheter every 4 hours . Patients received supplementary doses of intramuscular papaveretum as required . Assessment of pain , somnolence , and breathing capacity was performed after the intrapleural injections at 4 , 24 , 48 , and 72 hours postoperatively . Pain assessment , as measured by a linear analog scale , was lower in the bupivacaine group at all times , reaching significance at 4 , 24 , and 72 hours ( p less than 0.05 ) . The forced vital capacity and forced expiratory volume in 1 second at 6 weeks postoperatively remained significantly lower than preoperatively ( p less than 0.05 ) . The fall in forced vital capacity from this postoperative level was significantly less in the bupivacaine group at 4 , 24 , and 48 hours , and the fall in forced expiratory volume in 1 second was significantly less at 4 and 48 hours in the treated group . When used in conjunction with doses of parenteral narcotic , intrapleural bupivacaine gives better pain control with less respiratory depression than intermittent doses of narcotic alone The value of intrapleural analgesia after thoracotomy is still controversial . We investigated the pharmacokinetics of interpleural analgesia in 14 patients with and without thoracic drainage ( Groups TD+ and TD- , respectively ) to determine the safety of the technique . The infusion led to a high steady-state concentration ( Css ) of 5.91 + /- 2.46 mg/mL in Group TD- . We then performed a placebo-controlled double-blind study on 16 patients to evaluate the analgesic effects of an interpleural infusion of 2 % lidocaine using intravenous patient-controlled analgesia ( PCA ) with morphine and a visual analog scale score ( VAS ) . In both studies an initial bolus of 3 mg/kg of 2 % lidocaine was followed by an infusion of 1 mg.kg-1.h-1 for 48 h. The VAS score was slightly reduced after the bolus ( 6.6 + /- 1.0 vs 8.7 + /- 0.3 ; P < 0.05 vs the placebo group ) but the cumulative doses of morphine were similar in both groups . There was a slight , but not sustained , improvement in pulmonary function test . In conclusion , interpleural analgesia by continuous infusion of lidocaine is poor after thoracotomy and may lead to blood levels in the toxic range OBJECTIVE To compare the analgesic effects of intrapleural and intravenous morphine administration for postthoracotomy pain management . DESIGN R and omized , prospect i ve trial . SETTING University teaching hospital . PARTICIPANTS Twenty-eight consenting patients scheduled for elective thoracotomy operations . INTERVENTIONS Patients were r and omly allocated into two groups to receive either 20 mg of intrapleural morphine ( IPM group ) or 20 mg of intravenous morphine ( IVM group ) at the end of the operation . Plasma morphine levels , arterial pressures , heart rate , verbal analog scale ( VAS ) , respiratory rate , and PaCO2 levels were compared in two groups . MEASUREMENTS AND MAIN RESULTS Plasma morphine levels were significantly higher in the IVM group at the 5th minute until the 2nd postoperative hour . VAS was significantly higher in the IVM group . Respiratory rates were significantly higher in the IPM group , whereas PaCO2 remained significantly lower than in the IVM group . CONCLUSIONS IPM achieved better analgesia than IVM and this effect is probably attributable to peripheral effects of morphine We compared continuous IV tramadol as an alternative to neuraxial or systemic opioids for the management of postthoracotomy pain in a prospect i ve , r and omized , double-blinded , controlled study . General anesthesia was supplemented by thoracic epidural analgesia with 0.25 % bupivacaine . At rib approximation , patients received one of the following : IV tramadol ( 150-mg bolus followed by infusion , total 450 mg/24 h , n = 29 ) , epidural morphine ( 2 mg , then 0.2 mg/h , n = 30 ) , or patient-controlled analgesia ( PCA ) morphine only ( n = 30 ) . All patients received PCA morphine and rescue morphine as necessary postoperatively . For the first 24 h , pain and sedation scores and respiratory , cardiovascular , and side effect measures were monitored . There was no significant difference in pain scores and PCA morphine use between tramadol and epidural morphine . Pain scores at rest and on coughing were lower in the Tramadol and Epidural Morphine groups than in the PCA Morphine group at various time points over the first 12 h. The Tramadol and Epidural Morphine groups used significantly less hourly PCA morphine than the PCA Morphine group at specific time points in the first 10 h. Vital capacities in the Tramadol group were significantly closer to baseline values at the 20-h point than in the PCA Morphine group . We conclude that an intraoperative bolus of tramadol followed by an infusion was as effective as epidural morphine and avoided the necessity of placing a thoracic epidural catheter OBJECTIVE Thoracotomy results in severe pain and deleterious changes in pulmonary physiology . The literature suggests that these alterations in pulmonary mechanics are inevitable and can only be minimised but not prevented by effective analgesia . We have re-evaluated this concept and assessed the efficacy of pre-emptive analgesia [ preincisional afferent block , premedication with opiate and /or non-steroidal anti-inflammatory drug ( NSAID ) ] in conjunction with postoperative extrapleural continuous intercostal nerve block on postoperative pain and pulmonary function . MATERIAL S AND METHODS A prospect i ve r and omized study was conducted on 56 patients undergoing elective thoracotomy . Subjective pain relief was assessed on a linear visual analogue scale . Pulmonary function was measured on the day before operation and 12 hourly for 48 hours after operation . There were seven patients in each of the eight groups . RESULTS The balanced analgesia group comprising preincisional block and premedication with opiate and NSAID ( Group 1 ) had significantly better analgesia , needed less postoperative supplementary analgesics and maintained their preoperative pulmonary function postoperatively irrespective of the nature of the operation . The ranking of importance of the three components of the pre-emptive analgesia as assessed in this study are preincisional block , opiate premedication and premedication with NSAID 's . No significant change in plasma levels of cortisol or glucose occurred in Group 1 patients from prior to induction of anaesthesia to 24 hours postoperatively , suggesting effective somatic and sympathetic afferent blockade had been achieved in these patients . There were no complications related to the infusion or the use of NSAID 's . CONCLUSIONS We conclude that a balanced analgesic regime comprising preoperative pain prophylaxis and postoperative maintenance analgesia by NSAID and continuous extrapleural intercostal nerve block will minimise and even reverse the expected decline in lung function after thoracotomy . The postoperative decline in lung function is not obligatory but primarily due to incisional pain and thus is preventable by effective analgesia . An ideal balanced pre-emptive analgesic regime should include preincisional local anaesthetic afferent block and premedication with opiates and a NSAID We investigated analgesia and the adverse effects of epidural sufentanil infusion in a double-blind r and omized study of 37 patients undergoing thoracic surgery . Sufentanil 1 micro gram/mL was administered at a thoracic ( Ts , n = 12 ) or lumbar level ( Ls , n = 11 ) , or combined with bupivacaine 1 mg/mL at a thoracic level ( Tsb , n = 14 ) . Postoperatively , the epidural infusion rate was titrated ( 4 - 20 mL/h ) according to the visual analog pain scale when assessed during function ( VAS-F ) or the occurrence of side effects . When epidural analgesia failed , nonsteroidal antiinflammatory drugs ( NSAIDs ) were given . VAS-F was lowest in the Tsb group ( Tsb < Ts = Ls ) despite its having both the lowest rate of epidural infusion ( Tsb < Ts < Ls ) and need of additional NSAIDs ( Tsb < Ts = Ls ) . Sedation ( Tsb < Ts < Ls ) and hypercapnia ( Tsb = Ts < Ls ) occurred most frequently in the Ls group . Vital capacity ( VC ) was reduced in all groups by 43%-58 % ( Ls > Ts ) and had recovered only partially at 24 h after discontinuation of the epidural infusion . The slopes of the ventilatory response ( minute ventilation [ VE ] , inspiratory flow , and mouth occlusion pressure at 0.1 s [ P0.1 ] ) to 7 % CO2 decreased during treatment in Ls , Ts , and Tsb groups at the most by 73 % , 55 % , and 52 % ( not significant [ NS ] between groups ) , 59 % , 45 % , and 38 % ( NS between groups ) , and 81 % , 43 % , and 18 % ( Ls > Tsb ) , respectively . Twenty-four hours after discontinuation of the epidural infusion , there was a complete recovery of the VE , inspiratory flow , and P0.1 response to CO2 in the Tsb group only . The study shows that , after thoracotomy , epidural sufentanil analgesia is optimal when tailored to the site of nociceptive input and combined with bupivacaine . ( Anesth Analg 1996;83:394 - 400 We studied the comparative effects of ketorolac versus bupivacaine supplementation of hydromorphone ( HM ) patient-controlled epidural analgesia ( PCEA ) on the HM requirement , postoperative pain , and pulmonary function in 62 consenting patients after thoracotomy procedures . Patients were r and omly assigned to receive one of three different combinations of analgesic medications after the operation according to a double-blind , placebo-controlled study . The treatment groups consisted of : Group 1 ( n = 23 ) : PCEA HM 3-mL ( 0.15 mg ) bolus doses + saline 1 mL intravenously ( IV ) q6h , Group 2 ( n = 20 ) : PCEA HM ( 0.15 mg ) in 0.125 % bupivacaine 3-mL bolus doses + saline 1 mL IV q6h , and Group 3 ( n = 19 ) : PCEA HM 3-mL ( 0.15 mg ) bolus doses + ketorolac 1 mL ( 30 mg ) IV q6h . Epidural HM and supplemental analgesic requirements , pain visual analog scale ( VAS ) scores , the incidence of nonincisional pain , and side effects were recorded at 24 and 48 h after surgery . Bedside pulmonary function tests were performed using a Puritan Bennett 100[TM ] ( Puritan-Bennett Corp. , Wilmington , MA ) spirometer before and 24 and 48 h after surgery . IV ketorolac supplementation of HM PCEA significantly reduced the incidence of nonincisional pain and the HM requirement over 48 h compared with the HM PCEA alone group ( 7 % vs 26 % ; 3 + /- 1.6 mg vs 5.3 + /- 2.8 mg ) . Both ketorolac and bupivacaine supplementation of HM PCEA reduced the severity of pain on coughing and on movement compared with HM PCEA alone on postoperative day ( POD ) 1 . Significant reductions in forced vital capacity , forced expiratory volume in 1 s , forced expiratory flow 25%-75 % of the vital capacity , and peak expiratory flow rate ( PEFR ) were noted on PODs 1 and 2 in all three treatment groups . The decrease in PEFR on PODs 1 and 2 was significantly less with ketorolac compared with bupivacaine supplementation . We conclude that ketorolac supplementation of HM PCEA reduces the incidence of nonincisional pain and HM requirement compared with HM PCEA alone and may have a beneficial effect on pulmonary function compared with bupivacaine supplementation of HM PCEA in postthoracotomy patients . ( Anesth Analg 1997;84:564 - 9 A prospect i ve study was carried out in 120 patients undergoing elective thoracotomy for parenchymal disease . Patients were r and omized into three groups : A ( control group ) , B ( epidural analgesia ) , C ( freezing of intercostal nerves ) . Subjective pain relief was assessed on a linear visual analog scale . Analgesic requirements were evaluated during the 12 days following surgery , or until discharge if earlier . The vital capacity ( VC ) and forced expiratory volume in 1 s ( FEV1 ) were measured on the day before operation and on the 1st , 2nd , 3rd and 7th postoperative days ( POD ) . Subjective pain relief was significantly better in Group B in comparison with Group A ( P < 0.05 ) or C ( P < 0.05 ) . Group C had the lowest score on the 11th and 12th POD but differences were not statistically significant . Requirements for intravenous analgesics were lower in Group B than in the control group ( P < 0.05 ) during the first 3 POD , and in group C than in the control group the day of operation ( P < 0.05 ) . Oral analgesic requirements , when compared with controls , were lower in group B during the first 5 POD , and lower in group C on the 3rd and the 4th POD ( P < 0.05 ) . Cryoanalgesia led to a slight but not significant increase in VC and FEV1 . Epidural analgesia led to a significant increase when compared with controls in FEV1 during the first 3 POD , and in FVC on the 7th POD ( P < 0.05 ) . It is concluded that epidural analgesia led to the best pain relief and restoration of pulmonary function after thoracotomy . ( ABSTRACT TRUNCATED AT 250 WORDS |
12,920 | 28,977,091 | The most effective training protocol consists of SEPFM by digital palpation combined with biofeedback monitoring and vaginal cones , including 12 week training parameters , and ten repetitions per series in different positions compared with SEPFM alone or a lack of treatment | INTRODUCTION Strengthening exercises for pelvic floor muscles ( SEPFM ) are considered the first approach in the treatment of stress urinary incontinence ( SUI ) .
Nevertheless , there is no evidence about training parameters .
OBJECTIVE To identify the protocol and /or most effective training parameters in the treatment of female SUI . | Background and Purpose Although surgery has been widely accepted as the treatment of choice for stress urinary incontinence ( SUI ) , there has recently been an increased interest in the conservative management of this condition . The aims of this study were to test the ability of a biofeedback-assisted pelvic-floor muscle exercise ( PFME ) program to affect symptoms of SUI in premenopausal women and to evaluate a training program that might lead to successful outcomes in a relatively limited number of sessions . Subjects Twenty-six women with SUI were treated with PFME with surface electromyography (sEMG)–assisted biofeedback . All participants were of reproductive age and were treated individually for 12 sessions . Methods Results were evaluated with a 7-day voiding diary , a 1-hour pad test , pelvic-floor muscle strength measurements , sEMG amplitudes , a leakage index , and a quality -of-life question naire . These variables were compared before and after the intervention . Results The frequency of urine loss , the occurrence of nocturia , and the number of pads required decreased significantly after the intervention . Objective cure was found in 61.5 % of women . There was a significant improvement in the quality of life , in pelvic-floor muscle strength , and in the sEMG amplitudes of all contractions throughout the intervention . Discussion and Conclusion A relatively short-term intervention of PFME with sEMG-assisted biofeedback appeared to be helpful in relieving symptoms of SUI in premenopausal women and represents a reasonable conservative management option PURPOSE To compare the effectiveness of pelvic floor exercises , electrical stimulation , vaginal cones , and no active treatment in women with urodynamic stress urinary incontinence . PATIENTS AND METHODS One hundred eighteen subjects were r and omly selected to recieve pelvic floor exercises ( n=31 ) , ES ( n=30 ) , vaginal cones ( n=27 ) , or no treatment ( untreated control ) ( n=30 ) . Women were evaluated before and after completion of six months of treatment by the pad test , quality of life question naire ( I-QOL ) , urodynamic test , voiding diary , and subjective response . RESULTS In the objective evaluation , we observed a statistically significant reduction in the pad test ( p=0.003 ) , in the number of stress urinary episodes ( p<0.001 ) , and a significant improvement in the quality of life ( p<0.001 ) in subjects who used pelvic floor exercises , electrical stimulation , and vaginal cones compared to the control group . No significant difference was found between groups in the urodynamic parameters . In the subjective evaluation , 58 % , 55 % , and 54 % of women who had used pelvic floor exercises , electrical stimulation , and vaginal cones , respectively , reported being satisfied after treatment . In the control group , only 21 % patients were satisfied with the treatment . CONCLUSION Based on this study , pelvic floor exercises , electrical stimulation , and vaginal cones are equally effective treatments and are far superior to no treatment in women with urodynamic stress urinary incontinence Background Stress urinary incontinence ( SUI ) is a prevalent and costly condition which may be treated surgically or by physical therapy . The aim of this review was to systematic ally assess the literature and present the best available evidence for the efficacy and effectiveness of pelvic floor muscle training ( PFMT ) performed alone and together with adjunctive therapies ( eg biofeedback , electrical stimulation , vaginal cones ) for the treatment of female SUI . Methods All major electronic sources of relevant information were systematic ally search ed to identify peer- review ed English language abstract s or papers published between 1995 and 2005 . R and omised controlled trials ( RCTs ) and other study design s eg non-r and omised trials , cohort studies , case series , were considered for this review in order to source all the available evidence relevant to clinical practice . Studies of adult women with a urodynamic or clinical diagnosis of SUI were eligible for inclusion . Excluded were studies of women who were pregnant , immediately post-partum or with a diagnosis of mixed or urge incontinence . Studies with a PFMT protocol alone and in combination with adjunctive physical therapies were considered . Two independent review ers assessed the eligibility of each study , its level of evidence and the method ological quality . Due to the heterogeneity of study design s , the results are presented in narrative format . Results Twenty four studies , including 17 RCTs and seven non- RCTs , met the inclusion criteria . The method ological quality of the studies varied but lower quality scores did not necessarily indicate studies from lower levels of evidence . This review found consistent evidence from a number of high quality RCTs that PFMT alone and in combination with adjunctive therapies is effective treatment for women with SUI with rates of ' cure ' and ' cure/improvement ' up to 73 % and 97 % respectively . The contribution of adjunctive therapies is unclear and there is limited evidence about treatment outcomes in primary care setting s. Conclusion There is strong evidence for the efficacy of physical therapy for the treatment for SUI in women but further high quality studies are needed to evaluate the optimal treatment programs and training protocol s in subgroups of women and their effectiveness in clinical practice Biofeedback is a method of pelvic floor rehabilitation using a surface electrode inserted into the vagina and a catheter in the rectum . Forty women with genuine urinary stress incontinence were r and omized to compare the efficacy of physiotherapy and physiotherapy in combination with biofeedback . The effect of the treatment was determined by a st and ardized pad-weighing test . Long-term status was determined using a question naire after 2–3 years . Thirty-four women completed the treatment . The study showed a statistically significant better improvement in the biofeedback group . The long-term effect in the biofeedback group seemed better and the patients were more motivated for training afterwards 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 : The aim of this study was to compare the effectiveness of multimodal supervised physiotherapy programs with the absence of treatment among women with persistent postnatal stress urinary incontinence . METHODS : This was a single-blind r and omized controlled trial . Sixty-four women with stress urinary incontinence were r and omly assigned to 8 weeks of either multimodal pelvic floor rehabilitation ( n = 21 ) , multimodal pelvic floor rehabilitation with abdominal muscle training ( n = 23 ) , or control non – pelvic floor rehabilitation ( n = 20 ) . The primary outcome measure consisted of a modified 20-minute pad test . The secondary outcome measures included a Visual Analog Scale describing the perceived burden of incontinence , the Urogenital Distress Inventory , the Incontinence Impact Question naire , and pelvic floor muscle function measurements . RESULTS : Two patients dropped out , leaving 62 for analysis . At follow-up , more than 70 % of the women in the treatment groups ( 14/20 in the pelvic floor and 17/23 in the pelvic floor plus abdominal group ) were continent on pad testing compared with 0 % of women in the control group . Scores on the pad test , Visual Analog Scale , Urogenital Distress Inventory , and Incontinence Impact Question naire improved significantly in both treatment groups ( all P < .002 ) , whereas no changes were observed in the control group . Pelvic floor muscle function , however , did not improve significantly in either active group . CONCLUSION : Multimodal supervised pelvic floor physiotherapy is an effective treatment for persistent postnatal stress urinary incontinence . LEVEL OF EVIDENCE : Purpose : The aim of this study was to investigate and compare the short-term effects of a physical therapy program in patients with different intensities of urodynamic stress urinary incontinence ( USI ) . Subjects and Methods : 48 patients with USI were assigned to three groups according to the intensity of their incontinence : group I : 0–2 g ( n = 17 ) , group II ( mild intensity : > 2–10 g , n = 16 ) and group III ( moderate intensity : > 10 g , n = 15 ) as determined by the 1-hour pad test . A physical therapy program composed of Kegel exercises and interferential current was applied to all patients for duration of 5 weeks , with a total of 15 sessions . The number of pads used a day , frequency of voiding ( times/day ) , amount of urinary leakage according to the 1-hour pad test ( mg ) , severity of complaint ( as centimeters on visual analogue scale ) and pelvic floor muscle strength ( cm Hg ) were evaluated . Pre-treatment and post-treatment values of these data were compared in each group and among groups . Results : Analyses of the data indicated that the number of pads used a day , frequency of voiding and amount of urinary leakage decreased and pelvic floor muscle strength increased significantly in each group ( p < 0.05 ) . Cure in USI was found in 88 % of subjects in group I and 18 % of subjects in group II ( mild intensity ) . None of the patients in group III ( moderate intensity ) showed a cure effect . Conclusion : This physical therapy program was found to be more effective in mild and moderate intensities than severe USI Introduction and hypothesisPelvic floor muscle training ( PFMT ) is considered to be the first-line treatment for female stress urinary incontinence ( SUI ) . There are few studies that have tested the efficacy of unsupervised PFMT . The aim of this study was to compare the effectiveness of intensive supervised PFMT to unsupervised PFMT in the treatment of female SUI . Methods Sixty-two women with SUI were r and omized to either supervised or unsupervised PFMT after undergoing supervised training sessions . They were evaluated before and after the treatment with the Oxford grading system , pad test , quality of life question naire , subjective evaluation , and exercise compliance . Results After treatment , there were no differences between the two groups regarding PFM strength ( p = 0.20 ) , International Consultation on Incontinence Question naire-Short Form score ( p = 0.76 ) , pad test ( p = 0.78 ) , weekly exercise compliance ( p = 0.079 ) , and subjective evaluation of urinary loss ( p = 0.145 ) . Conclusions Both intensive supervised PFMT and unsupervised PFMT are effective to treat female SUI if training session is provided CONTEXT AND OBJECTIVE Urinary incontinence is a public health problem that affects more than 200 million people worldwide . Stress incontinence is the most prevalent type . Pelvic floor muscle exercises have been used for treating it , although there is no consensus regarding their application . The aim of this study was to compare the results from treating female stress urinary incontinence with pelvic floor muscle exercises with or without physiotherapist supervision . DESIGN AND SETTING This was a r and omized , prospect i ve , controlled trial in the Urogynecology and Vaginal Surgery Sector , Universidade Federal de São Paulo . METHODS Forty-four women were r and omized to be treated for stress urinary incontinence with pelvic floor exercises for three consecutive months , into two groups : one with and the other without physiotherapist supervision . They were evaluated before and after treatment using a quality -of-life question naire , pad test , micturition diary and subjective evaluation . Descriptive analysis was used to evaluate the population . The homogeneity of the two groups was evaluated using the Kruskal-Wallis and Chi-squared tests . The success of the two groups after treatment was evaluated using the Wilcoxon test . RESULTS The supervised group showed statistically greater improvement in the pad test , micturition diary and quality of life than did the control group . In the subjective evaluation , only 23.8 % of the control group patients were satised with their treatment . In the supervised group , 66.8 % of patients did not want any other treatment . CONCLUSION Supervised pelvic floor muscle exercises presented better results in objective and subjective evaluations than did unsupervised exercises We investigated the effectiveness of pelvic floor muscle ( PFM ) exercises or biofeedback for the treatment of urinary stress incontinence ( USI ) . Fifty patients with USI were included in this r and omized , controlled , prospect i ve study . Twenty patients were taught PFM exercises via digital palpation and instructed to perform regularly as home program . The second group of 20 patients had PFM exercises via biofeedback three times a week for 2 months . The third group of 10 patients did not have any exercises . The patients were evaluated via pad test , perineometry , digital palpation based PFM strength , incontinence frequency , and visual analog scale based social activity index prior to and 8 weeks after the treatment . The first two groups had significant improvement in USI with respect to the control group ( p < 0.001 ) . The rise in PFM strength with perineometry of the biofeedback group was higher than in the digital palpation group after treatment ( p < 0.001 ) . PFM exercises are effective for the treatment of USI ; the biofeedback method revealed better PFM strength results with respect to digital palpation OBJECTIVE To compare the effects ofthree different pelvic floor muscle training ( PFMT ) in stress urinary incontinence ( SUI ) women . MATERIAL AND METHOD Sixty-eight eligible SUI women who could perform pelvic floor muscle contraction correctly were r and omly allocated to the three diferent PFMT protocol s , exercise every day ( GJ ) , exercise three days per week ( G2 ) , and exercise plus abdominal training three days per week ( G3 ) . The primary outcome was pad test . The secondary outcomes were pelvic floor muscle strength , and treatment satisfaction . The outcomes were evaluated before and after a 12-week of exercise . RESULTS The weights ofpad were decreased by 2.6 + /- 0.8 , 2.3 + /- 1.3 , and 3.1 + /- 1.3 grams for group 1 , 2 , and 3 , respectively . There was no statistical significant difference among the three groups . The pelvic floor muscle strength was increased by 18.4 + /- 2.7 , 13.9 + /- 2.9 , and 17.3 + /- 3.0 cmH2O for group 1 , 2 , and 3 , respectively , with statistical significant difference among groups ( p < 0.00 ) . The increased muscle strength in group 2 was significant less than the other two groups ( p < 0.00 ) . Treatment Satisfaction showed the leakage was improved with non-significant difference between groups ( p > 0.05 ) . No complications were seen in any of the groups . CONCLUSION Even though the results showed non-significant decrease in pad 's weight among the three training groups , the pelvic floor muscle strength were increased in all groups Stress incontinence is the most prevalent form of female urinary incontinence and it affects approximately 5 % of younger women to nearly 50 % of elderly women . Women have traditionally been treated with pelvic floor muscle exercises alone or with the use of vaginal cones . A new treatment mode , vaginal balls , has been developed . The aim of this study was to compare pelvic floor muscle training with and without vaginal balls and to collect information on women 's subjective feelings about the two training modes . The study was carried out as a prospect i ve r and omized clinical trial . Thirty-seven women aged 25 - 65 were assigned either to a pelvic floor muscle training program or to a training program using weighted vaginal balls for 4 months . Treatment outcomes were assessed by a pad-test with a st and ardized bladder volume , vaginal palpation , and by women 's self-reported perceptions . The sense of coherence score was compared with the score for a normal population . Ninety-three percent of the women completed the study . Both training modes were effective in reducing urinary leakage : with vaginal balls ( P < 0.0001 ) and without ( P < 0.019 ) ; and increasing pelvic floor muscle strength : with vaginal balls ( P < 0.0039 ) and without ( P < 0.0002 ) . However , the reduction of urinary leakage after four months of exercise in the training group with vaginal balls was significantly better ( P < 0.03 ) than the results in the group training with pelvic floor muscle exercises alone . The study found the weighted vaginal balls to be a good alternative for training pelvic floor muscles in women with stress urinary incontinence AIMS Current management guidelines propose pelvic floor muscle training ( PFMT ) as first line treatment for female stress urinary incontinence ( SUI ) . The aim of this study is to compare the efficacy of group PFMT under intensive supervision to that of individual home therapy in women with SUI . MATERIAL AND METHODS Thirty women with clinical and urodynamic diagnosis of SUI were r and omized in two equal-number groups . Following a common demonstration course , Group A women received a detailed schedule for home training , while Group B in addition attended a weekly hospital group visit . At 12 weeks both groups were assessed for changes in subjective and objective outcomes . RESULTS Twenty-two women , ( 10 Group A , 12 Group B ) with a mean age of 47.3 years completed the study . Although significant ( P<0.05 ) improvements were noted in both groups in quality of life scores , number of incontinence episodes/week , 24-hr frequency , and endurance , repetitions and fast contractions upon vaginal assessment of the PFMs , comparative analysis at the end of the study demonstrated significantly better results for women in Group B , who also improved in daily pad usage , underwear wetting , modified Oxford grading of the PFMs and hold with cough . Consequently , significantly more women in Group B reported improvement in their continence ( 100 % vs. 20 % in Group A ) . CONCLUSIONS Group PFMT under intensive supervision produced significantly better improvements in primary and secondary outcomes in the short-term compared to individual , unsupervised home application of PFMT |
12,921 | 17,943,845 | There is strong evidence that the use of insoles does not prevent back pain .
There is limited evidence that insoles alleviate back pain or adversely shift the pain to the lower extremities .
There is strong evidence that insoles are not effective for the prevention of back pain . | BACKGROUND There is lack of theoretical and clinical knowledge of the use of insoles for prevention or treatment of back pain .
The high incidence of back pain and the popularity of shoe insoles call for a systematic review of this practice .
OBJECTIVES To determine the effectiveness of shoe insoles in the prevention and treatment of non-specific back pain compared to placebo , no intervention , or other interventions . | BACKGROUND Shock-absorbing and biomechanic shoe orthoses are frequently used in the prevention and treatment of back and lower extremity problems . One review concludes that the former is clinical ly effective in relation to prevention , whereas the latter has been tested in only 1 r and omized clinical trial , concluding that stress fractures could be prevented . OBJECTIVES To investigate if biomechanic shoe orthoses can prevent problems in the back and lower extremities and if reducing the number of days off-duty because of back or lower extremity problems is possible . DESIGN Prospect i ve , r and omized , controlled intervention trial . STUDY SUBJECTS One female and 145 male military conscripts ( aged 18 to 24 years ) , representing 25 % of all new conscripts in a Danish regiment . METHOD Health data were collected by question naires at initiation of the study and 3 months later . Custom-made biomechanic shoe orthoses to be worn in military boots were provided to all in the study group during the 3-month intervention period . No intervention was provided for the control group . Differences between the 2 groups were tested with the chi-square test , and statistical significance was accepted at P < .05 . Risk ratio ( RR ) , risk difference ( ARR ) , numbers needed to prevent ( NNP ) , and cost per successfully prevented case were calculated . OUTCOME VARIABLES Outcome variables included self-reported back and /or lower extremity problems ; specific problems in the back or knees or shin splints , Achilles tendonitis , sprained ankle , or other problems in the lower extremity ; number of subjects with at least 1 day off-duty because of back or lower extremity problems and total number of days off-duty within the first 3 months of military service because of back or lower extremity problems . RESULTS Results were significantly better in an actual-use analysis in the intervention group for total number of subjects with back or lower extremity problems ( RR 0.7 , ARR 19 % , NNP 5 , cost 98 US dollars ) ; number of subjects with shin splints ( RR 0.2 , ARR 19 % , NNP 5 , cost 101 US dollars ) ; number of off-duty days because of back or lower extremity problems ( RR 0.6 , ARR < 1 % , NNP 200 , cost 3750 US dollars ) . In an intention-to-treat analysis , a significant difference was found for only number of subjects with shin splints ( RR 0.3 , ARR 18 % , NNP 6 cost 105 US dollars ) , whereas a worst-case analysis revealed no significant differences between the study groups . CONCLUSIONS This study shows that it may be possible to prevent certain musculoskeletal problems in the back or lower extremities among military conscripts by using custom-made biomechanic shoe orthoses . However , because care-seeking for lower extremity problems is rare , using this method of prevention in military conscripts would be too costly . We also noted that the choice of statistical approach determined the outcome Study Design . R and omized controlled trial . Objectives . To determine if the use of custom shoe orthoses can lessen the incidence of weight bearing-induced back pain . Summary of Background Data . The scientific basis for the use of orthoses to prevent back pain is based principally on studies that show that shoe orthoses can attenuate the shock wave generated at heel strike . The repetitive impulsive loading that occurs because of this shock wave can cause wear of the mechanical structures of the back . Previous r and omized studies showed mixed results in preventing back pain , were not blinded , and used orthoses for only short periods of time . Methods . A total of 404 eligible new infantry recruits without a history of prior back pain were r and omly assigned to received either custom soft , semirigid biomechanical , or simple shoe inserts without supportive or shock absorbing qualities . Recruits were review ed biweekly by an orthopaedist for back signs and symptoms during the course of 14 weeks of basic training Results . The overall incidence of back pain was 14 % . By intention-to treat and per- protocol analyses , there was no statistically significant difference between the incidence of either subjective or objective back pain among the 3 treatment groups . Significantly more recruits who received soft custom orthoses finished training in their assigned orthoses ( 67.5 % ) than those who received semirigid biomechanical orthoses ( 45.5 % ) or simple shoe inserts ( 48.6 % ) , P = 0.001 . Conclusions . The results of this study do not support the use of orthoses , either custom soft or semirigid biomechanical , as prophylactic treatment for weight bearing-induced back pain . Custom soft orthoses had a higher utilization rate than the semirigid biomechanical or simple shoe inserts . The pretraining physical fitness and sports participation of recruits were not related to the incidence of weight bearing-induced back pain & NA ; Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies The prevalence and incidence of low back pain in general society is high . Workers whose job involves walking long distances have an even higher tendency to suffer from low back pain . A positive effect of insoles in reducing low back pain was found in professional sports players . This was not examined on people whose job involves walking long distances . In this double blind prospect i ve study we examined the effectiveness of insoles constructed in a computerized method to placebo insoles in 58 employees whose work entailed extensive walking and who suffered from low back pain . The evaluation was performed by the MILLION question naire , which is considered as a valid question naire for evaluation of low back pain . We calculated the differences of the pain intensity before and after the intervention , in the employees using the insoles manufactured by computer in comparison to the users of the placebo insoles . In each group , the analysis was performed in comparison to the baseline . A total of 81 % of the employees preferred the real insoles as effective and comfortable in comparison to 19 % of the users of the placebo insoles ( P<0.05 ) . The results of this study indicate a substantial improvement in the low back pain after the use of the true insoles . The average pain intensity according to the MILLION question naire before the use of the insoles was 5.46 . However , after the use of the real insoles and the placebo insoles , the average pain intensity decreased to 3.96 and 5.11 , respectively . The difference of the average pain intensity at the start of the study and after the use of the real insoles was significant : −1.49 ( P=0.0001 ) , whereas this difference after the use of the placebo insoles was not significant : −0.31 ( P=0.1189 ) . The reported severity of pain also decreased significantly : a level 5 pain and above was reported by 77 % of the subjects at the start of the study . After the use of the real insoles only 37.9 % of the subjects reported a similar degree of pain severity , and 50 % of the subjects did so after the use of the placebo insoles ( P < 0.05 ) . We did not find a link between low back pain and other variables such as gender , age , number of offspring , work seniority , smoking , previous use of insoles and previous medication . This study demonstrates that the low back pain decreased significantly after the use of real insoles compared to placebo ones Sedentary individuals , particularly new military recruits , who start a physical training program have a substantial risk of developing an overuse injury of the lower limb . In this study we investigated the effect of neoprene insoles on the incidence of overuse injuries during 9 weeks of basic military training . The experimental group consisted of 237 r and omly selected new recruits , while 1151 recruits were the control group . Insoles were given to the experimental group and compliance was monitored . A panel of doctors documented and classi fied all injuries occurring during the 9 week period . A total of 54 ( 22.8 % ) and 237 ( 31.9 % ) injuries were reported in the experimental and control groups , re spectively . In both groups , the majority of injuries were overuse ( experimental group , 90.7 % ; control group , 86.4 % ) . The mean weekly incidence of total overuse injuries and tibial stress syndrome was significantly lower ( P < 0.05 ) in the experimental group . The mean incidence of stress fractures was lower in the experimental group but not significantly so ( 0.05 < P < 0.1 ) . This study shows that the incidence of total overuse injuries and tibial stress syndrome during 9 weeks of basic military training can be reduced by wearing insoles A new approach to treating chronic low-back pain with custom-made foot orthoses was investigated . The Quebec Back Pain Disability Scale was used to objective ly assess the functional disability of 32 subjects at different times . Subjects in this prospect i ve study experienced more than twice the improvement in alleviation of pain , and for twice as long , compared with subjects in a study using traditional back-pain treatment . The authors believe that the findings of this study may provide a new method by which patients with chronic low-back pain can be evaluated and treated The purpose of this study was to assess the effect of viscoelastic shoe inserts on pain in nursing students . Students ( N = 100 ) were r and omly assigned to control and viscoelastic groups . The viscoelastic group used viscoelastic insoles in their work shoes for five weeks . A pain question naire was used to measure location and intensity of post-work pain . The question naire was administered as a pre-test and after five weeks . Post-test comparisons between groups indicated significant differences which were not present at pre-test . The viscoelastic group reported a significant peripheral shift in pain location from back to lower extremity ; the viscoelastic group also showed significant changes in duration of post-work pain and frequency of pain during the workday . The clinical efficacy of viscoelastic shoe inserts for modifying weight bearing-induced back pain is supported . Further clinical research into the therapeutic and prophylactic value of shock-attenuating shoe inserts for healthy as well as patient population s is advocated |
12,922 | 30,058,070 | Given the very low quality of the evidence , we are uncertain whether intermittent locking with heparin results in fewer occlusions than intermittent locking with NS .
Low- quality evidence suggests that heparin may have little or no effect on catheter patency .
Although we found no evidence of differences in safety ( sepsis , mortality , or haemorrhage ) , the combined trials are not powered to detect rare adverse events such as heparin-induced thrombocytopaenia | BACKGROUND Intermittent locking of central venous catheters ( CVCs ) is undertaken to help maintain their patency .
There are systematic variations in care : some practitioners use heparin ( at different concentrations ) , whilst others use 0.9 % NaCl ( normal saline ) .
This review looks at the effectiveness and safety of intermittent locking with heparin compared to 0.9 % NaCl to see if the evidence establishes whether one is better than the other .
This work is an up date of a review first published in 2014 .
OBJECTIVES To assess the effectiveness and safety of intermittent locking of CVCs with heparin versus normal saline ( NS ) in adults to prevent occlusion . | BACKGROUND Catheter-restricted antibiotic lock solutions were found to be effective in the prevention of catheter-related bacteremia ( CRB ) , but insufficient data are available about the ideal agent and dose . We hypothesized that a low concentration of gentamicin would be as effective as the high doses studied in the past . METHODS In this prospect i ve , open-labeled , r and omized , clinical trial of patients on long-term hemodialysis therapy , patients were r and omly assigned to administration of an antibiotic lock solution of gentamicin/citrate ( 4 mg/mL ) , minocycline/EDTA , or the control solution of heparin . Patients were followed up until the study end point of CRB was reached or a censoring event occurred . Interim data analysis was performed after 6 months to assess data safety ; efficacy was noted and the study was terminated early . RESULTS Sixty-two patients were enrolled into the study , evenly distributed in 3 arms , with data from 1 patient excluded from analysis . Seven of 20 patients in the heparin group ( 4.0 events/1,000 catheter days ) , 1 of 21 patients in the minocycline group ( 0.4 events/1,000 catheter days ) , and none of 20 patients in the gentamicin group developed bacteremia . Results were statistically significant by using 2-tailed Fisher exact test ; heparin versus gentamicin , P = 0.008 , and heparin versus minocycline , P = 0.020 . CONCLUSION Antibiotic lock solutions are superior to the st and ard heparin lock alone in the prevention of CRBs , and low-dose gentamicin solution has efficacy similar to that of greater concentrations used in previous studies BACKGROUND The role and dose of anticoagulants in thromboprophylaxis for patients with cancer receiving chemotherapy through central venous catheters ( CVCs ) is controversial . We therefore assessed whether warfarin reduces catheter-related thrombosis compared with no warfarin and whether the dose of warfarin determines the thromboprophylactic effect . METHODS In 68 clinical centres in the UK , we r and omly assigned 1590 patients aged at least 16 years with cancer who were receiving chemotherapy through CVCs to no warfarin , fixed-dose warfarin 1 mg per day , or dose-adjusted warfarin per day to maintain an international normalised ratio between 1.5 and 2.0 . Clinicians who were certain of the benefit of warfarin r and omly assigned patients to fixed-dose or dose-adjusted warfarin groups . The primary outcome was the rate of radiologically proven , symptomatic catheter-related thrombosis . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N 50312145 . FINDINGS Compared with no warfarin ( n=404 ) , warfarin ( n=408 ; 324 [ 79 % ] on fixed-dose and 84 [ 21 % ] on dose-adjusted ) did not reduce the rate of catheter-related thromboses ( 24 [ 6 % ] vs 24 [ 6 % ] ; relative risk 0.99 , 95 % CI 0.57 - 1.72 , p=0.98 ) . However , compared with fixed-dose warfarin ( n=471 ) , dose-adjusted warfarin ( n=473 ) was superior in the prevention of catheter-related thromboses ( 13 [ 3 % ] vs 34 [ 7 % ] ; 0.38 , 0.20 - 0.71 , p=0.002 ) . Major bleeding events were rare ; an excess was noted with warfarin compared with no warfarin ( 7 vs 1 , p=0.07 ) and with dose-adjusted warfarin compared with fixed-dose warfarin ( 16 vs 7 , p=0.09 ) . A combined endpoint of thromboses and major bleeding showed no difference between comparisons . We did not note a survival benefit in either comparison . INTERPRETATION The findings show that prophylactic warfarin compared with no warfarin is not associated with a reduction in symptomatic catheter-related or other thromboses in patients with cancer and therefore we should consider newer treatments . FUNDING Medical Research Council and Cancer Research UK PURPOSE The purpose of this study was to analyze the effectiveness of saline solution vs. heparinized-saline for maintenance of arterial lines and to detect changes in platelet and aPTT as physiological indexes . METHODS In this nonequivalent control group , non-synchronized , double-blind study the effects of heparinized and saline solution on the maintenance of arterial lines were compared . Fifty five patients received the heparinized solution and fifty nine patients received the saline solution . All patients who had surgery in K-university hospital between September and December 2011 were eligible for participation in the study . RESULTS There was no statistically significant difference between the saline and the heparin group in the maintenance time of the arterial lines or the number of irrigations . There was no statistically significant difference between the groups in changes in the number of platelets and aPTT for interaction between the groups and time intervals . CONCLUSION The results indicate that saline solution can be used as an irrigation solution for the maintenance of arterial lines of adult surgical patients , rather than heparinized-saline , in view of potential risk factors in the use of heparin INTRODUCTION AND AIMS The Subclavian vein has been traditionally the vein of choice for central venous catheterization by general surgeons . Alternative setting s for the introduction of totally implantable venous access devices ( TIVAD ) and the search for lower rates of morbidity led to the choice of other central veins . This study compares two different venous accesses , the subclavian ( SC ) versus the internal jugular ( IJ ) , in terms of early and late morbidity . PATIENTS AND METHODS This is a prospect i ve , non-r and omized , observational , uni-institutional ( tertiary cancer centre ) study . From March 2003 to March 2006 , 1231 TIVADs were placed ( 1201 patients ) , in an ambulatory operating room , under vital signs and EKG monitoring , using local anaesthesia and without perioperative radiological control . RESULTS Of the 1231 TIVAD , 617 were inserted via the SC and 614 via the IJ vein . The two groups ( SC vs. IJ ) were comparable as to general patient characteristics . Immediate complications were more frequent in the SC than in the IJ approach ( respectively , 5.0 % vs. 1.5 % ; p<0.001 ) ; Catheter malposition occurred in 2.3 % when using the SC vein and in 0.2 % for the IJ ( p=0.001 ) . Long term morbidity was also more frequent in the SC than in the IJ group ( respectively , 15.8 % , 87/551 , vs. 7.6 % , 39/512 ; p<0.001 ) . Venous thrombosis developed in 2.0 % of patients with an SC TIVAD as compared to 0.6 % with an IJ TIVAD ( p=0.044 ) . Catheter malfunction was significantly dependent on the vein used : SC - 9.4 % vs. IJ - 4.3 % ( p=0.001 ) . CONCLUSIONS Our results support the preferential use of the Internal Jugular vein for the insertion of TIVAD INTRODUCTION Catheter-related infection is associated with increased all-cause mortality and morbidity in hemodialysis patients . This study aim ed to evaluate an antimicrobial lock solution ( cloxacillin and heparin ) in temporary noncuffed double-lumen catheters for long-term intermittent hemodialysis as a method of preventing catheter-related infection . MATERIAL S AND METHODS Patients on hemodialysis with noncuffed temporary double lumen catheter were r and omly divided into 2 groups . Fifty patients received a solution containing cloxacillin , 100 mg/mL , plus heparin , 1000 IU/mL as a 2.5-mL solution instilled in each of catheter lumens after dialysis session . Another 50 patients received only heparin . They were allowed to dwell until the next session of dialysis . RESULTS One catheter-related bacteremia was observed in the antibiotic group whereas catheter-related bacteremia was observed in 8 of those who received heparin only . The rate of catheter-related bacteremia episodes were 0.5 per 1000 catheter-days in the antibiotic group versus 7.8 per 1000 catheter-days in the control group ( P = .02 ) . CONCLUSIONS In the present study , application of cloxacillin as antibiotic lock solution for dialysis catheters result ed in a considerable reduction in catheter-related bacteremia rate BACKGROUND Heparin is used as a flush solution for intravenous and intra-arterial lines , but has a number of drug interactions , as well as potentially serious side effects . METHODS We compared the function of arterial lines for both monitoring and blood sampling when flushed with either normal saline or saline containing heparin ( 1 unit/mL ) . Sixty-five patients were recruited at this mixed medical and surgical Level 2 intensive care unit . Patients were r and omised to receive either normal saline ( NS ) or heparinised saline ( HS ) ( 3 mL/hour as a continuous flush ) . Each patient 's nurse was asked to score the function of the line at the end of each nursing shift . RESULTS 35 patients were recruited in the NS group and 30 in the HS group . Mean study duration was 5.8 and 6.6 days for the NS and HS groups , respectively . The scores for the intravascular line for each patient were summed , and the percentage of the total possible score was calculated . Mean percentage scores were 83 % ( NS group ) and 82 % ( HS group ) . Comparison using the central limit theorem showed no difference between the groups at the 95 % confidence interval ( -6 % to 10 % ) . CONCLUSIONS Heparin as a continuous flush at 3 units/hour does not improve the function of arterial lines compared with a continuous normal-saline flush BACKGROUND AND OBJECTIVES Citrate 4 % has antithrombotic and antibacterial properties , which makes it a potentially superior alternative to heparin as an indwelling intraluminal locking agent . DESIGN , SETTING , PARTICIPANTS , AND MEASUREMENTS Sixty-one prevalent hemodialysis ( HD ) patients dialyzing with a tunneled cuffed HD catheter were r and omized in a pilot study to receive either heparin 5000 U/ml or citrate 4 % as a locking agent after HD . The primary outcomes were the development of catheter dysfunction ( defined as a blood pump speed < 250 ml/min or the use of tissue plasminogen activator ) and catheter-associated bacteremia . The secondary outcomes were the development of an exit-site infection or bleeding complications ( either local or systemic ) . RESULTS Citrate had comparable catheter dysfunction episodes to heparin ( 13/32 [ 41 % ] cases versus 12/29 [ 41 % ] cases , respectively ) . There were no differences in the development of catheter-associated bacteremia ( 2.2/1000 catheter days citrate versus 3.3/1000 catheter days heparin group ; P = 0.607 ) or exit-site infection ( 2.2/1000 catheter days for both groups ) . CONCLUSIONS The preliminary findings from our pilot study demonstrate that 4 % citrate is effective in maintaining catheter patency and does not appear to have any increased incidence of infections . Because citrate is significantly cheaper and has a more favorable side effect profile than heparin , it can be considered a potentially better locking agent in HD catheters Background Catheter-related bacteraemias ( CRBs ) contribute significantly to morbidity , mortality and health care costs in dialysis population s. Despite international guidelines recommending avoidance of catheters for haemodialysis access , hospital admissions for CRBs have doubled in the last decade . The primary aim of the study is to determine whether weekly instillation of 70 % ethanol prevents CRBs compared with st and ard heparin saline . Methods / design The study will follow a prospect i ve , open-label , r and omized controlled design . Inclusion criteria are adult patients with incident or prevalent tunneled intravenous dialysis catheters on three times weekly haemodialysis , with no current evidence of catheter infection and no personal , cultural or religious objection to ethanol use , who are on adequate contraception and are able to give informed consent . Patients will be r and omized 1:1 to receive 3 mL of intravenous- grade 70 % ethanol into each lumen of the catheter once a week and st and ard heparin locks for other dialysis days , or to receive heparin locks only . The primary outcome measure will be time to the first episode of CRB , which will be defined using st and ard objective criteria . Secondary outcomes will include adverse reactions , incidence of CRB caused by different pathogens , time to infection-related catheter removal , time to exit site infections and costs . Prospect i ve power calculations indicate that the study will have 80 % statistical power to detect a clinical ly significant increase in median infection-free survival from 200 days to 400 days if 56 patients are recruited into each arm . Discussion This investigator-initiated study has been design ed to provide evidence to help nephrologists reduce the incidence of CRBs in haemodialysis patients with tunnelled intravenous catheters . Trial Registration Australian New Zeal and Clinical Trials Registry Number : ABSTRACT The aim of the present study was to determine the efficacy of an antibiotic-lock technique in preventing endoluminal catheter-related infection with gram-positive bacteria in neutropenic patients with hematologic malignancies . Patients with nontunneled , multilumen central venous catheters were assigned in a r and omized , double-blinded manner to receive either 10 U of heparin per ml ( 57 patients ) or 10 U of heparin per ml and 25 μg of vancomycin per ml ( 60 patients ) , which were instilled in the catheter lumen and which were allowed to dwell in the catheter lumen for 1 h every 2 days . Insertion-site and hub swabs were taken twice weekly . The primary and secondary end points of the trial were significant colonization of the catheter hub and catheter-related bacteremia , respectively . Significant colonization of the catheter hub occurred in nine ( 15.8 % ) patients receiving heparin ( seven patients were colonized with Staphylococcus epidermidis , one patient was colonized with Staphylococcus capitis , and one patient was colonized withCorynebacterium sp. ) , whereas the catheter hubs of none of the patients receiving heparin and vancomycin were colonized ( P = 0.001 ) . Catheter-related bacteremia developed in four ( 7 % ) patients receiving heparin ( three patients had S. epidermidis bacteremia and one patient had S. capitisbacteremia ) , whereas none of the patients in the heparin and vancomycin group had catheter-related bacteremia ( P = 0.05 ) . The times to catheter hub colonization and to catheter-related bacteremia by the Kaplan-Meier method were longer in patients receiving heparin and vancomycin than in patients receiving heparin alone ( P = 0.004 and P = 0.06 , respectively ) . Our study shows that a solution containing heparin and vancomycin administered by using an antibiotic-lock technique effectively prevents catheter hub colonization with gram-positive bacteria and subsequent bacteremia during chemotherapy-induced neutropenia in patients with hematologic malignancy Purpose Whether an anticoagulant prophylaxis is needed for patients with cancer with a central venous catheter is a highly controversial subject . We design ed a study to compare different prophylactic strategies over 3 months of treatment . Methods We performed a phase III prospect i ve , open-label r and omized trial . After the insertion of a central venous access device , consecutive patients with planned chemotherapy for cancer were r and omized to no anticoagulant prophylaxis , low molecular weight heparin [ low molecular weight heparin ( LMWH ) ; with isocoagulation doses ] , or warfarin 1 mg/day . Treatments were given over the first 3 months . Doppler ultrasound and venographies were performed on days 1 and 90 , respectively , or sooner in case of clinical presumption of thrombosis . Results A total of 420 patients were r and omized , and 407 were evaluable . Forty-two catheter-related deep vein thrombosis ( DVT ) occurred ( 10.3 % ) , 20 in those with no anticoagulation , 8 in those receiving warfarin , and 14 in those receiving LMWH . Nine additional non-related catheter deep vein thrombosis ( CDVT ) occurred . Anticoagulation significantly reduced the incidence of catheter-related DVT ( p = 0.035 ) and catheter non-related DVT ( p = 0.007 ) , with no difference between warfarin and LMWH . Safety was good ( 3.4 % of attributable events ) but compliance with r and omized prophylaxis was lower than expected . Conclusions Prophylaxis showed a benefit regarding catheter-related and non-catheter-related DVT with no increase in serious side effects Background Occlusion of central venous catheters is one of the limiting factors in using them . Heparinized saline solution is the st and ard solution used for keeping the catheters open . Objectives This study aim ed to determine the effect of heparin saline solution and normal saline in maintenance of patency of central venous catheters . Patients and Methods This double-blind study was performed on 84 patients of intensive care unit who had central venous catheters . The patients were r and omly divided into two groups of heparin saline receivers and normal saline receivers . In the heparin group after each drug injection into the lumen , 3 mL of heparin saline solution was injected in the catheter as well . The other group only received 10 mL of normal saline instead . The catheters were examined for blood return and flushing every eight hours for 21 days . Data was analyzed using SPSS software version 20 and descriptive and analytic statistics were studied . Results There was no significant difference in the rate of flushing ( P = 0.872 ) and possibility of taking blood sample s from catheters ( P = 0.745 ) in the two groups of heparin and normal saline receivers . Furthermore , using heparin had no effect on prolonging the survival of catheters . Conclusions Considering possible side effects of heparin and the increase in treatment charges and the fact that using heparin did not have a significant effect on patency and survival of catheters in the studied patients , it is recommended to use normal saline solution to maintain the patency of central venous catheters The objective of this study was to assess the risk of bacteremia , estimate the cost and evaluate the quality of life by using a transparent dressing ( TD ) versus ( vs ) a dry gauze ( DG ) on the exit site of long term central I.V. catheters ( LTCC ) of hemodialysis patients . This 6-months preliminary study was conducted on 58 patients ( pts ) r and omized to receive DG replaced 3 times/week ( 29 pts ) or TD replaced every 7 days ( 29 pts ) . Data on patients , conditions of the exit site , local infection , bacteremia , quality of life and cost related to each type of dressing were collected . Two pts in the DG group experienced bacteremia related to their LTCC vs 1 pt in the group TD . A total of 7 ( DG ) vs 13 ( TD ) pts experienced skin condition changes at the catheter exit site . Some skin reactions , erythema and pruritus , did occur initially in the group TD and was due in part to insufficient drying time of the skin preparation solution . The estimated individual , weekly costs for using the DG was $ 7.60 vs $ 4.72 Canadian dollars for the TD . The SF-36 ™ scores did not show a significant difference between the 2 groups during the study ( 3.8 ( PCS ) , 6.4 ( MCS ) at study end ) . Although this study was statistically underpowered , it suggests that the incidence of bacteremia was not increased with the use of a TD . Moreover , the use of a TD allowed fewer dressing changes , lowered total treatment costs , with no observed unfavorable impact on the quality of life and without significant local complications of the exit site . Based on the positive results observed in this pilot study , further study is warranted to examine the cost effectiveness of long-term use of TD dressings on dialysis catheter exit sites OBJECTIVE To determine the frequency of central venous catheter-induced deep vein thrombosis of the femoral vein . DESIGN Prospect i ve , r and omized , controlled trial . SETTING Tertiary care center . PATIENTS Forty-five patients in a medical-surgical intensive care unit who required central venous catheterization . INTERVENTIONS Patients were r and omized to receive central venous catheterization in either upper ( subclavian or internal jugular veins ) or lower ( femoral vein ) catheterization sites . Lower extremity duplex ultrasound examinations were performed before central venous catheter placement , after removal of the catheter , and 7 days after catheter removal . Ultrasound examinations were reported as positive , nondiagnostic , or negative for deep vein thrombosis . MEASUREMENTS AND MAIN RESULTS Of the 21 patients r and omized to upper access sites , none developed positive or nondiagnostic duplex ultrasound examinations . Six ( 25 % ) of 24 patients r and omized to the femoral access site developed lower extremity deep vein thrombosis ( p = .02 ) . In addition , seven ( 29 % ) patients r and omized to the lower access site sustained non-diagnostic ultrasound examinations . A total of 13 ( 54 % ) of 24 patients from the lower access group developed abnormal ultrasound examinations ( p < .001 ) . Age , duration of catheterization , coagulation profile , deep vein thrombosis prophylaxis , and Acute Physiology and Chronic Health Evaluation II scores were similar between the upper and lower access groups . CONCLUSIONS Based on the data from this study , we concluded that femoral vein catheterization is associated with a 25 % frequency of lower extremity deep vein thrombosis compared with similar patients receiving subclavian or internal jugular vein catheters . The femoral vein remains an important emergency venous access route . Physicians inserting femoral vein catheters should be aware of the risk of lower extremity deep vein thrombosis and should consider performing lower extremity duplex ultrasound examinations on removal of femoral vein catheters Background and Purpose : Catheter-related bloodstream infection is the greatest threat to the safety of patients on hemodialysis . Catheter lock solutions containing heparin have been linked to an increased risk of hemorrhage and thrombocytopenia . Objectives : To ascertain the safety and efficacy for prevention of catheter-related bloodstream infection and catheter loss from patency failure of a novel catheter lock solution with antimicrobial and antithrombotic activity containing 0.24 M ( 7.0 % ) sodium citrate , 0.15 % methylene blue , 0.15 % methylparaben , and 0.015 % propylparaben ( C-MB-P ) , compared with heparin . Design : Multicenter , prospect i ve , r and omized , open-label trial with patients studied for up to 6 months . An independent clinical evaluation committee assessing trial outcomes was blinded to patients ' treatment assignments . Setting : Twenty-five outpatient hemodialysis units . Patients : Patients with end-stage renal disease receiving maintenance hemodialysis through a percutaneous cuffed and tunneled internal jugular hemodialysis catheters . Interventions : Participants ' catheters were locked between hemodialysis sessions with the C-MB-P lock solution or sterile saline containing 5000 units of unfractionated heparin ( control ) . Measurements and Main Results : We recorded and evaluated catheter-related bloodstream infections , catheter loss attributable to luminal thrombosis , and adverse events . A total of 407 patients participated in the trial ( 49,565 catheter days ) , 201 in the C-MB-P group and 206 in the heparin group . Patients in the two lock solution groups were comparable for risk factors predisposing to catheter-related bloodstream infection . Catheters locked with C-MB-P were significantly less likely to cause catheter-related bloodstream infection ( 0.24 vs. 0.82 per 1000 catheter days ; relative risk , 0.29 ; 95 % confidence interval , 0.12–0.70 ; p = .005 ) and were less likely to be lost because of patency failure ( 0 vs. 4 ; log rank , p = .04 ) . Conclusions : The novel C-MB-P lock solution is well tolerated , significantly reduces the risk of catheter-related bloodstream infection , and provides protection comparable to heparin against patency failure BACKGROUND The effectiveness of various solutions instilled into the central venous catheter lumens after each hemodialysis session ( catheter locking solutions ) to decrease the risk of catheter malfunction and bacteremia in patients undergoing hemodialysis is unknown . METHODS We r and omly assigned 225 patients undergoing long-term hemodialysis in whom a central venous catheter had been newly inserted to a catheter-locking regimen of heparin ( 5000 U per milliliter ) three times per week or recombinant tissue plasminogen activator ( rt-PA ) ( 1 mg in each lumen ) substituted for heparin at the midweek session ( with heparin used in the other two sessions ) . The primary outcome was catheter malfunction , and the secondary outcome was catheter-related bacteremia . The treatment period was 6 months ; treatment assignments were concealed from the patients , investigators , and trial personnel . RESULTS A catheter malfunction occurred in 40 of the 115 patients assigned to heparin only ( 34.8 % ) and 22 of the 110 patients assigned to rt-PA (20.0%)--an increase in the risk of catheter malfunction by a factor of almost 2 among patients treated with heparin only as compared with those treated with rt-PA once weekly ( hazard ratio , 1.91 ; 95 % confidence interval [ CI ] , 1.13 to 3.22 ; P = 0.02 ) . Catheter-related bacteremia occurred in 15 patients ( 13.0 % ) assigned to heparin only , as compared with 5 ( 4.5 % ) assigned to rt-PA ( corresponding to 1.37 and 0.40 episodes per 1000 patient-days in the heparin and rt-PA groups , respectively ; P = 0.02 ) . The risk of bacteremia from any cause was higher in the heparin group than in the rt-PA group by a factor of 3 ( hazard ratio , 3.30 ; 95 % CI , 1.18 to 9.22 ; P = 0.02 ) . The risk of adverse events , including bleeding , was similar in the two groups . CONCLUSIONS The use of rt-PA instead of heparin once weekly , as compared with the use of heparin three times a week , as a locking solution for central venous catheters significantly reduced the incidence of catheter malfunction and bacteremia . ( Current Controlled Trials number , IS RCT N35253449 . ) BACKGROUND Sodium citrate has antibacterial and anticoagulant properties that are confined to the catheter when used as a catheter lock . Studies of its use as a catheter lock have suggested its efficacy in preventing infection and bleeding complications compared with sodium heparin . STUDY DESIGN Open-label r and omized controlled trial of 2 catheter locks to examine the hypothesis that sodium citrate catheter locks will reduce catheter-related bacteremia and exit-site infection . SETTING S & PARTICIPANTS 232 consenting long-term hemodialysis patients in 4 satellite dialysis units to a large dialysis program with protocol ized treatment and targets . All patients were using twin-catheter single-lumen Tesio-Caths ( MedComp , Harleysville , PA ) . INTERVENTION 6 months ' use of 46.7 % sodium citrate ( citrate ) or 5 % heparin ( heparin ) locked postdialysis in the dead space of the central venous catheter . OUTCOMES & MEASUREMENTS Primary end point of catheter-related bacteremia and exit-site infection . Secondary end points of catheter thrombosis defined by the use of urokinase lock and infusion , new catheter insertion , catheter-related admission , blood transfusions , parenteral iron , and erythropoietin requirements . RESULTS Catheter-related bacteremia did not differ in the 2 groups , with an incidence of 0.7 events/1,000 catheter-days . There was no significant difference in rates of exit-site infection ( 0.7 versus 0.5 events/1,000 catheter-days ; P = 0.5 ) . The secondary end point of catheter thrombosis defined by the use of a urokinase lock was significantly more common in the citrate group , with an incidence of 8 versus 4.3/1,000 catheter-days ( P < 0.001 ) . Other secondary end points did not differ . Citrate treatment was curtailed compared with heparin because of a greater incidence of adverse events , with a mean treatment duration before withdrawal of 4.8 + /- 2.0 versus 5.7 + /- 1.2 months , respectively ( P < 0.001 ) . LIMITATIONS Low baseline catheter-related bacteremia and exit-site infection event rates may have underpowered this study . High adverse-event rates may have been related to high-concentration citrate that led to increased overspill and reduction in lock volume . This may also explain the increased rates of thrombosis in this group . CONCLUSION Widespread and long-term use of 46.7 % citrate catheter locks with Tesio-Cath access is not justified by this study BACKGROUND Hemato-oncology patients treated with intensive chemotherapy usually require the placement of a central venous catheter ( CVC ) . CVCs are frequently complicated by catheter-related central venous thrombosis ( CVT ) , which has been associated with an increased risk of pulmonary embolism and catheter-related infection . OBJECTIVES To determine the efficacy and safety of thromboprophylaxis with s.c . low-molecular-weight heparin ( nadroparin ) administered once daily in a r and omized placebo-controlled , double-blind trial in patients with hematologic malignancies . PATIENTS AND METHODS Consecutive patients with hematologic malignancies requiring intensive chemotherapy including autologous stem cell transplantation were eligible . The patients were r and omized to receive nadroparin 2850 antifactor Xa units once daily or placebo s.c . for 3 weeks . Venography was performed on day 21 after CVC insertion . Secondary outcomes were bleeding and catheter-related infection . RESULTS In total , 113 patients were r and omized to nadroparin or placebo , and 87 patients ( 77 % ) underwent venography . In total , 11 venographically proven catheter-related CVTs were diagnosed . The frequency of catheter-related CVT was not significantly different between study groups , namely four catheter-related CVTs in the placebo group [ 9 % ; 95 % CI : 0.002 - 0.16 ] vs. seven catheter-related CVTs in the nadroparin group ( 17 % ; 95 % CI : 0.06 - 0.28 ) . In addition , no difference in the incidence of catheter-related infection or bleeding was observed between the groups . CONCLUSION This study showed that the actual risk for catheter-related CVT in patients with hematologic malignancies is lower than suggested in earlier studies in cancer patients . Although prophylactic administration of nadroparin appeared to be safe in this group of patients with a high risk of bleeding , it can not be recommended for the prevention of catheter-related CVT or catheter-related infection in patients with hematologic malignancies BACKGROUND Heparin has been used for years as a locking solution in totally implantable venous access devices . Normal saline ( NS ) might be a safe alternative for heparin . However , evidence of non-inferiority of NS versus heparin is lacking . PATIENTS AND METHODS We r and omly allocated 802 cancer patients with a newly inserted port either to heparin lock ( 300 U/3 ml ) or to NS lock groups in a 1:1 assignment ratio . The primary outcome was the number of functional complications , which was defined as ' easy injection , impossible aspiration ' at port access . Secondary outcomes included all functional problems and catheter-related bacteraemia . We hypothesised that NS locks do not cause more functional problems and catheter-related bacteraemia than heparin locks . Non-inferiority is established if the upper limit of the confidence interval ( CI ) for the relative risk of NS versus heparin is < 1.4 . RESULTS Three hundred and eighty-two patients from the NS group and 383 from the heparin lock group were included in the analysis . The incidence rate of our primary outcome ( easy injection , impossible aspiration ) was 3.70 % ( 95 % CI 2.91%-4.69 % ) and 3.92 % ( 95 % CI 3.09%-4.96 % ) of accesses in the NS and heparin groups , respectively . The relative risk was 0.94 % ( 95 % CI 0.67%-1.32 % ) . Catheter-related bloodstream infection was 0.03 per 1000 catheter days in the NS group and 0.10 per 1000 catheter days in the heparin group . CONCLUSION NS is a safe and effective locking solution in implantable ports if combined with a strict protocol for device insertion and maintenance BACKGROUND Central venous catheters are frequently needed for the provision of haemodialysis , but their clinical usefulness is severely limited by infectious complications . The risk of such infections can be reduced by topical application of mupirocin to the exit sites of non-cuffed catheters or by the use of tunnelled , cuffed catheters . Whether mupirocin offers any additional protection against infection in patients with tunnelled , cuffed haemodialysis catheters has not been studied . METHODS An open-label , r and omized controlled trial was performed comparing the effect of thrice-weekly exit site application of mupirocin ( mupirocin group ) vs no ointment ( control group ) on infection rates and catheter survival in patients receiving haemodialysis via a newly inserted , tunnelled , cuffed central venous catheter . All patients were followed until catheter removal and were monitored for the development of exit site infections and catheter-associated bacteraemias . RESULTS Fifty patients were enrolled in the study . Both the mupirocin ( n=27 ) and control ( n=23 ) groups were similar at baseline with respect to demographic characteristics , comorbid illnesses and causes of renal failure . Compared with controls , mupirocin-treated patients experienced significantly fewer catheter-related bacteraemias ( 7 vs 35 % , P<0.01 ) and a longer time to first bacteraemia ( log rank score 8.68 , P<0.01 ) . The beneficial effect of mupirocin was entirely attributable to a reduction in staphylococcal infection ( log rank 10.69 , P=0.001 ) and was still observed when only patients without prior nasal Staphylococcus aureus carriage were included in the analysis ( log rank score 6.33 , P=0.01 ) . Median catheter survival was also significantly longer in the mupirocin group ( 108 vs 31 days , log rank score 5.9 , P<0.05 ) . Mupirocin use was not associated with any adverse patient effects or the induction of antimicrobial resistance . CONCLUSIONS Thrice-weekly application of mupirocin to tunnelled , cuffed haemodialysis catheter exit sites is associated with a marked reduction in line-related sepsis and a prolongation of catheter survival In this prospect i ve , r and omized study of 102 subjects with single-lumen peripherally inserted central catheters with positive pressure Luer-activated devices , 2 flushing solution groups were compared for their effect on occlusion rates . Of the 50 subjects r and omly assigned to the normal saline group , 3 ( 6 % ) experienced occlusions , all of whom were elderly women . There were no occlusions in the 52 subjects r and omly assigned to the heparinized saline group . Although the occlusion rate findings were not statistically significant , the charges associated with replacing a PICC because of occlusion are economically relevant . The annualized savings attributable to heparinized saline use are $ 22,891 BACKGROUND & AIMS Catheter-related bloodstream infections remain the major threat for Home Parenteral Nutrition programs . Taurolidine , a potent antimicrobial agent , holds promise as an effective catheter lock to prevent such infections . Aim of the present study was to compare taurolidine with heparin , the most frequently used lock , in this respect in these high-risk patients . METHODS Thirty patients from one referral centre for intestinal failure were enrolled after developing a catheter-related bloodstream infection . Following adequate treatment , either with or without a new access device ( tunneled catheter or subcutaneous port ) , these patients were r and omized to continue Home Parenteral Nutrition using heparin ( n = 14 ) or taurolidine ( n = 16 ) as catheter lock . RESULTS Whereas in controls 10 re-infections were observed , in the taurolidine group during 5370 catheter days only 1 re-infection occurred ( mean infection-free survival 175 ( 95 % CI 85 - 266 ; heparin ) versus 641 ( 95 % CI 556 - 727 ; taurolidine ) days ; log-rank p < 0.0001 ) . No side effects or catheter occlusions were reported in either group . Moreover , after crossing-over of 10 patients with infections on heparin to taurolidine , only 1 new infection was observed . CONCLUSION Taurolidine lock dramatically decreased catheter-related bloodstream infections when compared with heparin in this high-risk group of Home Parenteral Nutrition patients Objectives The objectives were to analyze the effectiveness of heparinized solution vs. saline solution for the maintenance of arterial catheters and to detect changes in the activated partial thromboplastin time ( aPTT ) and platelet count in the sample s extracted from both groups of arterial catheters . Design R and omized , double blind , placebo-controlled clinical trial . Setting Intensive Care Unit of a third-level hospital in Terrassa , Barcelona , Spain . Patients One hundred and thirty-three patients were included in the trial . The selection criteria were : adults , informed consent , not receiving either full-dose anticoagulant or fibrinolytic treatment , and no thrombocytopenia . Interventions Sixty-five patients received heparinized solution ( 1 IU/ml ) and 68 received saline solution . Measurements Arterial catheter functionality was compared in the groups every 8 h and at catheter removal . Patency , reliability of arterial pressure , and curve quality were used to evaluate the functionality of the catheters . Blood was drawn , discarding 7.5 ml , from the arterial catheter and from the venouscatheter simultaneously for coagulation tests . Results The median duration of catheters being in place was 5.1 days ( IQR = 8.1 ) in the heparin group , and 5.4 ( IQR = 7.3 ) in the saline group ( p = 0.7 ) . Kaplan – Meier curves showed no differences between groups ( p = 0.6 ) . The number of manipulations required to maintain the patency of the arterial catheters was 35 % vs. 40 % ( p = 0.5 ) . The heparin group had a significantly longer aPTT ( 2.1 ± 1.3 vs. 1.25 ± 0.3 , p = 0.001 ) . Conclusions The use of heparinized solution for arterial catheter maintenance doesnot appear to be justified . It did not increase the duration of the catheters , nor did it improve their functionality significantly . On the other h and , heparin Na altered aPTT significantly BACKGROUND We evaluated efficacy and safety of early and short-term prophylaxis with acenocumarine or dalteparin in the prevention of non-occlusive or occlusive central vein catheter-related thrombosis ( CVCrT ) . PATIENTS AND METHODS Consecutive cancer patients scheduled for chemotherapy r and omly received : acenocumarine 1 mg/day for 3 days before and 8 days after central vein catheter ( CVC ) insertion ; dalteparin 5000 IU 2 h before and daily for 8 days after CVC insertion ; no anticoagulant treatment ( NT ) . All patients underwent venography on days 8 and 30 , some of them on days 90 , 150 and 210 after CVC . RESULTS A total of 450 patients were r and omized , 348 underwent at least two venography . Both acenocumarine and dalteparin reduced venography-detected CVCrT rate [ 21.9 % acenocumarine versus 52.6 % NT , odds ratio ( OR ) 0.3 , P < 0.01 ; 40 % dalteparin versus 52.6 % NT , OR 0.6 , P = 0.05 ] . Acenocumarine was more effective than dalteparin ( OR 0.4 , P = 0.01 ) . The rate of occlusive CVCrT was not different in the three groups ( 0.9 % acenocumarine , 3.3 % dalteparin , 1.8 % NT ; P = 0.40 ) . Most CVCrTs ( 95.6 % ) were observed on day 8 after CVC insertion and were non-occlusive . CONCLUSIONS In this study of early and short-term prophylaxis , acenocumarine was more effective than dalteparin on non-occlusive and asymptomatic CVCrT events . The first days following CVC insertion represent the highest risk for The function of long term indwelling venous access devices is commonly perturbed by postinsertion catheter‐related complications ( CRC ) . In an effort to assess the patterns of CRC in our community accurately , a prospect i ve analysis of Groshong catheters in adult cancer patients was undertaken Heparin sodium 10 units/mL was compared with 0.9 % sodium chloride injection as a flush solution for indwelling intermittent i.v . devices , or i.v . locks ( IVLs ) , in a prospect i ve , r and omized , double-blind study . The heparin and 0.9 % sodium chloride injections were prepared in the pharmacy using aseptic technique . Most of the IVLs were inserted by an i.v . therapy team member . Each patient 's IVL site was evaluated for phlebitis and patency by one of three study nurses , and when a catheter was removed , its contents were flushed so that clots or fibrin str and s could be detected . Nurses also collected information regarding disease states , surgical procedures , medications administered , and how long each site lasted . A total of 173 sites were studied in 76 patients in the heparin group , and 131 sites were studied in 71 patients in the sodium chloride group . The groups were well matched , except that the sodium chloride group received more vancomycin and dextrose-containing i.v . solutions , while the heparin group received more penicillins . There was no significant difference in the incidence of phlebitis or lost patency between the groups . When locks through which vancomycin , penicillins , and dextrose-containing i.v . solutions were administered were excluded , there was still no significant difference between the groups . ( ABSTRACT TRUNCATED AT 250 WORDS INTRODUCTION Catheter-related infection ( CRI ) is a major cause of morbidity and mortality in patients receiving hemodialysis . Antibiotic locking of these catheters has been shown to increase both the success of systemic antibiotic treatment in line sepsis , and to reduce the incidence of sepsis . We have studied the use of gentamicin locking of catheters ( in combination with st and ard heparin rather than previously reported citrate ) to reduce CRI rates . Furthermore , we have investigated the effects of this strategy on epoetin requirements and vascular access function . METHODS Fifty patients were studied . Patients were r and omized to catheter-restricted filling with either st and ard heparin ( 5000 IU/mL ) alone , or gentamicin and heparin ( 5 mg/mL ) . Epoetin requirements and hemoglobin response were monitored over the study period . RESULTS The gentamicin-locked group suffered only one infective episode ( 0.3/1000 catheter days ) compared to 10 episodes in six patients in the heparin alone group ( 4/1000 catheter days , P= 0.02 ) . The isolated organisms were equally split between Staphylococcal species and coliforms . There were no statistically significant differences in delivered dialysis dose ( Kt/V ) or QA between the two groups . Use of antibiotic locking was associated with both a higher mean hemoglobin ( 10.1 + /-0.14 g/dL vs. 9.2 + /- 0.17 g/dL in the heparin group , P= 0.003 ) and a lower mean epoetin dose ( 9000 + /- 734 IU/week vs. 10790 + /-615 IU/week in the heparin group , P= 0.04 ) . CONCLUSION The practice of locking newly inserted tunneled central venous catheters with gentamicin and heparin is an effective strategy to reduce line sepsis rates , and is associated with beneficial effects on epoetin requirements Objective To evaluate the effects of heparin saline versus normal saline as locking solution for maintaining patency in peripheral venous catheters in Chinese patients . Methods This open-label , r and omized controlled study was conducted in two hepatobiliary surgery wards , where patients received identical treatments , at a tertiary referral hospital . Patients were r and omly divided into a normal saline group ( NS , 3 ml ) or a heparin saline group ( HS , 50 IU/ml , 3 ml ) for catheter sealing . Results The study enrolled 286 patients and 609 peripheral venous catheters were included in the analysis . The patients in the two groups had no local infections or catheter-related bloodstream infections . There were no significant differences between the two groups in terms of the rate of catheter obstruction , duration time , or the rates of phlebitis , infiltration , and accidental catheter removal . Conclusions No significant differences in the peripheral venous catheter sealing effects were observed between normal saline and heparin saline usage in Chinese patients OBJECTIVE To evaluate in vitro and in vivo the efficacy of covalent end point-attached heparin to single-lumen polyurethane central venous catheters in reducing microbial adherence and colonization . DESIGN In vitro study : A controlled bench study . In vivo study : A prospect i ve , r and omized , double-blind , clinical trial . SETTING Intensive care unit in a 1200-bed teaching hospital . INTERVENTIONS In vitro study : Adhesion of 17 radiolabeled clinical isolates of Staphylococci to catheters was examined in vitro . In vivo study : The outcome of heparinized and control catheters was compared in vivo in patients receiving long-term parenteral nutrition . Fifty-five adult patients were prospect ively , blindly r and omized to heparinized or control central venous catheters . The catheters , removed on clinical grounds , were analyzed with semiquantitative and quantitative cultures . Blood cultures were done at catheter removal . MEASUREMENTS AND MAIN RESULTS In vitro study : Coagulase-negative Staphylococci adhered less in vitro to heparinized catheters than to control catheters ( p < .05 ) . In vivo study : Among 32 central venous catheters , or patients who completed the study , catheter-associated bacteremia or fungemia was observed in five patients in the control group ( n = 19 ) and in no patient with a heparinized catheter ( n = 13 ) ( p = .047 ) . Four of 13 catheters in the heparin group were colonized compared with 14 of 19 in the control group ( p = .03 ) . Coagulase-negative Staphylococci were the most frequent microorganisms in both groups . The numbers of organisms found on colonized catheters were larger in the control group than in the heparin group . CONCLUSIONS Covalent end point surface heparinization appears to have a great impact on both in vitro and in vivo bacterial colonization of central venous catheters . Such heparinization can be a practical and economical approach to the prevention of catheter-associated bacteremia or fungemia BACKGROUND AND AIMS Peripheral intravenous nutrition ( PIVN ) delivered via a finebore midline offers a viable alternative to central venous feeding . The major complication is the onset of peripheral vein thrombophlebitis ( PVT ) . Feed additives such as heparin and hydrocortisone have been advocated in its prevention . Concern over the safety of heparin has prevented its widespread use ; this study examines its true benefit . METHODS A r and omised , double-blind trial comparing the addition of either , Heparin 1500 units or hydrocortisone 15 mg or a combination of the two to full intravenous nutrition ( IVN ) ( 2500 ml , 13 g of nitrogen , 1190 m0sm/k ) was performed . All feeds were delivered via a finebore midline inserted via an antecubital fossa vein . Feeding was terminated in the event of complication or cessation of intended nutritional support . RESULTS One hundred and twenty-three episodes of feeding occurred in 110 patients . The incidence of peripheral vein thrombosis was similar in each group ( Heparin 30 % ( 12/41 ) , hydrocortisone 33 % ( 14/42 ) , combination 31 % ( 13/41 ) chi(2 ) test P>0.05 ) . There was a significant difference in total catheter survival with the addition of heparin to the feeds , either alone ( 11 days ( SEM 1.79 ) or in combination with hydrocortisone ( 11.7 days ( SEM 1.39 ) compared with those receiving only hydrocortisone ( 6.9 days ( SEM 0.73 ) P=0.002 and 0.030 , respectively ) ) . CONCLUSION When intravenous feeds are delivered in to a peripheral vein via a fine-bore midline , the addition of heparin to the feed extends the total period of feeding attainable BACKGROUND : Chronic hemodialysis patients frequently require vascular access through central venous catheters ( CVCs ) . The most significant complication of these catheters is infection . This risk can be lowered by the use of an antibiotic-Heparin lock . This study focuses on hemodialysis patients using Tunneled-cuffed catheters ( TCC ) , to assess the rate of catheter-related infections ( CRI ) in catheter-restricted filling with Cefotaxime and Heparin in end stage renal disease patients . METHODS : A double-blind r and omized study was conducted to compare 5000 U/ml Heparin plus10 mg/ml cefotaxime ( CE/HS ) as catheter-lock solutions , with Heparin ( 5000 U/ml ) alone . A total of 30 patients with end-stage renal disease and different etiologies , were enrolled for chronic hemodialysis with permanent catheters from December 2009 to March 2010 . These patients were r and omly assigned to two groups of 15 members . Blood sample s were collected for culture , sensitivity , and colony count , from the catheter lumen and the peripheral vein . CRI was considered as the end point . RESULTS : The rate of CRI was significantly lower in the cefotaxime group versus control group ( p < 0.001 ) . No exit site infection was occurred in both groups . Infection-free survival rates at 180 days were 100 % for the CE/HS group , and 56 % for the HS group . CONCLUSIONS : Antibiotic lock therapy using cefotaxime reduces the risk of CRI in hemodialysis patients BACKGROUND Central venous catheters ( CVCs ) are used for vascular access in hemodialysis patients who have no alternative access or are awaiting placement or maturation of a permanent access . The major complications of CVCs are catheter-related bloodstream infection and clotting in the catheter lumen . STUDY DESIGN Parallel-group , r and omized , multicenter clinical trial , with patients blinded to study intervention . SETTING & PARTICIPANTS 16 free-st and ing dialysis facilities in Northern California belonging to a single provider . 303 adult maintenance hemodialysis patients who were using a tunneled cuffed CVC for vascular access . INTERVENTION The treatment group received an antibiotic lock containing gentamicin 320 μg/mL in 4 % sodium citrate , whereas the control group received the st and ard catheter lock containing heparin 1,000 U/mL. Both groups received triple-antibiotic ointment on the catheter exit site during dressing changes at each dialysis treatment . OUTCOMES Catheter-related bloodstream infection and catheter clotting . MEASUREMENTS Catheter-related bloodstream infection was defined as the occurrence of symptoms consistent with bacteremia together with positive blood culture results in the absence of another obvious source of infection . Catheter clotting was measured as the rate of thrombolytic agent use required to maintain adequate blood flow . A single patient could contribute more than one infection or clotting episode . RESULTS The rate of catheter-related bloodstream infection was 0.91 episodes/1,000 catheter-days in the control group and 0.28 episodes/1,000 catheter-days in the treatment group ( P = 0.003 ) . The time to the first episode of bacteremia was significantly delayed ( P = 0.005 ) . The rates of tissue plasminogen activator use were similar in the treatment and control groups : 2.36 versus 3.42 events/1,000 catheter-days , respectively ( P = 0.2 ) . LIMITATIONS The requirement for dialysis facility staff to prepare the treatment intervention prevented a completely blinded study . CONCLUSION Gentamicin 320 μg/mL in 4 % sodium citrate used as a routine catheter lock in CVCs in patients on maintenance hemodialysis therapy markedly decreases the incidence of catheter-related bloodstream infection and is as effective as heparin 1,000 U/mL in preventing catheter clotting Objective : To compare heparin ( 3 mL , 10 units/mL ) and 0.9 % sodium chloride ( NaCl , 10 mL ) flush solutions with respect to central venous catheter lumen patency . Design : Single-center , r and omized , open label trial . Setting : Medical intensive care unit and Surgical/Burn/Trauma intensive care unit at Barnes-Jewish Hospital , St. Louis , MO . Patients : Three hundred forty-one patients with multilumen central venous catheters . Patients with at least one lumen with a minimum of two flushes were included in the analysis . Interventions : Patients were r and omly assigned within 12 hrs of central venous catheter insertion to receive either heparin or 0.9 % sodium chloride flush . Measurements and Main Results : The primary outcome was lumen nonpatency . Secondary outcomes included the rates of loss of blood return , inability to infuse or flush through the lumen ( flush failure ) , heparin-induced thrombocytopenia , and catheter-related blood stream infection . Assessment for patency was performed every 8 hrs in lumens without continuous infusions for the duration of catheter placement or discharge from intensive care unit . Three hundred twenty-six central venous catheters were studied yielding 709 lumens for analysis . The nonpatency rate was 3.8 % in the heparin group ( n = 314 ) and 6.3 % in the 0.9 % sodium chloride group ( n = 395 ) ( relative risk 1.66 , 95 % confidence interval 0.86–3.22 , p = .136 ) . The Kaplan-Meier analysis for time to first patency loss was not significantly different ( log rank = 0.093 ) between groups . The rates of loss of blood return and flush failure were similar between the heparin and 0.9 % sodium chloride groups . Pressure-injectable central venous catheters had significantly greater rates of nonpatency ( 10.6 % vs. 4.3 % , p = .001 ) and loss of blood return ( 37.0 % vs. 18.8 % , p < .001 ) compared to nonpressure-injectable catheters . The frequencies of heparin-induced thrombocytopenia and catheter-related blood stream infection were similar between groups . Conclusion : 0.9 % sodium chloride and heparin flushing solutions have similar rates of lumen nonpatency . Given potential safety concerns with the use of heparin , 0.9 % sodium chloride may be the preferred flushing solution for short-term use central venous catheter maintenance AIM The aim of this study was to evaluate the effect of heparin versus saline as flush solution for maintaining patency in peripheral intravenous locks in neonates and to investigate whether other variables influence the longevity of intravenous locks . BACKGROUND Heparin is usually used as a regular flush solution to prevent occlusion of peripheral intravenous locks in neonates . There is no clear recommendation using heparin or saline flushing peripheral intravenous locks in neonates . The disadvantage of heparin can not be ignored , especially in this patient group . METHODS In a double blind prospect i ve r and omized study , neonates ( gestational age > 27 weeks ) with intravenous locks were r and omly assigned to receive heparin or saline as a flush solution in a 21-month period ( 2002 - 2004 ) . The main outcome was the duration of patency . RESULTS Eighty-eight neonates were included . No statistically significant difference was found in patency of peripheral intravenous locks flushed with 0.7 mL heparin ( 10 units/mL ) ( N = 42 , median 56 hours ) or 0.7 mL saline ( N = 46 , median 61 hours ) . When the analysis was confined to removed locks because of non-elective events , no statistically significant difference was found in duration of patency ( P = 0.27 ) . CONCLUSION As no difference in patency could be established , using saline as a flush solution is preferable to heparin in peripheral intravenous locks in neonates , given the greater likelihood of complications associated with heparin . Although these data are more than 5 years old , the relevance of the outcome is still important for the clinical practice because of the potential adverse effects of heparin in these vulnerable infants BACKGROUND Cancer patients receiving chemotherapy experience thromboembolic complications associated with the use of long-term indwelling central venous catheters ( CVCs ) . This prospect i ve , double-blind , placebo-controlled , multicenter study evaluated whether prophylactic treatment with a low molecular weight heparin could prevent clinical ly relevant catheter-related thrombosis . PATIENTS AND METHODS Patients with cancer undergoing chemotherapy for at least 12 weeks ( n=439 ) were r and omly assigned , in a 2:1 ratio , to receive either dalteparin ( 5000 IU ) or placebo , by subcutaneous injection , once daily for 16 weeks . Patients underwent upper extremity evaluation with either venography or ultrasound at the time of a suspected catheter-related complication ( CRC ) or upon completion of study medication . The primary end point , as determined by a blinded adjudication committee , was the occurrence of a CRC , defined as the first occurrence of any one of the following : clinical ly relevant catheter-related thrombosis that was symptomatic or that required anticoagulant or fibrinolytic therapy ; catheter-related clinical ly relevant pulmonary embolism ; or catheter obstruction requiring catheter removal . RESULTS There was no significant difference in the frequency of CRCs between the dalteparin arm ( 3.7 % ) and the placebo arm ( 3.4 % ; P=0.88 ) , corresponding to a relative risk of 1.0883 ( 95 % confidence interval 0.37 - 3.19 ) . No difference in the time to CRC was observed between the two arms ( P=0.83 ) . There was no significant difference between the dalteparin and placebo groups in terms of major bleeding ( 1 versus 0 ) or overall safety . CONCLUSIONS Dalteparin prophylaxis did not reduce the frequency of thromboembolic complications after CVC implantation in cancer patients . Dalteparin was demonstrated to be safe over 16 weeks of treatment in these patients OBJECTIVES The aim of this study was to prospect ively evaluate the use of intraluminal ethanol for the prevention of catheter-associated bloodstream infection ( CABSI ) in immunosuppressed haematology patients . PATIENTS AND METHODS Patients receiving chemotherapy for haematological malignancy or haematopoietic cell transplantation were r and omized in a double-blinded manner to receive either intraluminal 70 % ethanol/water or heparinized saline locks on a daily basis throughout a prophylactic treatment period . The primary endpoint was an episode of CABSI ( defined as ' bacteraemia in a febrile patient with a central venous catheter that was in use within the preceding 48 h and with no other identified focus of infection ' ) . The trial was registered with the Australian Clinical Trials Register : number ACTRN012605000383662 . RESULTS There were 34 and 30 prophylactic treatment periods in the ethanol and control groups , respectively . CABSI occurred in 3 ( 9 % , 0.60/100 catheter-days ) and 11 ( 37 % , 3.11/100 catheter-days ) prophylactic treatment periods in the ethanol and control groups , respectively ( OR = 0.18 , 95 % CI 0.05 - 0.65 , P = 0.008 ) . Eleven ( 32 % ) and 5 ( 17 % ) patients in the ethanol and control groups , respectively , remained afebrile throughout the prophylactic treatment ( P = 0.18 ) . CONCLUSIONS The daily administration of ethanol locks into lumens of central venous catheters effectively reduces the incidence of CABSI As professionals , we want to use the best treatments ; as patients , we want to be given them . Knowing whether an intervention works ( or does not work ) is fundamental to clinical decision making . However , clinical decision making involves more than simply taking published results of research directly to the bedside . Physicians need to consider how similar their patients are to those in the published studies , to take the values and preferences of their patients into account , and to consider their own experience with a given test or treatment . Evidence from clinical research is becoming increasingly important in medical- practice decisions as more and better evidence is published . But when is the evidence strong enough to justify changing a practice ? Individual studies that involve only small numbers of patients may have results that are distorted by the r and om play of chance and thus lead to less than optimal decisions . As is clear from other papers in this series , systematic review s identify , critically appraise , and review all the relevant studies on a clinical question and are more likely to give a valid answer . They use explicit methods and quality st and ards to reduce bias . Their results are the closest we can come to reaching the truth given our current state of knowledge . The questions about an intervention that a systematic review should answer are the following : 1 . Does it work ? 2 . If it works , how well does it work in general and compared with placebo , no treatment , or other interventions that are currently in use ? 3 . Is it safe ? 4 . Will it be safe and effective for my patients ? Whereas the critical appraisal and qualitative synthesis provided by review articles can be interpreted directly , the numerical products of quantitative review s can be more difficult to underst and and apply in daily clinical practice . This paper provides guidance on how to interpret the numerical and statistical results of systematic review s , translate these results into more underst and able terms , and apply them directly to individual patients . Many of these principles can also be used to interpret the numerical results of individual clinical studies . They are particularly relevant to systematic review s , however , because such review s contain more information than do primary studies and often exert greater influence than do individual studies . Making Sense of the Numerical Results of Clinical Studies Although the results of clinical studies can be expressed in intuitively meaningful ways , such results do not always easily translate into clinical decision making . For example , results are frequently expressed in terms of risk , which is an expression of the frequency of a given outcome . ( Risks are probabilities , which can vary between 0.0 and 1.0 . A probability of 0.0 means that the event will never happen , and a probability of 1.0 means that it always happens . ) Consider a hypothetical study of the recurrence of migraine headaches in a control group receiving placebo and a treatment group receiving a new antimigraine preparation , drug M ( a secondary prevention trial ) . Suppose that at the end of the trial , migraines recurred in 30 % of the control group ( the risk for recurrence was 0.30 ) but in only 5 % of the drug M group ( risk of 0.05 ) ( Table 1 ) . Table 1 . Numerical Expression of Hypothetical Clinical Trial Results The outcomes of the study are clear enough for the two groups when they are examined separately . But clinicians and patients are more interested in the comparative results , that is , the outcome in one group relative to the outcome in the other group . This overall ( comparative ) result can be expressed in various ways . For example , the relative risk , which is the risk in the treatment group relative to that in the control group , is simply the ratio of the risks in the two groups . In other words , relative risk is the risk in the treatment group divided by that in the control group , 0.05 0.30 , or 0.17 . The comparison can also be expressed as the reduction in relative risk , which is the ratio between the decrease in risk ( in the treatment group ) and the risk in the control group , 0.25 0.30 , or 0.83 ( Table 1 ) . ( The relative risk reduction can also be calculated as 1 relative risk ) . Although the clinical meaning of relative risk ( and relative risk reduction ) is reasonably clear , relative risk has the distinct disadvantage that a given value ( for example , 0.17 ) is the same whether the risk with treatment decreases from 0.80 to 0.14 , from 0.30 to 0.05 , from 0.001 to 0.00017 , and so forth . The clinical implication s of these changes clearly differ from one another enormously and depend on the specific disease and intervention . An important alternate expression of comparative results , therefore , is the absolute risk reduction . Absolute risk reduction is determined by subtracting the risk in one group from the risk in the other ( for example , the risk in the treatment group is subtracted from the risk in the placebo group ) . In the case of our migraine study , the absolute risk reduction would be 0.30 0.05 , which equals 0.25 , or 25 percentage points . In contrast , for a study in which the risk decreased from 0.001 to 0.00017 , the absolute risk reduction would be only 0.00083 , or 0.083 percentage points , which is a trivial change in comparison ( Table 1 ) . This arithmetic emphasizes the difficulty of expressing the results of clinical studies in meaningful ways . Relative risk and relative risk reduction clearly give a quantitative sense of the effects of an intervention in proportional terms but provide no clue about the size of an effect on an absolute scale . In contrast , although it tells less about proportional effects , absolute risk says a great deal about whether an effect is likely to be clinical ly meaningful . Despite this benefit , even absolute risk is problematic because it is a dimensionless , abstract number ; that is , it lacks a direct connection with the clinical situation in which the patient and physician exist . However , another way of expressing clinical research results can provide that clinical link : the number needed to treat ( NNT ) . Number Needed To Treat The NNT for a given therapy is simply the reciprocal of the absolute risk reduction for that treatment [ 1 , 2 ] . In the case of our hypothetical migraine study ( in which risk decreased from 0.30 without treatment with drug M to 0.05 with treatment with drug M , for a relative risk of 0.17 , a relative risk reduction of 0.83 , and an absolute risk reduction of 0.25 ) , the NNT would be 1 0.25 , or 4 . In concrete clinical terms , an NNT of 4 means that you would need to treat four patients with drug M to prevent migraine from recurring in one patient . To emphasize the difference between the concepts embodied in NNT and relative risk , recall the various situations mentioned above , in all of which the relative risk was 0.17 but in which the absolute risk decreased from 0.80 to 0.14 in one case and from 0.001 to 0.00017 in another . Note that the corresponding NNTs in these two other cases are 1.5 and 1204 , respectively : that is , you would need to treat 1.5 and 1204 patients to obtain a therapeutic result in these two situations compared with 4 patients with drug M ( Table 1 ) . The NNT can be calculated easily and kept as a single numerical reminder of the effectiveness ( or , as we will see , the potential for harm ) of a particular therapy . As we suggested , the NNT has the crucial advantage of direct applicability to clinical practice because it shows the effort that is required to achieve a particular therapeutic target . The NNT has the additional advantage that it can be applied to any beneficial outcome or any adverse event ( when it becomes the number needed to harm [ NNH ] ) . The concept of NNT always refers to a comparison group ( in which patients receive placebo , no treatment , or some other treatment ) , a particular treatment outcome , and a defined period of treatment . In other words , the NNT is the number of patients that you will need to treat with drug or treatment A to achieve an improvement in outcome compared with drug or treatment B for a treatment period of C weeks ( or other unit of time ) . To be fully specified , NNT and NNH must always specify the comparator , the therapeutic outcome , and the duration of treatment that is necessary to achieve the outcome . Important Qualities of the Number Needed To Treat The NNT is treatment specific . It describes the difference between treatment and control in achieving a particular clinical outcome . Table 2 shows NNTs from a selection of systematic review s and large r and omized , controlled trials . Table 2 . Numbers Needed To Treat from Systematic Review s and R and omized , Controlled Trials A very small NNT ( that is , one that approaches 1 ) means that a favorable outcome occurs in nearly every patient who receives the treatment and in few patients in a comparison group . Although NNTs close to 1 are theoretically possible , they are almost never found in practice . However , small NNTs do occur in some therapeutic trials , such as those comparing antibiotics with placebo in the eradication of Helicobacter pylori infection or those examining the use of insecticide for head lice ( Table 2 ) . An NNT of 2 or 3 indicates that a treatment is quite effective . In contrast , such prophylactic interventions as adding aspirin to streptokinase to reduce 5-week vascular mortality rates after myocardial infa rct ion may have NNTs as high as 20 to 40 and still be considered clinical ly effective . Limitations of the Number Needed To Treat Although NNTs are powerful instruments for interpreting clinical effects , they also have important limitations . First , an NNT is generally expressed as a single number , which is known as its point estimate . As with all experimental measurements , however , the true value of the NNT can be higher or lower than the point estimate determined through clinical studies . The 95 % CIs of the NNT are useful in this regard because they provide an indication that Background Tunnelled central venous dialysis catheter use is significantly limited by the occurrence of catheter-related infections . This r and omised controlled trial assessed the efficacy of a 48 hour 70 % ethanol lock vs heparin locks in prolonging the time to the first episode of catheter related blood stream infection ( CRBSI ) . Methods Patients undergoing haemodialysis ( HD ) via a tunnelled catheter were r and omised 1:1 to once per week ethanol locks ( with two heparin locks between other dialysis sessions ) vs thrice per week heparin locks . Results Observed catheter days in the heparin ( n=24 ) and ethanol ( n=25 ) groups were 1814 and 3614 respectively . CRBSI occurred at a rate of 0.85 vs. 0.28 per 1000 catheter days in the heparin vs ethanol group by intention to treat analysis ( incident rate ratio ( IRR ) for ethanol vs. heparin 0.17 ; 95%CI 0.02 - 1.63 ; p=0.12 ) . Flow issues requiring catheter removal occurred at a rate of 1.6 vs 1.4 per 1000 catheter days in the heparin and ethanol groups respectively ( IRR 0.85 ; 95 % CI 0.20 - 3.5 p = 0.82 ( for ethanol vs heparin ) . Conclusions Catheter survival and catheter-related blood stream infection were not significantly different but there was a trend towards a reduced rate of infection in the ethanol group . This study establishes proof of concept and will inform an adequately powered multicentre trial to definitively examine the efficacy and safety of ethanol locks as an alternative to current therapies used in the prevention of catheter-associated blood stream infections in patients dialysing with tunnelled catheters . Trial Registration Australian New Zeal and Clinical Trials Registry Purpose There is an increasing number of patients being dialyzed with permanent catheters ( PC ) . In the majority of cases , heparin is used to maintain PC patency . This practice causes clotting disturbances due to heparin leakage and may predispose the patient to bleeding episodes . It has not been well studied whether lowering heparin concentration for canal locking decreases short-term bleeding complications after PC placement . Methods This was a prospect i ve single-center r and omized open-label trial conducted in hemodialyzed patients undergoing PC insertion . Low concentration of heparin ( LCH ) 2,500 IU/ml versus high concentration of heparin ( HCH ) 5,000 IU/ml was r and omly used for catheter lumens locking . The primary endpoint was the occurrence of bleeding within 24 h after catheter placement . The effects of clinical and laboratory data on bleeding events were analyzed as secondary endpoints . Results Seventy-five patients ( 37 in LCH ) were enrolled in the study . Only in the HCH group we found a significant prolongation of activated partial thromboplastin time ( APTT ) 2 h after PC placement ( p < 0.001 ) . There was a higher number of bleeding episodes in the HCH group ( n = 16 ; 42.1 % ) than in the LCH group ( n = 7 ; 18.9 % ) ( χ2 = 4.74 ; p = 0.029 ) . In univariate analysis , assignment to HCH , baseline APTT , use of low molecular weight heparin , and femoral localization were associated with bleeding events . In multivariate analysis , the use of HCH ( odds ratio [ OR ] 3.64 ; 95 % confidence interval [ 95 % CI ] 1.10–12.05 ) and baseline APTT ( OR 1.12 ; 95 % CI 1.002–1.250 ) predicted bleeding after PC insertion . Conclusion LCH used for canals locking decreases bleeding events in the first 24 hours after permanent catheter placement , compared to HCH Tunneled catheters are widely used for the provision of hemodialysis . Long-term catheter survival is limited by tunneled catheter-related infections ( CRI ) . This study assesses the efficacy of catheter-restricted filling with gentamicin and citrate in preventing CRI in hemodialysis patients . A double-blind r and omized study was conducted to compare heparin ( 5000 U/ml ) with gentamicin/citrate ( 40 mg/ml and 3.13 % citrate ; ratio 2:1 ) as catheter-lock solutions . A total of 112 tunneled catheters in 83 patients were enrolled at the time of catheter insertion for commencement or maintenance of hemodialysis . The primary end point was CRI . Catheter malfunction , defined as blood flow rate of < 200 ml/min for three consecutive dialyses and /or the use of urokinase , was also assessed as a secondary end point . Infection rates per 100 catheter-days were 0.03 in the gentamicin group versus 0.42 in the heparin group ( P = 0.003 ) . Kaplan-Meier survival analyses showed mean infection-free catheter survival of 282 d ( 95 % CI , 272 to 293 d ) in the gentamicin group versus 181 d ( 95 % CI , 124 to 237 d ) in the heparin group ( log rank , 9.58 ; P = 0.002 ) . Cox regression analyses showed a relative risk for infection-free catheter survival of 0.10 ( 95 % CI , 0.01 to 0.92 ) in the gentamicin group when adjusted for gender , race , diabetes mellitus , catheter malfunction , and hemoglobin ( P = 0.042 ) . The incidence of catheter malfunction was not significantly different between groups . Predialysis gentamicin levels were significantly higher in patients r and omized to gentamicin ( gentamicin/citrate : median 2.8 mg/L [ range , 0.6 to 3.5 mg/L ] , n = 5 ; heparin : median < 0.2 mg/L [ range < 0.2 to 0.2 mg/L ] , n = 5 ; P = 0.008 ) . Tunneled hemodialysis catheter-restricted filling with gentamicin and citrate is a highly effective strategy for prevention of CRI . Although citrate as a catheter-lock solution provides adequate anticoagulation for the interdialytic period , gentamicin levels suggest significant risk for chronic aminoglycoside exposure and associated ototoxicity . Before this technique is adopted , these preliminary observations warrant replication in future studies that will examine the efficacy and safety of lower doses of gentamicin or alternative agents with a reduced potential for toxicity OBJECTIVES The use of an antibiotic lock ( AB-lock ) for the treatment of catheter-related bloodstream infection ( CRBSI ) has been suggested , but r and omized trials have never been performed . METHODS A r and omized , blinded , multicentre trial was set up to compare an AB-lock-containing vancomycin for Gram-positive or ceftazidime for Gram-negative bacteria-with placebo , in addition to parenteral AB therapy . We included only CRBSI from a long-term intravascular device ( LTID ) whether tunnelled or totally implanted . RESULTS During 30 months , 174 patients with an LTID and bacteraemia were evaluated , of whom 85 had a CRBSI . Forty-six patients were included . Frequent reasons for exclusion were : catheter not vacant for > 8 - 12 h/day for the AB-lock ( n = 10 ) ; yeast infection or mixed Gram-positive/negative infections ( n = 13 ) ; catheter removal preferred by the treating physician ( n = 7 ) ; and CRBSI < 14 days after insertion or pocket/tunnel infection ( n = 10 ) . Forty-four patients met the criteria for modified intention-to-treat analysis . The primary endpoint was failure to cure the CRBSI or relapse with the same strain . On study day 180 by Kaplan-Meier analysis , this occurred in 33 % ( seven of 21 ) in the AB-lock arm and in 57 % ( 13 of 23 ) in the placebo arm ( hazard ratio 0.55 , P = 0.10 ) . A relapse with the same strain occurred in 9/23 with the placebo and 3/21 with the AB-lock ( P = 0.06 ) . CONCLUSION Future studies should take into account the barriers to the use of AB-lock observed in this study . Most importantly , shorter lock dwell times and broader spectrum locks ( e.g. antiseptic ) should be investigated to target a larger patient population Heparin anticoagulation during cardiovascular surgical procedures remains poorly investigated and understood . The objective of this investigation was to assess the effectiveness of three methods of heparin administration . Heparin sulfate ( 75 IU/kg ) administered to patients undergoing aortoiliac surgery was r and omised to one of three methods : Group I ( n = 9 ) heparin was injected into a central venous line 5 minutes before infrarenal aortic clamping ; Group II ( n = 9 ) heparin was injected into the distal aneurysm immediately after infrarenal aortic clamping ; and Group III ( n = 8) heparin was injected into a central venous line immediately after infrarenal aortic clamping . Blood sample s were analysed for anticoagulant activity from both the upper and lower extremities at 5 , 15 , 30 , 60 , and 120 minutes after heparin administration . Anticoagulation , as measured by aPTT , antifactor Xa levels , and ACT , was achieved in all three groups by 5 minutes , but initially with lower heparin activity ( measured as antifactor Xa ) in the upper extremity ( Group II ) and lower extremity ( Group III ) , respectively . These differences were also evident in ACT and aPTT determinations . Intravenous heparin administration prior to aortic cross-clamping achieves excellent anticoagulation ( anti-factor Xa approximately 1 U/ml ) in both upper and lower extremities after 5 minutes . With regional administration , rapid heparin redistribution occurs , but it takes longer to achieve the same level of anticoagulation distant from the site of administration . Nevertheless , from a practical perspective the method of administration does not appear to have a great influence on the eventual achievement of adequate anticoagulation BACKGROUND Central venous catheters ( CVCs ) continue to be used at a high rate for dialysis access and are frequently complicated by thrombus-related malfunction . Prophylactic locking with an anticoagulant , such as heparin , has become st and ard practice despite its associated risks . Trisodium citrate ( citrate ) 4 % is an alternative catheter locking anticoagulant . METHODS The objective was to prospect ively study the clinical effectiveness , safety and cost of citrate 4 % vs heparin locking by comparing rates of CVC exchanges , thrombolytic use ( TPA ) and access-associated hospitalizations during two study periods : heparin period ( HP ) ( 1 June 2003 - 15 February 2004 ) and Citrate Period ( CP ) 15 March-15 November 2004 . Incident catheters evaluated did not overlap the two periods . RESULTS There were 176 CVC in 121 patients ( HP ) and 177 CVC in 129 patients ( CP ) . The event rates in incident CVC were : CVC exchange 2.98/1000 days ( HP ) vs 1.65/1000 days ( CP ) ( P = 0.01 ) ; TPA use 5.49/1000 ( HP ) vs 3.3/1000 days ( CP ) ( P = 0.002 ) ; hospitalizations 0.59/1000 days ( HP ) vs 0.28/1000 days ( CP ) ( P = 0.49 ) . There was a longer time from catheter insertion to requiring CVC exchange ( P = 0.04 ) and TPA ( P = 0.006 ) in the citrate compared with the heparin lock group . Citrate locking costs less than heparin locking but a formal economic analysis including indirect costs was not done . CONCLUSION Citrate 4 % has equivalent or better outcomes with regards to catheter exchange , TPA use and access-related hospitalizations compared with heparin locking . It is a safe and less expensive alternative . R and omized trials comparing these anticoagulants with a control group would definitively determine the optimal haemodialysis catheter locking solution To assess whether adding low-dose heparin to the infusate of patients receiving parenteral nutrition reduced the incidence of septic complications related to the central venous catheter , 80 consecutive patients requiring intravenous feeding were studied . Half of these patients received heparin 1 unit/ml of infusate , while in the remaining 40 ( controls ) an equal volume of physiological saline was added to the infusate . Strict criteria for the management of the indwelling CVC were observed . The catheter tips were cultured after removal : only one was infected in the heparin group compared with nine in the control group . This significant reduction may have been due to the heparin preventing a fibrin sleeve from forming around the catheter tip . It is recommended that , as well as observing the usual aseptic pre caution s in managing the cannula , 500 units of heparin are added to each 500 ml of fluid infused to reduce the incidence of catheter-associated sepsis BACKGROUND Hemodialysis catheter thrombosis is associated with loss of catheter patency , catheter-related bacteremia and sepsis . To limit these risks , many renal units use heparin as a catheter-locking solution . In this study we investigate the effect of different concentrations of heparin catheter lock solution on systemic anticoagulation in an investigator-blinded r and omized study of patients with non-tunneled ( temporary ) central venous catheters . METHODS 28 consecutive patients requiring insertion of a temporary non-tunneled dual lumen central venous hemodialysis catheter were r and omly allocated to receive either heparin 5,000 IU/ml or heparin 1,000 IU/ml as catheter lock solutions . The primary outcome measure was the difference in activated partial thromboplastin time ( APTT ) at 10 minutes following catheter locking with heparin 5,000 IU/ml and heparin 1,000 IU/ml . Secondary outcomes included intradialytic blood flow rates , catheter removal due to insufficient hemodialysis blood flow to maintain hemodialysis and catheter-related bacteremia . RESULTS 13 patients were r and omized to the heparin 1,000 IU/ml group with 15 patients r and omized to the heparin 5,000 IU/ml group . There was a statistically significant increase in APTT at 10 minutes between groups with median + 22.2 % ( range 0 - 210 ) rise in APTT in the heparin 1,000 IU/ml group compared with + 373.7 % ( range 133 - 800 ) in the heparin 5,000 IU/ml group ( p < 0.001 ) . There was no statistically significant difference between groups with the secondary outcomes of intradialytic blood flow , catheter failure rates and catheter-related bacteremia rates . CONCLUSIONS Heparin 1,000 IU/ml catheter lock solution confers a significantly lower risk of systemic heparinization than heparin 5,000 IU/ml without any overtly detrimental effect on intradialytic blood flow , catheter failure rates and catheter-related bacteremia rates A prospect i ve analysis was conducted comparing dysfunction attributable to catheter thrombosis in subjects who received a heparin catheter lock three times a week ( n = 15 ) to those who received a heparin lock six times a week ( n = 15 ) immediately after the insertion of a temporary haemodialysis catheter . Thrombus related catheter removal occurred in two patients in control but no patients in the experiment group . Heparin locking six times a week was found to be effective in prolonging the mean of the first day where difficulty was experienced in aspiration . It also prevented any possible difficulty in catheter flushing . Increased locking frequency prevents any thrombus accumulation within the temporary catheter , while it has limited but significant preventive effect on thrombus accumulated around the catheter PURPOSE Our aim was to determine the non-inferiority of normal saline flushing compared to heparin flushing in maintaining the patency of totally implanted venous access devices ( TIVADs ) . METHOD Four hundred and thirty patients were recruited from 14 Italian centres . Patients were r and omized to heparin group or to normal saline group . The primary outcome of the study was TIVAD occlusion . RESULTS After r and omisation , 203 patients were assigned to normal saline group and 212 to heparin group . Median follow up time was 204 days in normal saline group and 294 in the heparin group . We observed 24 withdrawal occlusions ( 5.78 % ) : 10 in the heparin group and 14 in the normal saline group . One total occlusion was observed in the normal saline group . Taking as reference the arm treated with heparin , the absolute risk difference was 2.67 with the 90 % CI including the non - inferiority margin of 4 % . No significant difference between hazards of occlusion was found . CONCLUSIONS This study failed to demonstrate that normal saline flushing is not inferior to heparin flushing , even if a significant difference between the two treatments was not found . The use of heparin is controversial and other prospect i ve trials are necessary in this field . TRIAL REGISTRATION EudraCT number : 2009 - 013620 - 22 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 Intravascular abnormalities were well documented with central venous catheters . A prospect i ve r and omized study was undertaken to assess the actual incidence of such abnormalities with a silicone catheter and the effect of heparin in small doses on the formation of such abnormalities . Silicone catheters placed via the subclavian route were inserted for intravenous nutritional support . A st and ard solution of 5 % amino acid and 20 to 25 % dextrose was utilized and patients were r and omized to receive 1000 units of heparin per liter or no heparin . Catheter venograms were performed at the conclusion of therapy . Thirty-four patients were completed with 17 patients in the heparin group and 17 in the control group . There was obvious fibrin sleeve formation in nine of 17 ( 53 % ) in the heparin group and 11 of 17 ( 65 % ) in the control group . The duration of catheter stay correlates with the incidence of intravascular fibrin sleeve formation . Intravascular reactions to central catheters occur , regardless of catheter compositions , and result in fibrinous material adherent to the venous wall . Low doses of heparin do not eradicate this problem . Although fibrin sleeve formation was a significant problem , there was no incidence of central venous thrombosis when silicone catheters were utilized Background : Heparin has long been used to prevent thrombosis in the permanent central venous hemodialysis catheters ( PermCath ) . Other alternatives for heparin with fewer side-effects have recently been considered . We compared normal saline ( 0.9 % ) with heparin for flushing PermCath with regards to catheter patency and prevention of heparin complications . Material s and Methods : Chronic kidney disease patients who were c and i date of PermCath placement were r and omly assigned into two groups of heparin and saline . In the heparin group , the PermCath was flushed with heparin ( 1000 IU ) , and in the saline group , it was flushed with saline 0.9 % . Patients were followed for 24 hours , and outcomes included catheter thrombosis , maneuver needed to maintain catheter patency , and bleeding from catheter site . Results : Ninety six patients were included ( age = 63.1 ± 11.2 years , 54.2 % male ) . No one experienced catheter thrombosis . Two patient ( 4.2 % ) in the heparin and three ones ( 6.1 % ) in the saline group required catheter manipulation ( P = 0.520 ) . Four patients ( 8.5 % ) in the heparin and three ones ( 6.1 % ) in the saline group experienced bleeding ( P = 0.476 ) ; differences between heparin and saline groups in the amount of bleeding ( 225.0 ± 62.4 vs. 200.0 ± 113.5 cc , P = 0.721 ) and bleeding time ( 6.5 ± 1.2 vs. 5.3 ± 1.5 min , P = 0.322 ) were not significant . In the heparin group , no significant increase was observed in PTT over time ; baseline 30.9 ± 3.4 , 12 h 31.8 ± 3.4 , 24 h 31.2 ± 6.6 ( P = 0.628 ) . Conclusions : Flushing PermCath with normal saline 0.9 % is as effective as heparin in maintaining patency of the catheter , while it may reduce the risks associated with heparin Objective To assess the effect on circuit life in continuous venovenous haemodiafiltration ( CVVHD ) by manipulating heparin dilution and point of administration . Design Repeated crossover design . Cases were r and omised for first circuit and heparin dilution , after which crossovers occurred until treatment was stopped . Setting A 24-bed combined general and surgical intensive care unit admitting 1900 patients a year . On average , 54 cases a year receive CVVHD . Patients 26 critically ill adult patients requiring CVVHD were enrolled , 18 of whom used at least one st and ard circuit and one modified circuit . Interventions Two circuit configurations and heparin dilutions were compared . In combination A , st and ard CVVHD blood lines and heparin concentration ( 100 units/ml ) were used . In combination B , heparin was delivered in a more dilute volume ( 10 units/ml ) via a modified circuit design with an administration port immediately adjacent to the venous access . Measurements and results 18 r and omised crossovers of circuits A and B occurred . Mean/median circuit life for the st and ard heparin/circuit combination A was 20.1/17.5 ( SD 14.6 ) and for the modified combination B 21.4/15.4 ( SD 19.2 ) . There was no significant difference between circuits ( pairedt-test , p=0.8175 ) . To identify other factors which could have influenced circuit life ( platelet count , heparin dose and pre- and post-filter activated partial thromboplastin time , APTT ) all circuits terminated for the reasons identified ( n=105 ) were analysed using linear modelling . Survival analysis was used to determine the survival function of the circuit . Pre-heparin APTT was the only factor associated with an increase in filter life ( p=0.0325 ) . The hazard rate for filter failure was 0.049/h ( 95 % confidence interval 0.04 to 0.06 ) , the range of time until filters failed was 1.8 to 78.5 h. Conclusions Proximally administered dilute heparin is not associated with a significant increase in circuit life 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 Introduction / Significance / Population : Research has failed to demonstrate an optimal flushing solution or frequency for central catheters . In a 2002 study of 50 000 home care patients , catheter dysfunction with loss of patency was the most common complication and occurred in 29 % of the peripherally inserted central catheters ( PICCs ) tracked . With the advent of the Affordable Care Act and the promise of exp and ed home care services , this study offers evidence as to a preferred flushing protocol to prevent catheter patency complications for home infusion patients with PICCs . Methods : This prospect i ve , r and omized , 1-way , single-blinded posttest with control group study was performed to compare 3 commonly used flushing protocol s in home infusion patients with PICCs . The independent variable was the flushing protocol , and dependent variables included the development of patency-related complications and other significant issues such as sluggishness , occlusion , missed medication doses , catheter replacement , additional nursing visits , and the use of alteplase ( Cathflo Activase ) . Data Analysis / Results : Each of the study groups had patients who experienced 1 or more patency-related complications . Additional factors that may affect catheter function , including patient age , gender , diagnosis , therapy type , frequency of catheter use , catheter br and /size/number of lumens , concomitant use of anticoagulant medications , and whether PICCs were used for routine lab testing , were analyzed , and no statistical significance was determined . Catheter dwell time ( catheter days ) was statistically significant ( p = .003 , confidence interval = 95 % ; assuming equal variance ) and confirmed the assumption that the longer a home care patient 's catheter was in place , the more complications occurred . There were no cases of heparin allergy , heparin-induced thrombocytopenia , or line infection . Discussion / Conclusion / Recommendations for Practice : The data provide some evidence to support the elimination of heparin flushing in home care patients with PICCs , although data in the saline-only group that related to additional registered nurse visits to assess PICC patency and the use of alteplase ( Cathflo Activase ) were trending toward significance because this group experienced a higher incidence of these complications than both the heparin groups . These findings should not be translated to home care patients with cancer or pregnancy diagnoses because these population s were excluded from this study . More studies of this topic area should be initiated . Please see video abstract , Supplemental Digital Content 1 , for more information ( http://links.lww.com/JIN/A3 ) BACKGROUND AND OBJECTIVES Upper extremity thrombosis is a major complication of central venous catheters implanted for chemotherapy in cancer patients . Vitamin K antagonists and low-molecular-weight heparins have been recommended in this setting , but their relative benefit-to-risk ratios have never been compared . DESIGN AND METHODS A prospect i ve , r and omized , open , parallel-group , multicenter trial was performed comparing the antithrombotic efficacy and safety of warfarin and the low-molecular-weight heparin , nadroparin , in cancer patients who had undergone central venous catheter implantation . Warfarin was given orally at a fixed daily dose of 1 mg and nadroparin was injected subcutaneously at a fixed daily dose of 2,850 IU for 90 days , or until venographically-confirmed thrombosis occurred . The primary efficacy outcome was the occurrence of upper extremity thrombosis confirmed by venography performed 90 days after insertion of the catheter , or earlier if symptoms of thrombosis had appeared . Safety end-points were bleeding and thrombocytopenia . RESULTS Fifty-nine patients were included in the study . A total of 21 and 24 patients in the nadroparin and warfarin groups , respectively , were evaluable for primary efficacy . Six out of the 21 patients in the nadroparin group ( 28.6 % ) and 4 out of the 24 patients in the warfarin group ( 16.7 % ) had venographically-documented upper extremity thrombosis at day 90 ( p=0.48 ) . Safety was satisfactory and similar with both treatments . INTERPRETATION AND CONCLUSIONS Warfarin at a fixed , very low dose and nadroparin at a fixed , prophylactic dose had comparable benefit-to-risk ratios in the prevention of thrombosis associated with central venous catheters in cancer patients OBJECTIVE : To compare the use of in-line filtration with the addition of heparin/hydrocortisone ( hep/hc ) to the infusate for both phlebitis prevention and intravenous(iv ) line survival in peripheral iv catheters . This study was specific for a patient group receiving prolonged courses of iv antibiotics . Analysis of the two endpoints for conventional short iv catheters ( short lines ) versus long ( 30 cm ) iv catheters ( long lines ) was also performed . METHODS : Patients with cystic fibrosis receiving intermittent iv antibiotics were r and omly allocated to receive their drugs either through an in-line filter using a drug-free infusate or with no filter and an infusate containing heparin 500 units and hydrocortisone 10 mg/L. Infusion sites were assessed daily . RESULTS : Both the hep/hc and filter groups were similar in terms of phlebitis incidence and iv line survival when analyzed separately for both short and long lines . Long lines displayed markedly prolonged survival times and reduced phlebitis compared with short lines . CONCLUSIONS : The effectiveness of iv filters in excluding the large particle load introduced by iv antibiotics and hence in reducing the subsequent phlebitis makes them a useful alternative to the use of hep/hc . The use of filters in this patient group may offer advantages in terms of ease of use and a possible decrease in hep/hc-related problems . Long lines offer practical advantages over short lines for patients requiring longer term iv access In order to evaluate a new method of heparinization , uncoated ( 22 ) and heparin‐coated ( 27 ) central venous polyethylene catheters were inserted in 49 patients via basilic and cephalic veins punctured at the fossa cubiti . The mean duration of catheterization was 5.7 ( 1–11 ) days . One‐third of the patients with heparin‐coated catheters , and one sixth with uncoated catheters developed clinical thrombophlebitis , with a maximum incidence between 4 and 8 days after catheterization . A higher risk of developing thrombophlebitia in the first 4 days after catheterization was found in the patients with heparin‐coated polyethylene catheters . After 8 days of catheterization , it seems that there is a lower risk of new cases of thrombophlebitis appearing both in patients with uncoated and those with heparin‐coated polyethylene catheters . Radiological thrombosis , regardless of duration of catheterization and heparin‐coating , was demonstrated in all 22 patients investigated by “ pull‐out ” phlebography . The heparin‐coating did not decrease the rate of thrombotic complications . Location of the catheter tip in subclavian veins was associated with a significantly higher incidence of large , parietal thrombi and catheter occlusion than when the tip was situated in anonymous veins , the superior vena cava , or the right atrium . Cannulation by heparin‐coated , polyethylene tubing did not reduce the rate of catheter occlusion BACKGROUND Tunneled-cuffed catheters ( TCC ) are often used among the elderly to commence and carry out haemodialysis ( HD ) . Complications like infection and thrombosis frequently reduce the lifespan of TCC . The role of an antibiotic heparin ' lock ' in the prevention of thrombotic and infectious complications and enhancement of TCC survival in the elderly has not been investigated previously . METHODS In this prospect i ve , double-blind clinical trial , TCC ( n = 119 , placed among 113 elderly patients requiring HD during March 2002 - February 2003 ) were r and omised to either group I having TCC ( n = 59 , placed in 58 elderly patients ) locked with cefotaxime ( 10 mg/mL ) and heparin ( 5000 U/mL ) , or group II with TCC ( n = 60 , placed in 55 elderly patients ) having catheter-restricted filling of heparin ( 5000 U/mL ) alone . Symptomatic catheter-related blood stream infections ( CRBSI ) and catheter thrombosis were the primary end points in this study . Thrombosis was defined as an inability to use the catheter at a blood flow of 200 mL/min that did not respond to catheter repositioning and /or intraluminal thrombolysis . The incidence of catheter thrombosis , CRBSI and percentage of catheter survival were estimated and statistically compared between the two groups . RESULTS Kaplan-Meier survival analysis using log rank test showed higher thrombosis-free TCC survival ( 84.7%vs 63.3 % , P = 0.021 ) , infection-free survival ( 68.7%vs 31.3 % , P < 0.001 ) and infection and thrombosis-free survival ( 65.0%vs 35.0 % , P = 0.006 ) at 365 days in group I compared with group II . CONCLUSION Cefotaxime and heparin locks safely and effectively enhance the lifespan of TCC by lowering the incidence of thrombotic and infectious complications among elderly end-stage renal failure ( ESRD ) patients Heparin and saline are commonly used to fill hemodialysis central venous catheters to prevent their thrombosis during the interdialytic period . The purpose of this prospect i ve clinical study was to evaluate whether replacing heparin with citrate or polygeline could ensure satisfactory catheter function without exposing patients to the risk of systemic heparinization . Thirty end-stage renal disease ( ESRD ) patients with subclavian or jugular single lumen catheters as temporary vascular access for hemodialysis were enrolled . After the insertion of the catheters , the patients were r and omly assigned to one of the following three filling groups : Group A , heparin ; Group B , citrate ; Group C , polygeline . Before each dialysis , the filling solution was aspirated and clot volume , if present , was measured . The catheter usage time and the clot volume were 23 + /- 24 days and 0.052 + /- 0.035 ml in Group A , 51 + /- 36 days and 0.059 + /- 0.032 ml in Group B , and 32 + /- 10 days and 0.056 + /- 0.038 ml in Group C , respectively . Our results indicate that citrate or polygeline can replace heparin effectively as a filling solution for single lumen temporary hemodialysis catheters We evaluated the efficacy of a vancomycin solution in the prevention of bacteremia caused by vancomycin-sensitive organisms ( VSO ) in cancer patients with a tunneled central venous catheter ( CVC ) . Eighty-three patients who had a single lumen CVC were r and omized to use a heparin solution ( 25 U/ml ) for daily catheter flush with ( HepVan ) or without ( Hep ) vancomycin , 25 mcg/ml . Febrile episodes were recorded , and central and peripheral blood cultures were drawn before beginning antibiotic therapy . Patients participated in follow-up to 16,677 catheter days ( 8,666 Hep and 8,011 HepVan ) , and 143 febrile episodes were recorded ( 82 Hep and 61 HepVan ) . Forty-four episodes of bacteremia occurred , 23 of them due to VSO ( 16 occurred in the Hep group and 7 in the HepVan group ( P = 0.19 ) . VSO bacteremia occurred in 14 neutropenic ( absolute neutrophil count < 500 x 10(9)/l ) episodes ( 7 Hep vs. 7 HepVan ) and in 9 non-neutropenic episodes ( 9 Hep vs. O HepVan ; P = 0.013 ) . Vancomycin effectively prevented bacteremia by VSO in non-neutropenic patients , supporting the idea that intraluminal colonization of indwelling CVCs contributes to bacteremia only in these patients We have conducted a prospect i ve r and omized controlled trial to evaluate the role of low-dose unfractionated heparin prophylaxis in preventing central venous line-related thrombosis in patients with haemato-oncological disease . Patients were r and omly assigned to receive either prophylactic intravenous unfractionated heparin ( continuous infusion of 100 IU/kg/daily ) or 50 ml/daily of normal saline solution as a continuous infusion . CVLs were externalized , non tunneled , double lumen catheters . All CVLs were placed percutaneously by the same physician in the subclavian vein . Upper limb veins were systematic ally examined by ultrasonography just before , or < 24 hours after , catheter removal , and in case of clinical signs of thrombosis . One hundred and twenty-eight CVLs were inserted . Catheter-related thrombosis occurred in 1.5 % of the catheters inserted in patients of the heparin group , and in 12.6 % in the control group ( p = 0.03 ) . No other risk factors were found for the development of catheter-related thrombosis . Two and three patients experienced severe bleeding in the heparin group , and in the control group , respectively ( p = 0.18 ) . There were no other side-effects clearly ascribable to the use of unfractionated heparin . This is the first prospect i ve , r and omized study , which shows that low-dose of unfractionated heparin is safe and effective to prevent catheter-related thrombosis in patients with haemato-oncological disease Catheter‐related venous thrombosis is one of the most frequent complications of central venous catheters ( CVCs ) . This complication occurs in 4– 40 % of patients with hematologic malignancies receiving conventional chemotherapy after placement of CVCs Background . Infants with congenital heart disease who require central venous lines are at increased risk of thrombosis . Heparin-bonded catheters provide protection from thrombotic events in some children . However , heparin-bonded catheters may not be as effective in infants ≤1 year old because of other potential risk factors ( smaller vessel size , longer duration of catheter use ) . No studies have assessed the benefit of heparin-bonded catheters in such specific high-risk population s. The objective of this study was to assess the efficacy of heparin-bonded catheters for preventing thrombosis in infants aged ≤1 year with congenital heart disease . Study Design . This study was design ed as a r and omized , controlled , blinded single-center trial . Infants ≤1 year old with congenital heart disease requiring a central venous line for clinical care were r and omly assigned to receive either a heparin-bonded catheter or a st and ard non – heparin-bonded catheter . Catheters were visually indistinguishable . The primary outcome was incidences of both silent and clinical ly noticeable thrombosis confirmed by ultrasound . Ultrasounds were review ed by a blinded central adjudication committee . Interim analysis was performed after enrollment of 97 patients . Results . Eighty-seven patients were evaluable ( 41 of the patients were female ) . Thrombotic events occurred in 17 ( 42.5 % ) of 40 patients in the non – heparin-bonded catheter group and in 21 ( 44.7 % ) of 47 patients in the heparin-bonded catheters group . The study was stopped when the interim analysis showed convincing evidence for no difference between groups over the alternative hypothesis of 50 % risk reduction . Conclusions . Infants with congenital heart disease are at significant risk of both silent and clinical ly identified thrombosis . There seems to be no advantage in using heparin-bonded catheters in infants ≤1 year of age A r and omized controlled study was done to determine whether the addition of heparin , in very low concentration ( 0.25 U/ml ) , to fluids administered through an umbilical artery catheter ( UAC ) would affect the duration of catheter patency . UAC occlusion occurred in 2 of 15 patients in the heparin group and in 11 of 15 patients in the control group ( p = 0.001 ) . Using life-table analysis , the functional life span of UAC was estimated . On day 8 , 100 % of UACs in heparin group and 9 % of UACs in control group were patent ( p < 0.05 ) . Coagulation profile remained unaltered after addition of heparin compared with that before the start of the therapy . There was no difference in the incidence of subependymal intraventricular hemorrhage between the two groups . It is concluded that heparin in such low concentration is effective in prolonging duration of UAC patency without causing adverse effects There is growing concern about the development of antibacterial resistance with the use of antibiotics in catheter lock solutions . The use of an antibiotic that is not usually used to treat other serious infections may be an alternative that may reduce the clinical impact should resistance develop . We conducted a r and omized controlled trial to compare a solution of minocycline and EDTA with the conventional unfractionated heparin for the prevention of catheter-related bacteremia in hemodialysis patients during a period of 90 d. The study included 204 incident catheters ( 27.8 % tunneled ) ; 14 catheters were excluded because of early dysfunction and 3 because of protocol violations . We observed catheter-related bacteremia in 19 patients in the heparin group ( 4.3 per 1000 catheter-days ) and in 5 patients in the minocycline-EDTA group ( 1.1 per 1000 catheter-days ; P = 0.005 ) . We did not detect a significant difference in the rate of catheter removal for dysfunction . Catheter-related bacteremia-free survival was significantly higher in the minocycline-EDTA group than in the heparin group ( P = 0.005 ) . In conclusion , a minocycline-EDTA catheter lock solution is effective in the prevention of catheter-related bacteremia in hemodialysis patients BACKGROUND AND OBJECTIVE We previously demonstrated that minocycline-EDTA was efficacious at preventing catheter-related bloodstream infections ( BSIs ) in three patients with recurrent infections . This study compared heparin with minocycline-EDTA as flush solutions used among dialysis patients with central venous catheters , a high-risk group for catheter-related BSI . METHODS Patients were enrolled within 72 hours of catheter insertion and r and omized to receive heparin or minocycline-EDTA as a flush after each dialysis session . Each syringe containing flush solution was wrapped in orange plastic to conceal the type of solution it contained . Patients were observed for evidence of infection and catheter thrombosis . After catheters were removed , cultures were performed to determine whether microbial colonization had occurred . RESULTS During a 14-month period , 60 patients were enrolled ( 30 in each group ) . The two groups had similar demographics and underlying diseases . Catheter survival at 90 days was 83 % for the minocycline-EDTA group versus 66 % for the heparin group ( P = .07 ) . Significant catheter colonization , a surrogate measure of catheter-related infection , was significantly more frequent in the heparin group ( 9 of 14 vs 1 of 11 ; P = .005 ) . There was only one catheter-related bacteremia and it occurred in the heparin group . CONCLUSIONS When compared with heparin , minocycline-EDTA had a better 90-day catheter survival ( P = .07 ) and a decreased rate of catheter colonization . This pilot study warrants a larger prospect i ve , r and omized trial Abstract Background : Tunneled venous access devices ( VADs ) are often essential in the care of patients with advanced malignancies , but they carry an uncertain risk of thrombosis . Methods : To determine the incidence of venoocclusion related to silicone VADs in a population of adult oncology patients , we prospect ively studied 50 individuals with upper extremity venograms ∼6 weeks after their VADs had been implanted . Twenty-one of these patients were reevaluated with venograms ∼12 weeks after catheterization . In addition , venograms were performed on a separate group of 24 patients who needed catheterization of axillary-subclavian veins that had been catheterized in the past . Results : The 6-week venograms in the prospect i ve study showed partial venous obstruction in 15 patients ( 30 % ) , whereas three ( 6 % ) had developed symptomatic total venoocclusion by this time . The 12-week venograms showed two additional complete occlusions . Venograms of 30 previously catheterized veins showed complete venoocclusion in nine ( 30 % ) , although only two had a history of thrombosis . Conclusions : Our observations indicate that VADs frequently cause partial venoocclusion within the first 6 weeks of catheterization and that permanent venous damage from VADs is common , even without a history of VAD-related thrombosis Background Chronic oral anticoagulation is currently used to avoid thrombosis and the malfunction of tunneled cuffed catheters ( TCCs ) for hemodialysis ( HD ) . The aim of the study was to assess the efficacy of early warfarin administration , after TCC placement , in comparison to its administration after the first thrombosis or malfunction event of the TCC . Patients and methods One hundred and forty-four chronic dialysis patients , who underwent TCC placement between June 2001 and June 2005 , were r and omized into two groups : 81 patients , group A , started oral anticoagulation 12 hr after the TCC placement ( target international normalized ratio ( INR ) 1.8–2.5 ) , in association with ticlopidine 250 mg/die ; 63 patients , group B , started warfarin after the first thrombosis/malfunction episode ( target INR 1.8–2.5 ) in association with ticlopidine 250 mg/die . The efficacy of oral anticoagulation therapy in preventing TCC thrombotic complications was evaluated in a 12-month follow-up period , after TCC placement , in terms of : a ) the number of patients with thrombotic-malfunction events ; b ) the number of thrombotic-malfunction events with urokinase infusion ( events/patient/year ) ; c ) intradialytic blood flow rate ( BFR , ml/min ) ; d ) negative blood pressure ( BP ) from the arterial line of the TCC ( AP , mmHg ) ; e ) positive BP , in the extracorporeal circuit from the venous line ( VP , mmHg ) ; and f ) bleeding complications . Results Ten patients ( 12 % ) in group A showed TCC thrombosis/malfunction vs. 33 patients ( 52 % ) in group B ( p<0.01 ) . In group A , 0.16 events of thrombosis/malfunction per patient/year vs. 1.65 in group B ( p<0.001 ) were observed . BFR was respectively 305 ± 34 vs. 246 ± 42 ml/min ( p<0.001 ) . AP was –124 ± 13 in group A vs. –174 ± 21 mmHg in group B ( p<0.05 ) . VP was 112 ± 28 in group A vs. 168 ± 41 mmHg in group B ( p<0.05 ) . No patient showed any bleeding events . Conclusions Early warfarin therapy allows a significant reduction in TCC thrombotic complications and an improvement in both arterial and venous fluxes in comparison with the same therapy administered after the first TCC thrombotic/malfunction event . This therapy did not induce any bleeding complications in the patients included in the study Total intraparenteral nutrition therapy using an endocaval catheter is subject to complications due to the catheter itself and to the onset of phlebothrombosis of the venous district involved . Two groups of patients suffering from abdominal surgical pathologies requiring prolonged postoperative parenteral treatment were subjected to antithrombotic prophylaxis . In the first group of 20 patients , calciheparin u.s . was used and in the second defibrotide in the doses recommended in the literature . Serial lab screening of certain clotting parameters was carried of the brachio-subclavio-caval district . In the calciheparin group , the trend of certain examinations shows , as usual , a change in parameters in agreement with the drug 's anticlotting action ; in the group treated with defibrotide , the haemostatic balance is respected : the angiographies never showed intimal lesion or phlebothrombosis in either group . The usefulness of correct antithrombotic prophylaxis in these patients is confirmed and it is pointed out that defibrotide is more flexible and h and y and that it can be used in patients in whom calciheparin is potentially risk 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 A total of 23 patients who developed heparin-induced thrombocytopenia following exposure to heparin solely due to intravascular catheter or filter flush were the subjects of prospect i ve studies of argatroban therapy . Heparin doses were 10 - 13,000 U , with a mean exposure of 8+/-4 days . Following heparin-induced thrombocytopenia diagnosis and heparin cessation , 13 patients received argatroban ( mean dose of 1.8+/-1.1 mg/kg/min for 5.5+/-3.9 days ) , achieving activated partial thromboplastin times of 63+/-23 seconds , and 10 historical control patients received no direct thrombin inhibitors . Platelet count recovered to a mean of 207+/-153 x 10(9)/L ( n=12 ) after 5.5+/-3.9 days of argatroban therapy and to a mean of 127+/-63 x 10(9)/L ( n=8 ) 5 days after baseline in the control group . A composite end point of death , amputation , or new thrombosis within 37 days occurred in five ( 38.5 % ) argatroban-treated patients and four ( 40 % ) controls . Death was the most common untoward outcome ( approximately 30 % of each group ) . No argatroban-treated patient and two ( 20 % ) control patients experienced new thrombosis . Major bleeding was comparable between groups . Heparin-induced thrombocytopenia can occur following minimal heparin exposure , including heparin flushes ; in these patients , argatroban provides effective alternative anticoagulation as compared with historical controls BACKGROUND Three meta-analyses conducted in the 1990s concluded that the effect of intermittent flushing with heparin at low concentration ( 10 U/mL ) was equivalent to that of 0.9 % sodium chloride flushes in preventing occlusion or superficial phlebitis . No firm conclusion was reached on the safety and efficacy of heparin concentrations of 100 U/mL used as an intermittent flush . PURPOSE To determine whether flushing peripheral intravenous catheters with 3 mL of a 100 U heparin/mL solution instead of saline improves the outcome of infusion devices . METHODS Cluster-r and omized , controlled , two-arm , open trial , conducted in a research and teaching hospital in Northern Italy , involving 214 medical patients without contraindications to heparin : 107 r and omly allocated to heparin and 107 to saline flushes ( control group ) . Main outcome measure was catheter occlusion and catheter-related phlebitis . RESULTS Patients with either phlebitis or occlusion were 45 ( 42.1 % ) in the heparin group and 68 ( 63.6 % ) in the saline group ( OR 0.41 ; 95 % CI 0.24 - 0.72 ; p= 0.002 ) ; patients with occlusion alone were 23 ( 21.5 % ) and 47 ( 43.9 % ) , respectively ( p= 0.03 ) ; patients with phlebitis alone were 28 ( 26.2 % ) and 56 ( 52.6 % ) respectively ( p= < 0.001 ) . Similar results were obtained when the analysis was based on catheters . No heparin severe side effects were identified . LIMITATIONS Lack of blinding , patient selection , cluster r and omization of periods of treatment . CONCLUSIONS Heparin 100 U/mL in the maintenance of peripheral venous catheters was more effective than saline solution , in that it reduced the number of catheter-related phlebitis/occlusions and the number of catheters per patient , with potential advantages to both patients and the health system . It also appeared safe . However , subjects with platelet or coagulation defects were excluded , and , therefore , caution should be used when prescribing this type of catheter maintenance to patients at risk of bleeding In a double-blind study , heparin sodium was compared with 0.9 % sodium chloride injection for use in maintaining patency of indwelling devices for intermittent intravenous infusion . Adult patients who required intermittent intravenous devices were r and omly assigned to receive 1 mL of a heparin sodium 100 units/mL flush solution or a 0.9 % sodium chloride flush solution . Observations were recorded for each catheter , rather than for each patient . Patients were evaluated daily for the development of phlebitis . In the 160 patients for whom complete data on catheter patency were available , there were 307 observations ( 170 for the heparin group and 137 for the sodium chloride group ) . No significant difference in the duration of catheter patency or incidence of phlebitis was observed between the groups . A difference in the incidence of phlebitis could not be excluded with confidence , but inasmuch as there was no effect on duration of catheter patency , the clinical importance of this superficial venous phlebitis is question able . The duration of patency was significantly greater in men than in women . The use of penicillins , cephalosporins , or clindamycin , alone or in combination , was significantly associated with the development of phlebitis for both treatment groups . No other factors were found to correlate with either the duration of catheter patency or incidence of phlebitis . The results of this study indicate that heparin offers no advantage over 0.9 % sodium chloride injection in maintaining the patency of intermittent intravenous devices INTRODUCTION Arterial catheters are widely used in intensive care units for continuous blood pressure monitoring and blood sampling . Studies have examined the effect of heparin on patency of arterial catheters but not on platelet counts . Heparin is a naturally occurring anticoagulant that helps prevent clotting and is given to prevent and treat thrombosis . It has many other effects , including reducing platelet counts . METHODS A prospect i ve , r and omised , double-blind study compared the effects of heparinised and normal saline ( both administered via a continuous flush device to an arterial catheter ) on patients ' platelet counts . All patients admitted to a mixed medical-surgical ICU between April and December 2003 were eligible for entry . Exclusion criteria were age under 16 years , known sensitivity to heparin , pre-existing coagulopathy that precluded heparin , or requirement for therapeutic heparin . Lines were inserted into radial , brachial or femoral arteries . A 500 mL bag of saline for the flush was injected with numbered syringes , containing either normal saline ( NS , 35 patients ) or 500 IU heparin ( HS , 30 patients ) , and pressurised . Platelet count was assessed daily . RESULTS Mean platelet counts were 234.6 x 10(9)/L ( NS ) versus 256.6 x 10(9)/L ( HS ) . Comparison using the central limit theorem showed means were not different at the 95 % confidence interval ( - 77.6 to 37 x 10(9)/L ) . CONCLUSION Use of heparin in normal saline as a continuous flush for an arterial catheter does not reduce platelet counts in critically ill patients Objective To compare the incidence of catheter colonization and catheter-related bloodstream infections between heparin-coated catheters and those coated with a synergistic combination of chlorhexidine and silver sulfadiazine . Design R and omized , controlled clinical trial . Setting A 20-bed medical-surgical intensive care unit . Patients A total of 180 patients requiring the insertion of a trilumen central venous catheter . Interventions Patients were r and omized to receive either a trilumen heparin or chlorhexidine and silver sulfadiazine-coated catheter . Measurements Catheter colonization was defined by a semiquantitative catheter tip culture yielding 15 or more colony-forming units or quantitative culture of 1,000 or more colony-forming units/ml . Catheter-related bloodstream infection as the isolation of the same microorganism from a peripheral blood culture and catheter tip . Results A total of 260 catheters were cultured . Out of 132 heparin-coated catheters , 29 were colonized and out of 128 chlorhexidine and silver sulfadiazine- coated catheters , 13 were colonized ( p=0.03 ) , relative risk RR=2.16 ( 1.18–3.97 ) . This represents an incidence of 23.5 and 11.5 episodes of catheter colonization per 1,000 catheter-days , respectively ( p=0.0059 ) , RR=2.04 ( 1.05–3.84 ) . Microorganisms isolated in catheter colonization from heparin-coated catheters were gram-positive cocci 23 , gram-negative bacilli 7 , and C and ida spp 4 . In chlorhexidine and silver sulfadiazine-coated catheters were gram-positive cocci 6 and gram-negative bacilli 11 ( p=0.009 ) . The incidence of catheter-related bloodstream infections per 1,000 catheter-days was 3.24 in heparin-coated catheters and 2.6 in chlorhexidine and silver sulfadiazine-coated catheters ( p=0.79 ) , RR=1.22 ( 0.27–5.43 ) . Conclusions In critically ill patients the use of trilumen central venous catheters coated with chlorhexidine and silver sulfadiazine reduced the risk of catheter colonization due to prevention of gram-positive cocci and C and ida spp Although it is recognized that the addition of heparin to total parenteral nutrition solutions reduces subclavian vein thrombosis from percutaneous polyethylene catheters , it does not affect the low thrombosis rate associated with polyurethane catheters . It has been suggested that heparin also reduces catheter sepsis during total parenteral nutrition . We review ed the sepsis rate in 86 patients r and omized to receive iv nutrition with or without heparin through polyethylene , polyvinyl , and polyurethane catheters . Blood was drawn from febrile patients for culture ; if positive , catheters were removed and the tips cultured . Catheters were considered infected if blood and catheter tips were positive , or if fever disappeared within 48 hr after catheter removal , even if cultures were negative . Catheter sepsis occurred in two patients in both groups . It appears that heparin does not reduce sepsis from percutaneous subclavian vein catheters . Although its use may be indicated to reduce thrombosis associated with polyethylene catheters , there is no indication for its use to reduce sepsis with either type of catheter OBJECTIVE To determine whether very low doses of warfarin are useful in thrombosis prophylaxis in patients with central venous catheters . DESIGN Patients at risk for thrombosis associated with chronic indwelling central venous catheters were prospect ively and r and omly assigned to receive or not to receive 1 mg of warfarin , beginning 3 days before catheter insertion and continuing for 90 days . Subclavian , innominate , and superior vena cava venograms were done at onset of thrombosis symptoms or after 90 days in the study . RESULTS One hundred twenty-one patients entered the study , and 82 patients completed the study . Of 42 patients completing the study while receiving warfarin , 4 had venogram-proven thrombosis . All 4 had symptoms from thrombosis . Of 40 patients completing the study while not receiving warfarin , 15 had venogram-proven thrombosis , and 10 had symptoms from thrombosis ( P less than 0.001 ) . There were no measurable changes in the coagulation values assayed due to this warfarin dose , except in occasional patients who had become anorectic because of their disease or chemotherapy . CONCLUSIONS Very low doses of warfarin can protect against thrombosis without inducing a hemorrhagic state . This approach may be applicable to other groups of patients 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 OBJECTIVE To compare the efficacy of two available preparations ( heparin , 10 U/mL , 1 mL , vs. normal saline , 1 mL ) used for maintaining patency in peripheral intravenous ( IV ) locks during pregnancy . DESIGN Prospect i ve , r and omized , and double-blind . Eligible patients who were to receive a peripheral intermittent IV lock were r and omly assigned to receive either heparin flushes or normal saline flushes for IV lock maintenance . IV locks were flushed after each medication administration , or at least every 24 hours , with the assigned blinded flush solution . Intermittent IV lock sites were also evaluated every 12 hours for the development of phlebitis . SETTING A large academic medical center in the Midwest that has both community-based and regional-referral obstetric practice s with more than 2,000 deliveries per year . PARTICIPANTS A convenience sample included 73 hospitalized pregnant women who were between 24 and 42 weeks gestation . Exclusions from the study were women with significant abnormalities in the fetal heart tracing on admission , cervical dilation > 4 cm , presence of hypersensitivity to heparin , presence of clotting abnormalities , and anticoagulation therapy ( including low-dose aspirin ) . RESULTS Data indicate there were no statistically significant differences in IV lock patency nor in phlebitis between heparin or normal saline flushes . CONCLUSIONS This study provides support that both normal saline and heparin in the doses studied may be equally effective in the maintenance of peripheral IV locks . Due to small sample size , additional studies are needed to determine optimal therapy over time PURPOSE To determine the safety and efficacy of weekly prophylactic urokinase therapy in tunneled central venous access devices ( VADs ) . MATERIAL S AND METHODS A prospect i ve , r and omized study was performed in 105 patients who underwent tunneled VAD placement between March 1997 and April 1998 . The patients were r and omized to receive either twice-daily heparin flushes ( 14 heparin flushes per week ; group A , n = 52 ) or twice-daily heparin flushes with once-weekly urokinase ( UK ) instillation ( 13 heparin flushes , one UK flush per week ; group B , n = 53 ) . Patients were followed up by examination and /or interview at 1 , 3 , and 6 months for signs and symptoms of delayed catheter-related complications . RESULTS The total number of indwelling catheter-days was similar between groups ( 5,450 in group A , 5,276 in group B ) . The total number of infectious complications and fibrin sheaths formed was greater for group A ( n = 11 ; 21.1 % ) than group B ( n = 3 ; 5.7 % ) ( P = .02 ) . There were no side effects noted from the prophylactic UK administrations . CONCLUSION Prophylactic UK is advantageous in preventing delayed catheter-related complications The use of antibiotic lock solutions ( ALSs ) for the prevention of catheter-related blood stream infections ( CRBSIs ) is a promising option . The efficacy and safety of linezolid as ALS were evaluated in a r and omized double-blind prospect i ve study where 131 patients who required nontunneled catheter ( NTC ) for hemodialysis ( HD ) were r and omized to receive an ALS with either ( A ) unfractionated heparin ( 2000 U/ml ) alone as a catheter lock control , ( B ) vancomycin ( 5 mg/ml ) + heparin ( 2000 U/ml ) , or ( C ) linezolid ( 2 mg/ml ) + heparin ( 2000 U/ml ) . The primary endpoint of the study was CRBSI . A total of 152 NTCs were inserted in 131 patients . The linezolid-locked group did not present any infective episode ( CRBSI rate = 0/1000 catheter days ) compared with 2 episodes in the vancomycin-locked group ( CRBSI rate = 1.21/1000 catheter days , p = 0.1021 ) and 11 episodes in the heparin-locked group ( CRBSI rate = 6.7/1000 catheter days , p = 0.0001 ) . Median number of catheter days was greater in group C ( median = 38 ) compared with group B ( median = 36 , p = 0.0415 ) and with group A ( median = 34 , p = 0.0036 ) . No side effects and no resistant organisms were recorded with the use of linezolid ALS . Linezolid appears to be a safe and effective ALS , preventing CRBSI and prolonging the survival of the catheter in HD patients Bloodstream infections related to the use of central venous catheters are an important cause of patient morbidity , mortality , and increased health care costs . Catheter-related infection may be due to fibrin deposition associated with catheters . Interventions design ed to decrease fibrin deposition have the potential to reduce catheter-related infections . This study was a r and omized , controlled trial in which 246 patients with nontunneled central venous catheters were r and omly assigned to receive a heparin-coated catheter with 50 mL/d of normal saline solution as a continuous infusion ( heparin-coated group ) or a noncoated catheter with a continuous infusion of low-dose unfractionated heparin ( control group : continuous infusion of 100 U/kg/d ) . Catheter-related bloodstream infection occurred in 2.5 % ( 3/120 catheters ) in the heparin-coated group ( 0.9 events per 1,000 days ) and in 9.1 % ( 11/120 catheters ) in the control group ( 3.5 events per 1,000 days ; P = 0.027 ) . No other risk factors were found for the development of catheter-related bloodstream infection . Six and seven patients experienced severe bleeding in the heparin-coated and control groups , respectively ( P = 1.00 ) . We did not observe heparin-induced thrombocytopenia . The use of heparin-coated catheters can be a safe and effective approach to the prevention of catheter-related bloodstream infection in patients with hematooncologic disease In a prospect i ve r and omised trial patients receiving multiple-day chemotherapy and heparin had significantly fewer local complications at the site of venous access than patients who had chemotherapy alone . The need to move peripheral venous catheters to other sites was decreased significantly , from 36 % to 6 % . Prophylaxis of phlebitis with low-dose continuous heparin is safe , simple , cheap and effective . It facilitates administration of multiple-day chemotherapy for the patients , the nurses and the physicians The purpose of this study was to compare the effectiveness of 1 ml of 0.9 % sodium chloride with 10 units of heparin in 1 ml sodium chloride solution , both containing benzyl alcohol , in maintaining patency and reducing the incidence of phlebitis in patients with intermittent infusion devices . The subjects ( N = 32 ) were r and omly assigned in a double-blind experimental design . Repeated- measures analysis of variance revealed no significant difference between the groups in phlebitis or patency variables . The results from this controlled study would suggest that 0.9 % sodium chloride is as effective as 10 units of heparin in sodium chloride solution in maintaining intermittent infusion device patency and preventing phlebitis PURPOSE The extent of venous thromboembolism ( VTE ) associated with central vein catheters ( CVC ) in cancer patients remains unclear . The aim of this study was to evaluate the efficacy and safety of the low molecular weight heparin , enoxaparin , in the prevention of VTE . PATIENTS AND METHODS In a multicenter , double-blind study , consecutive cancer patients scheduled for CVC insertion were r and omly assigned to receive either subcutaneous enoxaparin 40 mg once a day or placebo . Treatment was started 2 hours before CVC insertion and continued for 6 weeks . The primary end points of the study were deep vein thrombosis ( DVT ) , confirmed by venography of the CVC limb performed 6 weeks after r and omization , or clinical ly overt pulmonary embolism , confirmed by objective testing during the study drug administration . Patients were assessed for bleeding complications . RESULTS Three hundred eighty-five patients were r and omized , of which 321 ( 83.4 % ) underwent venography . A venography was adequate for adjudication in 155 patients in each treatment group . A DVT was observed in 22 patients ( 14.1 % ) treated with enoxaparin and in 28 patients ( 18.0 % ) treated with placebo , corresponding to a relative risk of 0.78 ( 95 % CI , 0.47 to 1.31 ) . No major bleeding occurred . Five patients ( 2.6 % ) in the enoxaparin group and two patients ( 1.0 % ) in the placebo group died during the treatment period . CONCLUSION In this study , no difference in the rate of CVC-related VTE was detected between patients receiving enoxaparin and patients receiving placebo . The dose of enoxaparin used in this study proved to be safe . Clinical trials evaluating higher enoxaparin doses could optimize the efficacy of this agent for this indication Hickman catheters ( HC ) are associated with complications , in particular infection , occlusion and thrombosis . We tested the hypothesis that regular flushing of catheters with urokinase would reduce the frequency of these complications . Patients who required a double-lumen HC for ( 1 ) bone marrow or peripheral blood progenitor cell transplantation or ( 2 ) intensive combination chemotherapy for haematological malignancies were r and omised to receive twice-weekly flushes of either urokinase ( 5000 units ) or heparin ( 50 units ) . HC-survival analysis was determined by Cox regression . 100 patients were enrolled ( urokinase=52 ; heparin=48 ) and treated for a mean of 8.5 weeks . No significant difference was observed in the incidence of HC-associated septicaemic events , which occurred in 8/52 in the urokinase group and 9/48 in the heparin group ( actuarial incidence 20 % versus 25 % , P=0.50 ) . Similarly , there was no differences in the incidence of exit site infections ( urokinase=27/52 and heparin=28/48 , P=0.122 ) ; HC-septic thromboses ( urokinase=2/52 and heparin=4/48 , P=0.34 ) ; lumen occlusion ( urokinase=30/52 and heparin=30/48 , P=0.681 ) ; or venous thrombosis ( urokinase=8/52 and heparin=6/48 , P=0.726 ) . Overall , a high incidence of HC-related complications was seen in both groups ; 40/52 in the urokinase group and 40/48 in the heparin group ( actuarial incidence 80 % versus 90 % , P=0.367 ) . Despite this only 18 % of HC required early removal due to complications ( urokinase=8 , heparin=10 ) . There was no difference in the incidence of complications in patients undergoing transplantation ( n=68 ) compared with chemotherapy alone ( n=32 ) . Patients with haematological malignancies were more likely to have HC-related infective complications ( P=0.006 ) , and patients with solid tumours more likely to have venous thrombosis ( P=0.027 ) . The cumulative incidence of HC-related complications in this prospect i ve study was higher than in previously reported series . Urokinase did not appear effective in reducing the frequency of these complications In this prospect i ve , r and omized , controlled , unblinded study , we compared colonization rates of a st and ard , unimpregnated central venous catheter ( CVC ) with rates for silver-coated and chlorhexidine-silversulfadiazine (CH-SS)-impregnated CVC . Patient characteristics , CVC insertion site , indwelling time , and colonization detected by semiquantitative and quantitative microbiologic techniques were documented . Two-hundred-seventy-five critically ill patients were included into the study protocol . One-hundred-sixty st and ard , 160 silver (S)-coated , and 165 externally impregnated CH-SS CVC were inserted . There was a significant difference in CVC colonization rates among study groups ( P = 0.029 ) . There was no difference in the colonization rate and the colonization per 1000 catheter days between st and ard and S-coated ( P = 0.564 ; P = 0.24 ) or CH-SS-coated CVC ( P= 0.795 ; P = 0.639 ) . When comparing antiseptic CVC with each other , colonization rates were significantly less with CH-SS-impregnated than with S-coated CVC ( 16.9 % versus 7.3 % ; P = 0.01 ; 18.2 versus 7.5 of 1000 catheter days ; P = 0.003 ; relative risk , 0.43 ; 95 % confidence interval , 0.21–0.85 ) . Whereas st and ard and S-coated CVC were first colonized 2 and 3 days after insertion , respectively , CH-SS CVC were first colonized only after 7 days . In conclusion , antiseptic-impregnated CVC could not prevent catheter colonization when compared with st and ard polyurethane catheters in a critical care setting with infrequent catheter colonization rates and CVC left in place for > 10 days Tinzaparin offers some advantages over unfractionated heparin ( UFH ) for hemodialysis circuit anticoagulation . No study has compared these two molecules as hemodialysis catheter locks . This study aim ed to compare the efficacy of tinzaparin and UFH as locks for hemodialysis tunnelled central venous catheter in patients with end-stage renal disease ( ESRD ) . A r and omized , prospect i ve , single-blinded , controlled study was undertaken . Patients were r and omly assigned to receive UFH and tinzaparin for two 7-week periods in a crossover fashion . The doses used were 5,000 U of UFH and 2,000 U of tinzaparin per catheter line . The primary outcome was the need for thrombolytic catheter lock use defined with the Hemodialysis Unit alteplase protocol . Forty-two patients with ESRD were enrolled , totalling 815 UFH lock sessions and 729 tinzaparin lock sessions . A 47.4 % reduction in the incidence of alteplase lock use was observed with tinzaparin lock ( 3.16 % vs. 6.01 % , chi-square , p = 0.0078 ) . There was no significant difference in the time to first alteplase use between the two locks by Kaplan-Meier survival analysis ( logrank , p = 0.0900 ) . Our results suggest that tinzaparin could be an appropriate alternative for a hemodialysis tunnelled central venous catheter lock , but these results should be confirmed with a larger trial The use of central venous catheters , while advantageous , is associated with a range of complications including thrombosis and infection . These complications can pose significant physical and financial costs to the patient and health care system . A critical appraisal of the two r and omized controlled trials examining this topic in critically ill patients has shown that heparin-bonded central venous catheters significantly reduced the incidence of catheter-related thrombosis and infection in children and adults . These findings suggest that heparin-bonded central venous catheters should be considered for routine use in critically ill patients A r and omized trial was conducted to assess the effect of leaving heparin locks in place longer than 72 hours . Three hundred and one patients were r and omly assigned to one of two groups . Group A had the lock changed every 72 hours and Group B had the lock left in place up to 168 hours . Due to withdrawals following r and omization , Group A contained 116 subjects and Group B 140 subjects . No significant differences were found between the two groups in relation to age , sex , medical condition , drug used , entries into the lock , minor complications , or incidence of phlebitis . The findings suggest that consideration could be given to extending insertion time up to 96 hours and possibly up to 118 hours A prospect i ve trial was carried out to test the hypothesis that therapy with intravenous ( IV ) heparin sodium reduces the incidence of thrombotic complications related to the use of central venous catheters for parenteral nutrition . The patients studied were r and omly allocated either to a group given heparin sodium , at a dosage of 5,000 IU/6 hr , or to a control group that received no heparin prophylaxis . The heparin group comprised 23 catheter periods ( 22 patients ) , and the control group 26 catheter periods ( 25 patients ) . In five of the 23 catheters in te heparin group and 14 of the 26 in the control group , catheter phlebography revealed thrombus formation in association with the catheter when this was removed . The results indicated that the use of IV heparin as prophylaxis against thrombosis reduced the risk of thrombus formation on the central venous catheter OBJECTIVE To compare the ability of normal versus heparinized saline infusion to maintain patency of the radial artery catheter used for monitoring or multiple blood sampling . DESIGN R and omized double-blind trial . SETTING A university-affiliated hospital . PATIENTS All 108 patients admitted to the surgical intensive care unit who required radial arterial line catheters . Excluded were patients who required emergency admission , those who refused to give consent , those who needed anticoagulants , thrombolytic or platelet therapy , those whose cannulation site was other than the radial artery , inadvertent discontinuation of the arterial line or incomplete data collection . This result ed in a sample of 78 adults , r and omized according to date of admission . INTERVENTIONS Forty patients admitted on odd-numbered date s received heparinized normal saline ( 2 units/mL ) , and 38 patients admitted on even date s received normal saline , both as continuous flush solutions . MAIN OUTCOME MEASURES Measurement of radial artery flow and pressure before and after cannulation , and catheter patency during cannulation . RESULTS The type of flush solution did not adversely affect the radial artery or the h and in any measurable way . Catheter blockage occurred in three patients receiving heparinized saline and seven patients receiving normal saline as the flush solution ( p = 0.06 ) . At 96 hours of cannulation , 92 % of the catheters in the heparinized saline group were patent compared with 74 % in the normal saline group . Intra-arterial blood pressure was inaccurate compared with the brachial cuff pressure in 6 patients in the heparinized saline group compared with 14 patients in the normal saline group ( p < 0.03 ) . CONCLUSIONS There is no significant difference between flushing with normal saline and heparinized saline in the maintenance of radial arterial line patency . However , the use of a continuous heparinized flush solution in pressurized arterial lines is beneficial in that it results in greater accuracy of blood pressure monitoring than normal saline infusion Background : Thrombotic occlusion is a frequent complication of central venous catheters used to provide temporary blood access on hemodialysis therapy . Heparin-lock is conventionally used to maintain patency of the catheter , but the necessity of heparin-lock has not been determined yet . Methods : After the immobilized-urokinase double-lumen central venous catheter was inserted into 48 Japanese hemodialysis patients , 22 patients r and omized to the heparin group received a 20-ml saline-flush , followed by 2 ml of 1,000 U/ml heparin-lock , and 26 patients r and omized to the saline group received only the 20-ml saline-flush once a day for each lumen . Results : Thrombotic occlusion was observed in only 1 out of 22 patients in the heparin group and 1 out of 26 patients in the saline group . No significant difference of the catheter survival was observed between the two groups ( p = 0.8599 ) . Conclusions : Natural saline-flush is sufficient for maintaining the patency of an immobilized-urokinase double-lumen central venous catheter OBJECTIVE To test the hypothesis that the continuous infusion of papaverine-containing solutions in peripheral arterial catheters would decrease the catheter failure rate and increase the functional duration of the catheter in neonates . STUDY DESIGN In a prospect i ve , r and omized , placebo-controlled , masked trial , 82 catheters were placed in 70 neonates in the papaverine group and 98 catheters were placed in 71 neonates in the placebo group . RESULTS The catheters in the papaverine group remained functional for a significantly longer duration than those in the placebo group . The median ( 25th% , 75th% ) time before catheter failure was 16.6 ( 9.5 , 24.3 ) days in the papaverine group and 12 days ( 6.1 , 18.2 ) in the placebo group ( P = .023 ; Cox proportional hazards model ) . There was no significant difference in the incidence of intraventricular hemorrhage ( IVH ) between groups , and there was no evidence of hepatic toxicity . CONCLUSIONS The continuous infusion of papaverine-containing fluids prolongs the patency of peripheral arterial catheters in neonates . In this small number of infants , we found no difference in the incidence of IVH or hepatic toxicity In a r and omized , double-blind , controlled study , we compared heparinized and nonheparinized infusions for the maintenance of perioperative arterial catheter patency and the incidence of subsequent radial arterial occlusion . Two-hundred patients were r and omized into 2 groups to receive heparinized ( group H , n = 100 ) or nonheparinized ( group S , n = 100 ) flush solutions . Radial and ulnar blood flows were assessed using Doppler probe and pulse oximetry before , just after , and 24 h after decannulation by the same investigator . The cannulation site was examined for complications such as hematoma , nerve injury , and infection . The mean duration of cannulations was 378 ± 159.0 min in group H and 332 ± 154.6 min in group S. The mean number of corrective interventions caused by dampening of the pressure wave ( mean number of positional changes [ group S , 1.5 ± 2.0 ; group H , 1.4 ± 3.8 ] and mean number of manual flushes [ group S , 1.3 ± 1.7 ; group H , 1.2 ± 1.2 ] ) was not significantly different in both groups . After decannulation , partial or total occlusion developed in 20 group H patients and 16 group S patients ( not significant ) . The incidence of occlusion was correlated to the presence of hematoma at the puncture site after decannulation ( P = 0.013 ) , long duration of cannulation ( P = 0.04 ) , and age < 65 yr ( P = 0.009 ) . In conclusion , there is no significant difference between heparinized and nonheparinized flush solutions for the maintenance of perioperative radial artery catheter patency Background : Catheter-related infection ( CRI ) is associated with increased all-cause mortality and morbidity in hemodialysis patients and may be reduced by using antimicrobial lock solutions . But the safety of long-term use of antimicrobial lock still needs to be defined . Methods : Patients with a new inserted permanent tunneled cuffed hemodialysis catheter were r and omly assigned to an antibiotic lock solution of gentamicin ( 4 mg/ml ) heparin ( G group ) or heparin alone ( H group ) . Results : A total of 140 patients were enrolled in this study . CRI rates were 0.06/1,000 catheter-days for the G group versus 0.67 in the H group ( p = 0.014 ) . The risk of CRI was 10.54 higher in patients with a heparin-alone locked catheter ( p = 0.025 ) than that with gentamicin . The serum-measured gentamicin levels were very low . Conclusions : Gentamicin lock solution reduces CRI and improves catheter survival rates in hemodialysis patients . It is relatively safe in strictly catheter-restricted antibiotic lock solution therapy We prospect ively evaluated the efficacy and safety of a low concentrate citrate lock versus heparin lock in permanent single lumen hemodialysis catheters . The frequency of clot formation , complete catheter occlusion , flow problems and the use of urokinase as well as catheter infection episodes were monitored during 1370 dialysis sessions in 19 patients , r and omised in two study groups . There was a significantly higher number of dialysis sessions with clot formation in the citrate group but regarding the need for urokinase bolus or infusion , complete obstruction of the catheter or local infections , there were no statistically significant differences between groups . The higher incidence of clotting in the citrate locked catheters had no repercussion on dialysis efficiency , effective blood flow or on the use of thrombolytic therapy . We found that low concentrate citrate is as safe as heparin for long-term interdialytic anticoagulation of permanent single lumen hemodialysis catheters but is more efficient from a pharmaco-economic viewpoint PURPOSE Infection is a serious complication of central venous catheters in immunocompromised patients . Catheter-related infection may be caused by fibrin deposition associated with catheters . Interventions design ed to decrease fibrin deposition have the potential to reduce catheter-related infections . The purpose of this study was to evaluate the role of low-dose unfractionated heparin in preventing catheter-related bloodstream infection in patients with hemato-oncological disease . PATIENTS AND METHODS This study was a r and omized , controlled trial in which patients with nontunneled catheters were r and omly assigned to receive either intravenous unfractionated heparin ( continuous infusion of 100 U/kg per day ) or 50 mL/day of normal saline solution as a continuous infusion ( control group ) . Heparin was continued until the day of discharge . Catheter-related bloodstream infection was defined according to Infectious Disease Society of America guidelines . RESULTS Two hundred and eight patients were r and omly assigned . Four patients were excluded after assignment . Ultimately , 204 patients were analyzed . Catheter-related bloodstream infection occurred in 6.8 % ( 7 of 102 catheters ) of those in the heparin group ( 2.5 events per 1,000 days ) and in 16.6 % ( 17 of 102 catheters ) of those in the control group ( 6.4 events per 1,000 days ) ( P = .03 ) . No other risk factors were found for the development of catheter-related bloodstream infection . Four and five patients experienced severe bleeding in the heparin and control groups , respectively ( P = .2 ) . We did not observe heparin-induced thrombocytopenia . CONCLUSION The use of continuous infusion of low-dose unfractionated heparin ( 100 U/kg per day ) can be a practical and economical approach to the prevention of catheter-related bloodstream infection in patients with hemato-oncological disease BACKGROUND Central venous catheters are a principal source of nosocomial bloodstream infections , which are difficult to control . OBJECTIVE To determine the efficacy of catheters coated with minocycline and rifampin in preventing catheter-related colonization and bloodstream infections . DESIGN Multicenter , r and omized clinical trial . SETTING Five university-based medical centers . PATIENTS 281 hospitalized patients who required 298 triple-lumen , polyurethane venous catheters . INTERVENTION 147 catheters were pretreated with tridodecylmethyl-ammonium chloride and coated with minocycline and rifampin . Untreated , uncoated catheters ( n = 151 ) were used as controls . MEASUREMENTS Quantitative catheter cultures , blood cultures , and molecular typing of organisms to determine catheter-related colonization and bloodstream infections . RESULTS The group with coated catheters and the group with uncoated catheters were similar with respect to age , sex , underlying diseases , degree of immunosuppression , therapeutic interventions , and risk factors for catheter infections . Colonization occurred in 36 ( 26 % ) uncoated catheters and 11 ( 8 % ) coated catheters ( P < 0.001 ) . Catheter-related bloodstream infection developed in 7 patients ( 5 % ) with uncoated catheters and no patients with coated catheters ( P < 0.01 ) . Multivariate logistic regression analysis showed that coating catheters with minocycline and rifampin was an independent protective factor against catheter-related colonization ( P < 0.05 ) . No adverse effects related to the coated catheters or antimicrobial resistance were seen . An estimate showed that the use of coated catheters could save costs . CONCLUSIONS Central venous catheters coated with minocycline and rifampin can significantly reduce the risk for catheter-related colonization and bloodstream infections . The use of these catheters may save costs The aim of this study was to evaluate the administration of postoperative heparin thromboprophylaxis via an indwelling subcutaneous cannula . Fifty consecutive patients undergoing laparotomy , laparoscopy or varicose vein surgery were studied . Each patient on admission had a 24 gauge subcutaneous cannula inserted and a conventional subcutaneous heparin injection preoperatively . The first 20 patients received an alternating postoperative regimen of morning heparin via cannula and evening heparin via conventional injection into the abdominal wall . The remaining 30 patients received postoperative heparin twice daily via the cannula . Patients and nursing staff were interviewed and their preference for either method was recorded . There were no significant complications with the cannula system . Although it was more costly and nursing staff found it more labour intensive than conventional subcutaneous injections , the majority of patients preferred to receive heparin via the cannula . We conclude that this is an excellent method of administering prophylactic subcutaneous heparin , especially for patients with a strong aversion to injections Interdialytic hemodialysis catheter-locking solutions could contribute to a reduction of catheter-related complications , especially infections . However , they can cause side effects because of leakage from the tip of the catheter . Recently , trisodium citrate ( TSC ) has been advocated because of its antimicrobial properties and local anticoagulation . In a multicenter , double-blind , r and omized , controlled trial , TSC 30 % was compared with unfractionated heparin 5000 U/ml for prevention of catheter-related infections , thrombosis , and bleeding complications . The study was stopped prematurely because of a difference in catheter-related bacteremia ( CRB ; P < 0.01 ) . Of 363 eligible patients , 291 could be r and omized . The study included 98 tunneled cuffed catheters and 193 untunneled . There were no significant differences in patient and catheter characteristics on inclusion . In the heparin group , 46 % of catheters had to be removed because of any complication compared with 28 % in the TSC group ( P = 0.005 ) . CRB rates were 1.1 per 1000 catheter-days for TSC versus 4.1 in the heparin group ( P < 0.001 ) . For tunneled cuffed catheters , the risk reduction for CRB was 87 % ( P < 0.001 ) and for untunneled catheters was 64 % ( P = 0.05 ) . Fewer patients died from CRB in the TSC group ( 0 versus 5 ; P = 0.028 ) . There were no differences in catheter flow problems and thrombosis ( P = 0.75 ) . No serious adverse events were encountered . Major bleeding episodes were significantly lower in the TSC group ( P = 0.010 ) . TSC 30 % improves overall patency rates and reduces catheter-related infections and major bleeding episodes for both tunneled and untunneled hemodialysis catheters . Flow problems are not reduced A double-blind , r and omized study was conducted in 30 adult medical intensive care unit patients to determine if the presence of heparin in continuous-flush solutions prolongs the functional life span of radial arterial catheters compared with catheters flushed with solutions not containing heparin . Patients were consecutively entered into the study and r and omly assigned to receive arterial line flush solutions containing 0.9 % sodium chloride ( NSS ) or heparin 4 U/ml in 0.9 % sodium chloride . The flow rate of each flush solution was approximately 3 ml/hr . Use of the heparin-containing flush solution result ed in a catheter survival rate of 86 % at 96 hours compared with a rate of only 52 % after 40 hours with NSS ( p less than 0.05 ) . In addition , the heparin-flushed catheters required significantly less manipulation to prevent catheter occlusion and arterial pressure-wave dampening ( p less than 0.01 ) . The use of NSS as a continuous flush for radial artery catheters is associated with an increased frequency of catheter occlusion and malfunctions compared with solution containing heparin , and thus is not recommended in patients with normal coagulation status and platelet count INTRODUCTION Ethanol lock ( EL ) is used to reduce catheter infections , but its impact on dialysis catheter dysfunction has not been studied . METHODS We analyzed the rate of dialysis silicone catheter dysfunction after an interdialytic 60 % EL in an open prospect i ve controlled non crossover cohort study , with each patient being his or her own control . The study was divided into three consecutive 2-week periods : the pre- and post-intervention periods , in which interdialytic st and ard locks ( SL ) were used , and the intervention period , in which one EL was instilled during the first week , and two consecutively in the second week . We analyzed the rate of catheter dysfunction ( exchange , use of fibrinolytic , reversing the lines , difficulty in instilling or withdrawing fluid ) after EL or SL . RESULTS In 30 patients , 90 EL were instilled . The rate of catheter dysfunction increased during the EL period ( 2 - 13 % , p < 0.001 ) , and between the two consecutive dialysis sessions before and after EL ( p < 0.05 ) . It decreased between the two consecutive dialysis sessions after EL and the following dialysis session after an SL ( p < 0.05 ) . No catheter was removed . The urea reduction ratio did not differ in dialysis after an SL and after an EL ( 0.77 vs. 0.73 , p = 0.17 ) . CONCLUSION Short term EL is associated with a transient increase in catheter dysfunction , without result ing in catheter removal or decreasing dialysis efficiency The use of invasive lines with heparinized fluid for hemodynamic monitoring is a routine procedure in critical care areas . The main objective of this study was to compare the duration of patency of indwelling arterial catheter lines and patient coagulation values when the recommended dilution of 1.0 U heparin/mL was used versus the use of only 0.25 U heparin/mL. One hundred four intensive care unit ( ICU ) patients were studied . There were no significant differences between the two groups in patency or coagulation values . The results of the study demonstrated that 0.25 U heparin/mL was sufficient to maintain arterial line patency for patients with lines in place for up to 3 days Background : The objective of this study was to assess the impact of heparin concentration retained in temporary double-lumen catheters on bleeding risk . Methods : Activated partial thromboplastin time ( aPTT ) was measured in patients hemodialyzed via double-lumen catheters . Heparin solutions of 5,000 U/ml ( group 1 , n = 95 ) and 1,000 U/ml ( group 2 , n = 89 ) were r and omly retained in catheters after placement and each hemodialysis ( HD ) session . Blood transfusion , bleeding episodes , and changes of hematocrit were recorded . Results : The aPTT at the beginning of HD or 10 min after heparin lock was significantly prolonged , which was more prominent in the 5,000 U/ml group , whereas the aPTT declined to baseline values at the end of HD or before the next dialysis session in both groups . Infection and occlusion rates were similar in both groups . More patients suffered from major bleeding and prominent decline of hematocrit in the 5,000 U/ml group . Conclusions : Low-dose heparin ( 1,000 U/ml ) retention in double-lumen catheters for temporary HD maintains comparable catheter patency and might reduce the bleeding risk Heparinization of fluids ( 1 unit/ml ) infused through an umbilical artery catheter ( UAC ) was efficacious in prolonging catheter patency in a double-blind , r and omized , controlled clinical study . On the basis of life-table analysis , the half-life of catheter function was seven days in the heparinized group as compared with just over two days in the nonheparinized group ( P less than .01 ) . UAC occlusion occurred in 4 of 32 patients in the heparinized and 19 of 30 in the nonheparinized group ( chi 2 = 17.6 , P less than .01 ) . Blood transfusions , number of arterial blood gases drawn through the UACs , and fluid infusion rates were not related to catheter occlusion . Heparinization of the UAC infusion did not alter the partial thromboplastin time or the incidence of catheter-related thromboembolic phenomena in the extremities . Heparinization of fluids infused through a UAC appears to be useful in the care of critically ill neonates BACKGROUND Continuous renal replacement therapy ( CRRT ) has been increasingly used in critically ill patients with acute kidney injury ( AKI ) . One of the major properties that likely influence the catheter lifespan includes its surface specificity . We hypothesized that the improvement of blood-surface interaction by a reactive polymer film coating might reduce thrombogenic events in the vascular access device and subsequently lead to prolonged catheter survival in this clinical setting . METHODS We compared , in a r and omized study , the clinical application of two temporary catheters ( TCs ) : one surface-modified double-lumen catheter ( smDLC ) and one st and ard sDLC with identical geometry and flow design . Efficacy end points were defined as the ability to complete at least 72 h CRRT without interruption due to TC dysfunction and ability to achieve blood flow rates of ≥150 mL/min . Safety end points were defined as the occurrence of catheter-related ( CR ) bacteraemia or other CR complications . RESULTS We evaluated 236 critically ill patients ( 264 TCs ) with AKI on CRRT ( continuous venovenous haemodiafiltration ) with age ( mean±SD ) of 56.9±17.9 years . The clinical investigation revealed that the number of hours before TC removal according to clinical requirements was significantly higher with smDLC as compared with sDLC ( 131±38 vs 113±21 h ; P=0.004 ) . Temporary catheter dysfunction occurred in 5 % for smDLC and 14 % for sDLC ; P=0.001 . Thrombosis of smDLC and sDLC was observed in 2.3 episodes per 1000 TC-days [ 95 % confidence interval ( CI ) , 1.9 - 2.5 ] and 4.2 episodes per 1000 TC-days ( 95 % CI , 4.0 - 4.4 ) , respectively ; P=0.021 . The blood flow rate was 221±29 mL/min vs 187±36 mL/min for smDLC and sDLC , respectively ; P=0.012 . Compared with the overall mean of TC dysfunction or thrombosis , the relative risk of premature removal ( < 72 h ) was 0.43 ( 95 % CI , 0.13 - 0.98 ; P=0.041 ) for smDLC and 2.51 ( 95 % CI , 1.04 - 9.22 ; P=0.034 ) for sDLC with a significantly higher catheter-related bacteraemia rate in this latter group ( P=0.008 ) . CONCLUSION Micropatterned surface coating with a polyurethane polymer significantly increased TC survival with lower dysfunction rate , lower thrombotic events and better bacteriological barrier than sDLC in critically ill patients with AKI necessitating CRRT BACKGROUND AND AIM In Mainl and China , heparin saline solution is commonly used for flushing and locking peripheral intravenous access devices in clinical practice for a long time . We conducted a prospect i ve controlled trial to compare the effectiveness and safety of preservative-free 0.9 % sodium chloride solution versus heparin saline solution as flushing and locking solution for peripheral intravenous access devices . METHODS Patients with gastroenterological or hepatic diseases were enrolled for this study from August 2011 to October 2011 . After non-r and omized allocation , preservative-free 0.9 % sodium chloride was used as flushing and locking solution in the sodium chloride solution group , while hepatic solution ( 10 U/mL ) was given in the heparin saline solution group . The device related complications and its maintenance duration were compared between two groups . One-way ANOVA , Chi(2 ) , or Mantel-Haenszel test were performed using SPSS 13.0 and RevMan 5.0 . RESULTS Totally , 181 and 178 peripheral intravenous access devices in the sodium chloride solution and heparin saline solution groups were included and analyzed . Results indicated than sodium chloride solution did not increase the risks of occlusion ( 7.7 % vs. 7.9 % ) and other adverse events of peripheral intravenous access devices ( P = 0.163 ) . Sodium chloride solution neither shortened the duration of peripheral intravenous access devices maintenance ( 3.6 ± 1.1 days vs. 3.7 ± 1.2 days , P = 0.651 ) , nor increased the proportion of abnormal withdrawal ( 29.3 % vs. 31.5 % , P = 0.654 ) . CONCLUSION Sodium chloride solution is as effective and safe as conventional heparin saline solution for flushing and locking peripheral intravenous access devices , which results from our evidence -based study and should be transferred to other nurses in China Objective : To compare the effects of heparin or sodium citrate used to anticoagulate indwelling arterial catheters on acid‐base and electrolyte measurements . Design : R and omized controlled trial . Setting : Medical‐surgical university‐affiliated intensive care unit . Subjects : Twenty patients with indwelling arterial catheters . Interventions : Patients were r and omly allocated to have ten 1‐mL aliquots of blood sample d serially from an arterial catheter maintained with either heparin or sodium citrate . A sample then obtained by arterial puncture provided true measurement values . Acid‐base and electrolyte measurements of whole blood were obtained from each sample by means of a Corning 860 analyzer . Measurements and Main Results : Contamination with sodium citrate lowered ionized calcium and pH but increased glucose and PCO2 . Heparin produced negligible effects on those measurements . When sodium citrate was used , reliable measurements were not obtained for ionized calcium , pH , and glucose , even after 9 mL of blood had been discarded . However , reliable PCO2 measurements were obtained after 2 mL of blood was discarded . Conclusions : Sodium citrate used to maintain arterial catheters can contaminate blood sample s. The result of that contamination can mimic severe hypocalcemia , metabolic acidosis , and mild hyperglycemia . Failure to recognize the effects of sodium citrate on acid‐base and electrolyte measurements may lead to changes in treatment that could affect patient outcome adversely Central venous access devices are often essential for the administration of chemotherapy to patients with malignancy , but its use has been associated with a number of complications , mainly thrombosis . The true incidence of upper extremity deep vein thrombosis ( DVT ) in this setting is difficult to estimate since there are very few studies in which DVT diagnosis was based on objective tests , but its sequelae include septic thrombophlebitis , loss of central venous access and pulmonary embolism . We performed an open , prospect i ve study in which all cancer patients who underwent placement of a long-term Port-a-Cath ( Pharmacia Deltec Inc ) subclavian venous catheter were r and omized to receive or not 2500 IU sc of Fragmin once daily 90 days . Venography was routinely performed 90 days after catheter insertion , or sooner if DVT symptoms had appeared . Our aims were : 1 ) to investigate the effectiveness of low doses of Fragmin in preventing catheter-related DVT ; and 2 ) to try to confirm if patients with high platelet counts are at a higher risk to develop subclavian DVT , as previously suggested . On the recommendation of the Ethics Committee , patient recruitment was terminated earlier than planned : DVT developed in 1/16 patients ( 6 % ) taking Fragmin and 8/13 patients ( 62 % ) without prophylaxis ( Relative Risk 6.75 ; 95 % CI : 1.05 - 43.58 ; p = 0.002 , Fisher exact test ) . No bleeding complications had developed . As for prediction of DVT , there was a tendency towards a higher platelet count in those patients who subsequently developed DVT , but differences failed to reach any statistical significance ( 286 + /- 145 vs 207 + /- 81 x 10(9)/1 ; p = 0.067 ) . According to our experience , Fragmin at the dosage used proved to be both effective and safe in these patients OBJECTIVE The purpose of this study was to evaluate whether a valved peripherally inserted central catheter ( PICC ) design would result in a lower incidence of occlusion , infection , and malfunction than a clamped catheter . SUBJECTS AND METHODS Three hundred sixty-two study patients ( 233 men , 129 women ; mean age , 44 years ) were r and omized to receive a clamped ( n = 182 ) or valved ( n = 180 ) 5-French single-lumen PICC . Catheters were placed under fluoroscopic ( n = 331 ) or sonographic guidance ( n = 31 ) . The valved PICC was flushed with saline solution , and the clamped PICC was flushed with a heparin-saline solution . All patients were prospect ively followed up at least weekly for catheter status and complications . RESULTS Percutaneous placement with the catheter tip in the central veins was successful in 99 % of patients . Mean dwell time was 34 days . Twenty-six occlusive or infectious complications occurred in the clamped catheter group and 12 in the valved catheter group ( p = .02 ) . The clamped and valved catheter groups had 13 and five occlusions , respectively ( p = .06 ) , and 12 and five catheter-related blood stream infections , respectively ( p = .09 ) . Most occlusions ( 68 % ) were treated successfully with urokinase , and site infection or sepsis was treated by catheter removal . CONCLUSION We found a statistically significant difference in the complication rate for the valved PICC compared with the clamped PICC . With the valved PICC , occlusion and infection were reduced , and patients having these catheters did not require heparin flushes OBJECTIVE : To determine whether heparin sodium , when added to fluids infused through a peripheral catheter , reduces some local catheter-related problems ( i.e. , phlebitis , catheter obstruction , and extravasation of fluid ) and extends the catheter 's useful life . DESIGN : Prospect i ve , double-blind , placebo-controlled . SETTING : Internal medicine ward of a general hospital with 400 beds . PATIENTS : Eighty-one consecutive acute collaborating patients who had a venous catheter in the forearm , inserted by nurses with more than one year of professional experience . INTERVENTION : Heparin sodium 1000 units/mL or NaCl 0.9 % was added to compatible infusion fluids just before they were given to the patients . The final concentration of heparin was 1 unit/mL. MEASUREMENTS : Length of time until catheters were removed and reasons for their removal . RESULTS : The heparin group had a lower rate of local catheter-related problems than the placebo group ( 34.3 vs. 61.5 percent , respectively , p<0.05 ; 95 percent confidence interval for the difference 4.3 to 50.1 percent ) . The catheter 's mean life in the heparin group was longer than that of the placebo group ( 98.9 ± 55.2 vs. 66.2 ± 47.2 h , respectively , p<0.05 ; 95 percent confidence interval for the difference 9.15 to 56.25 h ) . This effect was mainly attributable to prevention of noninflammatory catheter-related problems ( e.g. , obstruction , extravasation ) and to a delay in the appearance of phlebitis . CONCLUSIONS : Heparin sodium , when added to infusion fluids to a final concentration of 1 unit/mL , diminishes local intravenous catheter-related problems and extends the catheter 's life Purpose This study was undertaken to determine if central venous catheter (CVC)-related infection in children with cancer could be prevented by monthly flushing of the catheter with urokinase . Patients and Methods Between August 1994 and July 1998 , 103 patients with cancer were r and omized at the time of subcutaneous CVC placement to receive monthly flushing of their catheters with either 5000 IU of urokinase – heparin or heparin alone . Patients subsequently had blood cultures taken from their CVCs during an episode of fever . Results Seventy-four of the 103 patients ( 72 % ) enrolled in the study received at least 6 catheter flushes : 40 with urokinase – heparin and 34 with heparin . The median number of flushes was 9.5 in the urokinase – heparin group and 10.2 in the heparin-only group ( P = 0.62 ) . There were 5 positive blood cultures in the urokinase – heparin group and seven in patients receiving heparin alone ( P = 0.27 ) . Staphylococcus epidermidis was isolated from the blood of 3 patients receiving urokinase – heparin and 6 in those receiving heparin alone ( P = 0.17 ) . Conclusion Prophylactic monthly catheter flushes with 5000 IU urokinase did not significantly decrease the number of documented bacteremic events in children with cancer who have CVCs Objective To compare heparin sodium ( 100 United States Pharmacopeia U/mL ) with 0.9 % sodium chloride for use in the maintenance of intermittent intravenous ( IV ) devices during pregnancy . Methods Women at 26–34 weeks ' gestation who required serial phlebotomy were assigned r and omly to heparin or normal saline flush , administered in a double-blind fashion . Catheter sites were examined and flushed with the study solution at least once every 6 hours . Partial thromboplastin times ( PTTs ) were measured at catheter insertion and 48 hours later . Statistical analysis was performed with Student t test , Mann-Whitney U test , Fisher exact test , log-rank , and χ2 analysis , as appropriate . Results There was a significant increase in catheter patency rate at 48 and 72 hours in the heparin group ( 26 of 31 versus 17 of 33 , and 21 of 31 versus nine of 33 , respectively ; P < .01 ) . In addition , there was a significantly lower rate of catheter complications in the heparin group ( four of 31 versus 13 of 33 ; P < .01 ) . There were no differences in PTTs . Conclusion During pregnancy , dilute heparin flush to maintain patency of intermittent IV site devices results in the following : a greater catheter patency rate at 48 and 72 hours after insertion of the catheter , a lower rate of catheter complications requiring therapy , and no alteration in PTT In ICU setting s arterial catheters ( AC ) are used to manage critically ill patients . Maintaining the patency of these catheters is important for continuous hemodynamic evaluation and therapeutic adjustment . Heparinized solutions are used for this purpose although the increasing literature describes the use of saline solutions for the same reason . The authors compare the use of heparinized versus saline solution in the maintenance of ACs and to detect changes in aPTT , platelet count , and local inflammatory signs , in a double-blind r and omized trial INTRODUCTION Intravenous ( i.v . ) therapy may be associated with important catheter-related morbidity and discomfort . The safety , efficacy , comfort , and cost-effectiveness of peripherally inserted central catheters ( PICCs ) were compared to peripheral catheters ( PCs ) in a r and omized controlled trial . METHODS Hospitalized patients requiring i.v . therapy > or= five days were r and omized 1:1 to PICC or PC . Outcomes were incidence of major complications , minor complications , efficacy of catheters , patient satisfaction , and cost-effectiveness . RESULTS 60 patients were included . Major complications were observed in 22.6 % of patients in the PICC group [ six deep venous thrombosis ( DVT ) , one insertion-site infection ] and 3.4 % of patients in the PC group [ one DVT ; risk ratio ( RR ) 6.6 ; P = 0.03 ] . Superficial venous thrombosis ( SVT ) occurred in 29.0 % of patients in the PICC group and 37.9 % of patients in the PC group ( RR 0.60 ; P = 0.20 ) . Patients in the PICC group required 1.16 catheters on average during the study period , compared with 1.97 in the PC group ( P < 0.04 ) . The mean number of venipunctures ( catheter insertion and blood sampling ) was 1.36 in the PICC group vs. 8.25 in the PC group ( P < 0.001 ) . Intravenous drug administration was considered very or quite satisfying by 96.8 % of the patients in the PICC group , and 79.3 % in the PC group . Insertion and maintenance mean cost was 690 US$ for PICC and 237 US$ for PC . DISCUSSION PICC is efficient and satisfying for hospitalized patients requiring i.v . therapy > or= five days . However , the risk of DVT , mostly asymptomatic , appears higher than previously reported , and should be considered before using a PICC BACKGROUND Evidence is needed on the best solution for flushing central venous catheters . OBJECTIVE To underst and current flushing practice s for short-term central venous catheters among critical care nurses before implementation of a r and omized , controlled trial comparing physiological saline with heparin solution for flushing to maintain catheter patency . METHODS A 6-item survey including demographic data was mailed to 2000 practicing critical care nurses in the United States . An additional 316 surveys were completed at the annual conference of the American Association of Critical-Care Nurses . RESULTS Most ( 71.5 % ) of the 632 respondents who completed the survey were staff nurses . Most respondents ( 64.6 % ; 95 % CI , 60.86%-68.34 % ) reported using physiological saline exclusively to flush central venous catheters and maintain patency . For heparin-containing solutions , the concentration and volume used varied . The most commonly reported volumes for flushing were 10 mL for saline ( 63 % ; 95 % CI , 59.18%-66.82 % ) and 3 mL for heparin ( 50.2 % ; 95 % CI , 43.5%-56.9 % ) . CONCLUSION Flushing practice s for central venous catheters vary widely . A r and omized controlled trial is needed to determine the optimal flushing solution to maintain short-term patency Abstract Background : Locking catheter with heparin may increase bleeding risk of some hemodialysis ( HD ) patients . Hence , the security and effectivity of 10 % concentrated sodium chloride ( CSC ) used as an alternative method for patients with high bleeding risk need to be investigated . Methods : Seventy-two patients inserted temporary central venous catheters were divided into two groups r and omly . A total of 3125 U/mL heparin saline ( HS ) was used in HS group and 10 % CSC in CSC group to lock catheters . Heparin-free HD was used for the first time and plasma specimens were collected to test coagulation indicators before catheter-locking ( at the end of HD ) and at 30 min after it . Then , blood flow velocities ( BFVs ) , incidences of catheter thrombosis , etc . were followed up at each time of HD . Results : Activated partial thromboplastin time ( APTT ) of two groups had no difference at the end of heparin-free HD ( 27.100 [ 25.675–28.950 ] vs. 27.250 [ 25.150–29.575 ] second , p = 0.933 ) , but at 30 minutes after using different catheter lock solutions , APTT of HS group was obviously longer than CSC group ( 50.100 [ 41.275–65.400 ] vs. 27.500 [ 25.525–29.875 ] second , p < 0.001 ) . Catheters ’ retaining time of two groups were the same ( p = 0.306 ) , so did the average BFVs ( p > 0.05 ) . But catheters ’ thrombosis incidence and urokinase usage of HS group were less than CSC group ( p < 0.05 ) . Conclusion : Comparing with HS group , thrombosis incidences of CSC group increased , but catheters ’ retaining time and average BFVs remained the same and coagulation indicators of it were unaffected . Therefore , it can be an effective alternative lock method for HD patients with high bleeding risk Purpose The objective of this study was to compare the initial safety and efficacy of a novel 30 % ethanol/4 % sodium citrate catheter-locking solution to heparin in a hemodialysis population . Methods This was a prospect i ve , r and omized , pilot study of 40 hemodialysis patients r and omized to a 30 % ethanol/4 % sodium citrate or heparin 1000 units/mL locking solution . The primary outcome was identification of any serious adverse events over the study duration . Secondary outcomes included the rate per 1000 catheter days for catheter-related bloodstream infections ( CRBSI ) , alteplase use , catheter dysfunction , and catheter removal . Results Three serious adverse events were reported as possibly related to the catheter solutions . Only one CRBSI was observed during the study in the heparin arm . The rate of alteplase use was 1.5/1000 catheter days in the heparin arm compared to 2.8/1000 catheter days in the ethanol/citrate arm ( rate ratio = 1.85 , 90 % CI 0.48 , 7.07 , p value = 0.45 ) , while the rate of catheter dysfunction was 6.8/1000 catheter days in the heparin arm compared to 1.9/1000 catheter days in the ethanol citrate arm ( rate ratio = 0.27 , 90 % CI 0.10 , 0.74 , p value = 0.04 ) . Catheter survival to first catheter outcome was longer in the ethanol/citrate group compared to heparin and there were no catheter removals due to bacteremia or thrombosis . Conclusions The ethanol/sodium citrate locking solution was safely used in this study . It appears to prevent CRBSI and may improve catheter survival compared to heparin . Trial registration Clinical Trials.gov Identifier : NCT01394458 |
12,923 | 30,697,157 | The study highlighted the importance of using st and ard protocol s to evaluate executive dysfunction in Alzheimer 's disease .
The Stroop task allows discriminating better between healthy and pathological aging | Alzheimer 's disease is a severe irreversible syndrome , characterized by a slow and progressive cognitive decline that interferes with the st and ard instrumental and essential functions of daily life .
Promptly identifying the impairment of particular cognitive functions could be a fundamental condition to limit , through preventive or therapeutic interventions , the functional damages found in this degenerative dementia .
This study aims to analyse , through a systematic review of the studies , the sensitivity of four experimental paradigms ( Wisconsin Card Sorting Test , Stroop Task , Go/No-Go Task , and Flanker Task ) considered as golden st and ard instruments for executive functions assessment in elderly subjects affected by Alzheimer dementia . | Heterogeneity of executive tasks has made it difficult to determine whether there are age-related declines in executive functioning . To address this issue , 112 individuals , 20 - 79 years old , took the California Trail Making Test ( CTMT ) and the California Stroop Test ( CST ) , subtests of the Delis-Kaplan Executive Function Scale ( D. C. Delis , E. Kaplan , & J. H. Kramer , in press ) that include measurement of component skills embedded in the executive function tasks . Multiple regression analyses revealed that after controlling for component skills , age had a significant effect on the executive requirement of the CST , namely speed on the interference condition . Age did not affect switching performance on the letter-number condition of the CTMT . Additional analyses revealed that age was significantly associated with commission of certain types of errors . This study confirms the importance of partialing out components in the assessment of multidimensional cognitive tasks , particularly when making age comparisons . It also emphasizes specificity over generalizability when examining the impact of age on cognition BACKGROUND Subjects with a mild cognitive impairment ( MCI ) have a memory impairment beyond that expected for age and education yet are not demented . These subjects are becoming the focus of many prediction studies and early intervention trials . OBJECTIVE To characterize clinical ly subjects with MCI cross-sectionally and longitudinally . DESIGN A prospect i ve , longitudinal inception cohort . SETTING General community clinic . PARTICIPANTS A sample of 76 consecutively evaluated subjects with MCI were compared with 234 healthy control subjects and 106 patients with mild Alzheimer disease ( AD ) , all from a community setting as part of the Mayo Clinic Alzheimer 's Disease Center/Alzheimer 's Disease Patient Registry , Rochester , Minn. MAIN OUTCOME MEASURES The 3 groups of individuals were compared on demographic factors and measures of cognitive function including the Mini-Mental State Examination , Wechsler Adult Intelligence Scale-Revised , Wechsler Memory Scale-Revised , Dementia Rating Scale , Free and Cued Selective Reminding Test , and Auditory Verbal Learning Test . Clinical classifications of dementia and AD were determined according to the Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer 's Disease and Related Disorders Association criteria , respectively . RESULTS The primary distinction between control subjects and subjects with MCI was in the area of memory , while other cognitive functions were comparable . However , when the subjects with MCI were compared with the patients with very mild AD , memory performance was similar , but patients with AD were more impaired in other cognitive domains as well . Longitudinal performance demonstrated that the subjects with MCI declined at a rate greater than that of the controls but less rapidly than the patients with mild AD . CONCLUSIONS Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD . They appear to constitute a clinical entity that can be characterized for treatment interventions Deficits in visual cognition in Alzheimer 's disease ( AD ) arise from neuropathological changes in higher-order association areas of the cortex and from defective input from lower-level visual processing areas . We investigated whether enhanced signal strength may lead to improvement of visual cognition in AD . We tested 35 individuals with probable AD , 35 age-matched elderly control ( EC ) and 58 young control ( YC ) adults on letter identification , word reading , picture naming , discrimination of unfamiliar faces , and pattern completion . The contrast sensitivity step-difference across an independent sample of AD and EC groups was used in calculating an image filter , from which we produced stimulus-strength conditions of low-de grade d , medium-normal , and high-enhanced . Using this filter we created a hypothetical proximal-strength equivalence between AD at medium strength and EC at low strength , and between AD at high strength and EC at medium strength . For letter identification , word reading , picture naming , and face discrimination , medium strength elicited AD accuracy levels and reaction times that were similar to those of EC at low strength . On picture naming , increased strength reduced perceptual-type errors for EC and AD and r and om errors for AD . For word reading , high strength elicited AD accuracy levels and reaction times that were equivalent to those of EC at medium strength . We saw no effect of signal-strength manipulation on performance of pattern completion , possibly owing to the complex cognitive dem and s of that task or to the inadequacy of the filter for its images . The results indicate that putative AD-EC differences in cognition directly reflect contrast sensitivity differences between the groups . Enhancement of stimulus strength can ameliorate vision-based deficits and lead to improvement in some aspects of cognitive performance . These results suggest new non-pharmacological avenues to explore in the attempt to improve cognition in elderly adults and especially in individuals with AD This individual differences study examined the separability of three often postulated executive functions-mental set shifting ( " Shifting " ) , information updating and monitoring ( " Updating " ) , and inhibition of prepotent responses ("Inhibition")- and their roles in complex " frontal lobe " or " executive " tasks . One hundred thirty-seven college students performed a set of relatively simple experimental tasks that are considered to predominantly tap each target executive function as well as a set of frequently used executive tasks : the Wisconsin Card Sorting Test ( WCST ) , Tower of Hanoi ( TOH ) , r and om number generation ( RNG ) , operation span , and dual tasking . Confirmatory factor analysis indicated that the three target executive functions are moderately correlated with one another , but are clearly separable . Moreover , structural equation modeling suggested that the three functions contribute differentially to performance on complex executive tasks . Specifically , WCST performance was related most strongly to Shifting , TOH to Inhibition , RNG to Inhibition and Updating , and operation span to Updating . Dual task performance was not related to any of the three target functions . These results suggest that it is important to recognize both the unity and diversity of executive functions and that latent variable analysis is a useful approach to study ing the organization and roles of executive functions BACKGROUND Modifiable vascular and lifestyle-related risk factors have been associated with dementia risk in observational studies . In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability ( FINGER ) , a proof-of-concept r and omised controlled trial , we aim ed to assess a multidomain approach to prevent cognitive decline in at-risk elderly people from the general population . METHODS In a double-blind r and omised controlled trial we enrolled individuals aged 60 - 77 years recruited from previous national surveys . Inclusion criteria were CAIDE ( Cardiovascular Risk Factors , Aging and Dementia ) Dementia Risk Score of at least 6 points and cognition at mean level or slightly lower than expected for age . We r and omly assigned participants in a 1:1 ratio to a 2 year multidomain intervention ( diet , exercise , cognitive training , vascular risk monitoring ) , or a control group ( general health advice ) . Computer-generated allocation was done in blocks of four ( two individuals r and omly allocated to each group ) at each site . Group allocation was not actively disclosed to participants and outcome assessors were masked to group allocation . The primary outcome was change in cognition as measured through comprehensive neuropsychological test battery ( NTB ) Z score . Analysis was by modified intention to treat ( all participants with at least one post-baseline observation ) . This trial is registered at Clinical Trials.gov , number NCT01041989 . FINDINGS Between Sept 7 , 2009 , and Nov 24 , 2011 , we screened 2654 individuals and r and omly assigned 1260 to the intervention group ( n=631 ) or control group ( n=629 ) . 591 ( 94 % ) participants in the intervention group and 599 ( 95 % ) in the control group had at least one post-baseline assessment and were included in the modified intention-to-treat analysis . Estimated mean change in NTB total Z score at 2 years was 0·20 ( SE 0·02 , SD 0·51 ) in the intervention group and 0·16 ( 0·01 , 0·51 ) in the control group . Between-group difference in the change of NTB total score per year was 0·022 ( 95 % CI 0·002 - 0·042 , p=0·030 ) . 153 ( 12 % ) individuals dropped out overall . Adverse events occurred in 46 ( 7 % ) participants in the intervention group compared with six ( 1 % ) participants in the control group ; the most common adverse event was musculoskeletal pain ( 32 [ 5 % ] individuals for intervention vs no individuals for control ) . INTERPRETATION Findings from this large , long-term , r and omised controlled trial suggest that a multidomain intervention could improve or maintain cognitive functioning in at-risk elderly people from the general population . FUNDING Academy of Finl and , La Carita Foundation , Alzheimer Association , Alzheimer 's Research and Prevention Foundation , Juho Vainio Foundation , Novo Nordisk Foundation , Finnish Social Insurance Institution , Ministry of Education and Culture , Salama bint Hamdan Al Nahyan Foundation , Axa Research Fund , EVO funding for University Hospitals of Kuopio , Oulu , and Turku and for Seinäjoki Central Hospital and Oulu City Hospital , Swedish Research Council , Swedish Research Council for Health , Working Life and Welfare , and af Jochnick Foundation Objectives To provide estimates of survival after onset of dementia by age , sex , self reported health , disability , and severity of cognitive impairment . Design Analysis of participants from prospect i ve population based cohort study in 1991 - 2003 , with follow-up of dementia status in all individuals after two and six years ( in one centre ) and 10 years and in sub sample s additionally at six and eight years and mortality until 2005 . Setting Multicentre population based study in Engl and and Wales : two rural and three urban centres . Participants 438 participants who developed dementia from a population based study of 13 004 individuals aged 65 years and over drawn from primary care population registers . Main outcome measures Sociodemographic factors , cognitive function , specific health conditions , and self reported health collected at each interview . Cox ’s proportional hazards regression models were used to identify predictors of mortality from the selected variables in people who received diagnosis of dementia according the study ’s criteria . Results By December 2005 , 356 of the 438 ( 81 % ) participants who developed dementia during the study had died . Estimated median survival time from onset of dementia to death was 4.1 years ( interquartile range 2.5 - 7.6 ) for men and 4.6 years ( 2.9 - 7.0 ) for women . There was a difference of nearly seven years in survival between the younger old and the oldest people with dementia : 10.7 ( 25th centile 5.6 ) for ages 65 - 69 ; 5.4 ( interquartile range 3.4 - 8.3 ) for ages 70 - 79 ; 4.3 ( 2.8 - 7.0 ) for ages 80 - 89 , and 3.8 ( 2.3 - 5.2 ) years for ages ≥90 . Significant factors that predicted mortality in the presence of dementia during the follow-up included sex , age of onset , and disability . Conclusion These analyses give a population based estimated median survival for incident dementia of 4.5 years . Such estimates can be used for prognosis and planning for patients , carers , service providers , and policy makers Objectives : To provide up date d estimates of Alzheimer disease ( AD ) dementia prevalence in the United States from 2010 through 2050 . Methods : Probabilities of AD dementia incidence were calculated from a longitudinal , population -based study including substantial numbers of both black and white participants . Incidence probabilities for single year of age , race , and level of education were calculated using weighted logistic regression and AD dementia diagnosis from 2,577 detailed clinical evaluations of 1,913 people obtained from stratified r and om sample s of previously disease-free individuals in a population of 10,800 . These were combined with US mortality , education , and new US Census Bureau estimates of current and future population to estimate current and future numbers of people with AD dementia in the United States . Results : We estimated that in 2010 , there were 4.7 million individuals aged 65 years or older with AD dementia ( 95 % confidence interval [ CI ] = 4.0–5.5 ) . Of these , 0.7 million ( 95 % CI = 0.4–0.9 ) were between 65 and 74 years , 2.3 million were between 75 and 84 years ( 95 % CI = 1.7–2.9 ) , and 1.8 million were 85 years or older ( 95 % CI = 1.4–2.2 ) . The total number of people with AD dementia in 2050 is projected to be 13.8 million , with 7.0 million aged 85 years or older . Conclusion : The number of people in the United States with AD dementia will increase dramatically in the next 40 years unless preventive measures are developed The hypothesis is tested that the response to dextroamphetamine in terms of activity , attention , impulsivity , and autonomic activity is similar in normal ( N ) and hyperactive ( H ) children . Fourteen N and 15 H boys had skin conductance ( SC ) , heart rate ( HR ) , and finger temperature ( ST ) recorded during rest , presentation of eight 75- dB tones , and a reaction time ( RT ) procedure on three occasions : off drug ( Day 1 ) and after ingestion ( double-blind ) of placebo and of .5 mg/kg dextroamphetamine . Both N and H groups showed drug effects , compared to placebo , of reduced motor activity and impulsivity , improved attention ( RT ) , increased HR and HR slowing during RT foreperiods , and decreased ST . Both groups also had decreases in SC responsivity but in different parts of the test . Placebo compared to Day 1 produced increased activity and autonomic “ arousal ” but no change in RT . Stimulant drugs thus have similar behavioral and autonomic effects in both N and H boys , but the beneficial effects on behavior do not depend critically on increases in arousal Background / Aims : The presence of executive impairment in mild Alzheimer ’s disease ( AD ) has primarily been demonstrated by means of group comparison . Whether executive dysfunction is a common feature of mild AD or only present in a subgroup of patients remains unclear . The aim of this study was to describe the frequency of impairment on a set of internationally well-known executive tests in patients with very mild AD . Methods : Thirty-six patients with very mild AD ( MMSE scores above 23 ) and 32 healthy control subjects were administered a battery of 7 executive tests : Trail Making part B , Stroop Interference Test , modified Wisconsin Card Sorting Test ( WCST ) , category- and letter-based verbal fluency , a design fluency task and the Similarities subtest from WAIS . Impairment was defined as a score of 2 SD or more below control means . Results : Executive impairment on at least 1 measure was seen in 76 % of the patients , and 50 % were impaired on 2 or more tests . Trail Making B and Stroop Interference Test were impaired in more than 40 % , whereas only few patients were impaired on Similarities , WCST and design fluency . A wide variation of executive test profiles was seen among the patients . Conclusion : Executive impairments are common in early AD and not just a feature characteristic of a subgroup of patients . Complex attentional skills are more frequently affected than other executive functions . There is , however , considerable heterogeneity among AD patients in the pattern of executive dysfunction Patients who show the " strategy application disorder " can show deficits restricted to situations requiring multitasking , but the precise neuroanatomical and cognitive correlates of this problem have been rarely investigated . In this study , 60 people with circumscribed cerebral lesions and 60 age- and IQ-matched controls were given a multitasking procedure which allowed consideration of the relative contributions of task learning and remembering , planning , plan-following and remembering one 's actions to multitasking performance . Lesions to the left posterior cingulate and forceps major regions gave deficits on all measures except planning . Remembering task contingencies after a delay was also affected by lesions in the region of the left anterior cingulate , and rule-breaking and failures of task switching were additionally found in people with lesions affecting the medial and more polar aspects of Brodmann 's areas 8 , 9 and especially 10 . Planning deficits were associated with lesions to the right dorsolateral prefrontal cortex ( RDLPFC ) . A theory of the relationships between the cognitive constructs underpinning multitasking was tested using structural equation modelling . The results suggest that there are three primary constructs that support multitasking : retrospective memory , prospect i ve memory , and planning , with the second two drawing upon the products of the first . It is tentatively suggested that the left anterior and posterior cingulates together play some part in the retrospective memory dem and s , while the prospect i ve memory and planning components make dem and s on processes supported by the left areas 8 , 9 and 10 and the RDLPFC respectively OBJECTIVES The ability to resolve conflicts is indispensable to the function of daily life and decreases with cognitive decline . We hypothesized that subjects with different levels of cognitive impairment exhibit different conflict resolution performances and may be susceptible to interference effects at different stages . METHODS Sixteen normal controls ( NC ) , 15 mild cognitive impairment ( MCI ) and seven Alzheimer 's disease ( AD ) patients were recruited to perform in a modified Eriksen flanker task . RESULTS We observed that the AD and MCI patients exhibited smaller accuracy rate and longer response time compared to NC subjects . Longer N2 and P300 latencies were observed in the AD group . Furthermore , the MCI group showed a longer latency than the NC group in the P300 latency . The magnitude of the perceptual and response interference effects was larger in the AD group than the other groups , and the MCI group significantly differed from the NC group at the perceptual level . CONCLUSION The ability to resolve conflict decreased with impaired cognition and the perceptual and response interference effects may be useful in distinguishing MCI and AD . SIGNIFICANCE The perceptual or response interference effect may potentially be employed as a useful non-invasive probe for the clinical diagnosis of MCI and AD |
12,924 | 31,003,491 | Various study design s and participant characteristics moderated the temporal effects of acute exercise on episodic memory function .
For example , vigorous-intensity acute exercise , and acute exercise among young adults , had greater effects when the acute bout of exercise occurred before memory encoding or during the early memory consolidation period .
Conclusions : The timing of acute exercise plays an important role in the exercise-memory interaction .
Various exercise- and participant-related characteristics moderate this temporal relationship | BACKGROUND Accumulating research demonstrates that the timing of exercise plays an important role in influencing episodic memory .
However , we have a limited underst and ing as to the factors that moderate this temporal effect .
Thus , the purpose of this systematic review with meta- analysis was to evaluate the effects of study characteristics ( e.g. , exercise modality , intensity and duration of acute exercise ) and participant attributes ( e.g. , age , sex ) across each of the temporal periods of acute exercise on episodic memory ( i.e. , acute exercise occurring before memory encoding , and during memory encoding , early consolidation , and late consolidation ) . | Differences in the kinematics and pattern of relative regional cerebral blood flow ( rCBF ) during goal -directed arm aim ing were investigated with the use of a Fitts continuous aim ing paradigm with three difficulty conditions ( index of difficulty , ID ) and two aim ing types ( transport vs. targeting ) in six healthy right-h and ed young participants with the use of video-based movement trajectory analysis and positron emission tomography . Movement time and kinematic characteristics were analyzed together with the magnitude of cerebral blood flow to identify areas of brain activity proportionate to task and movement variables . Significant differences in rCBF between task conditions were determined by analysis of variance with planned comparisons of means with the use of group mean weighted linear contrasts . Data were first analyzed for the group . Then individual subject differences for the movement versus no movement and task difficulty comparisons were related to each individual subjects ' anatomy by magnetic resonance imaging . Significant differences in rCBF during reciprocal aim ing compared with no-movement conditions were found in a mosaic of well-known cortical and subcortical areas associated with the planning and execution of goal -directed movements . These included cortical areas in the left sensorimotor , dorsal premotor , and ventral premotor cortices , caudal supplementary motor area ( SMA ) proper , and parietal cortex , and subcortical areas in the left putamen , globus pallidus , red nucleus , thalamus , and anterior cerebellum . As aim ing task difficulty ( ID ) increased , rCBF increased in areas associated with the planning of more complex movements requiring greater visuomotor processing . These included bilateral occipital , left inferior parietal , and left dorsal cingulate cortices -- caudal SMA proper and right dorsal premotor area . These same areas showed significant increases or decreases , respectively , when contrast means were compared with the use of movement time or relative acceleration time , respectively , as the weighting factor . Analysis of individual subject differences revealed a correspondence between the spatial extent of rCBF changes as a function of task ID and the individuals ' movement times . As task ID decreased , significant increases in rCBF were evident in the right anterior cerebellum , left middle occipital gyrus , and right ventral premotor area . Functionally , these areas are associated with aim ing conditions in which the motor execution dem and s are high ( i.e. , coordination of rapid reversals ) and precise trajectory planning is minimal . These same areas showed significant increases or decreases , respectively , when contrast means were compared with the use of movement time or relative acceleration time , respectively , as the weighting factor . A functional dissociation result ed from the weighted linear contrasts between larger ( limb transport ) or smaller ( endpoint targeting ) type amplitude/target width aim ing conditions . Areas with significantly greater rCBF for targeting were the left motor cortex , left intraparietal sulcus , and left cau date . In contrast , those areas with greater rCBF associated with limb transport included bilateral occipital lingual gyri and the right anterior cerebellum . Various theoretical explanations for the speed/accuracy tradeoffs of rapid aim ing movements have been proposed since the original information theory hypothesis of Fitts . This is the first report to relate the predictable variations in motor control under changing task constraints with the functional anatomy of these rapid goal -directed aim ing movements . Differences in unimanual aim ing task difficulty lead to dissociable activation of cortical-subcortical networks . Further , these data suggest that when more precise targeting is required , independent of task difficulty , a cortical-subcortical loop composed of the contralateral motor cortex , intraparietal sulcus , and cau date is activated . This is consistent with the role of motor Purpose : To evaluate the temporal effects of acute exercise on episodic memory . Design : A quasi-experimental study . Sample : Eighty-eight college students ( N = 22 per group ) . Measures : Four experimental groups were evaluated , including a control group , exercising prior to memory encoding , exercising during encoding , and exercising during memory consolidation . The exercise stimulus consisted of a 15-minute moderate-intensity walk on a treadmill . Participants completed the Rey Auditory Verbal Learning Test ( RAVLT ) to assess learning and memory . Prospect i ve memory was assessed via a Red Pen Task . Long-term memory ( recognition and attribution ) of the RAVLT was assessed 20 minutes and 24 hours after exercise . Analysis : Repeated- measures analysis of variance ( ANOVA ) assessed the performance of RAVLT scores of trials 1 to 5 across groups . One-way ANOVA assessed the performance of individual trials across groups , whereas χ2 assessed the performance of the Red Pen Task across groups . Results : Regarding learning , the interaction of groups × trial was marginally statistically significant ( F 12,332 = 1.773 , P = .05 ) , indicating that the group which exercised before encoding did better than the group that exercised during encoding and consolidation . For both 24-hour recognition and attribution performance , the group that exercised before memory encoding performed significantly better than the group that exercised during consolidation ( P = .05 recognition , P = .006 attribution ) . Discussion : Engaging in a 15-minute bout of moderate-intensity walking before a learning task was effective in influencing long-term episodic memory The effects of acute aerobic exercise on cognitive functions in humans have been the subject of much investigation ; however , these studies are limited by several factors , including a lack of r and omized controlled design s , focus on only a single cognitive function , and testing during or shortly after exercise . Using a r and omized controlled design , the present study asked how a single bout of aerobic exercise affects a range of frontal- and medial temporal lobe-dependent cognitive functions and how long these effects last . We r and omly assigned 85 subjects to either a vigorous intensity acute aerobic exercise group or a video watching control group . All subjects completed a battery of cognitive tasks both before and 30 , 60 , 90 , or 120 min after the intervention . This battery included the Hopkins Verbal Learning Test-Revised , the Modified Benton Visual Retention Test , the Stroop Color and Word Test , the Symbol Digit Modalities Test , the Digit Span Test , the Trail Making Test , and the Controlled Oral Word Association Test . Based on these measures , composite scores were formed to independently assess prefrontal cortex- and hippocampal-dependent cognition . A three-way mixed Analysis of Variance was used to determine whether differences existed between groups in the change in cognitive function from pre- to post-intervention testing . Acute exercise improved prefrontal cortex- but not hippocampal-dependent functioning , with no differences found between delay groups . Vigorous acute aerobic exercise has beneficial effects on prefrontal cortex-dependent cognition and these effects can last for up to 2 hr after exercise HIGHLIGHTSAcute exercise following fear conditioning in animals leads to great fear learning . There is no evidence pertaining to the impact of acute exercise on intrusive emotional memories . Acute exercise following encoding of traumatic images led to greater intrusive memories . Findings reinforce animal models of exercise‐induced fear conditioning . ABSTRACT Brief physical exercise enhances memories for neutral events , and recently has been shown to modulate fear learning in animals . To date there is no evidence pertaining to the impact of exercise on emotional memories in humans . Accordingly , this study investigated the role of brief exercise in the development of emotional intrusive memories . Forty‐nine university students ( 18–29 year olds ) viewed a car accident film depicting accident and injury , and were then r and omly assigned to engage in either 10 min of intense exercise or easy walking . Two days following the experiment participants were assessed for both intrusive memories of the film and intentional recall of film details . Results indicated that participants in the exercise relative to the walking condition reported more intrusive memories , but not voluntarily recalled memories , of the car accident film two days later . These findings are consistent with recent evidence of exercise‐induced emotional learning in animals , and point to the potential for physical activity to contribute to the development of intrusions in the context of encoding emotionally‐laden information Persistent long-term memory depends on successful stabilization and integration of new memories after initial encoding [ 1 , 2 ] . This consolidation process is thought to require neuromodulatory factors such as dopamine , noradrenaline , and brain-derived neurotrophic factor [ 3 - 7 ] . Without the release of such factors around the time of encoding , memories will decay rapidly [ 3 , 5 , 6 , 8 ] . Recent studies have shown that physical exercise acutely stimulates the release of several consolidation-promoting factors in humans [ 9 - 14 ] , raising the question of whether physical exercise can be used to improve memory retention [ 15 - 17 ] . Here , we used a single session of physical exercise after learning to exogenously boost memory consolidation and thus long-term memory . Three groups of r and omly assigned participants first encoded a set of picture-location associations . Afterward , one group performed exercise immediately , one 4 hr later , and the third did not perform any exercise . Participants otherwise underwent exactly the same procedures to control for potential experimental confounds . Forty-eight hours later , participants returned for a cued-recall test in a magnetic resonance scanner . With this design , we could investigate the impact of acute exercise on memory consolidation and retrieval-related neural processing . We found that performing exercise 4 hr , but not immediately , after encoding improved the retention of picture-location associations compared to the no-exercise control group . Moreover , performing exercise after a delay was associated with increased hippocampal pattern similarity for correct responses during delayed retrieval . Our results suggest that appropriately timed physical exercise can improve long-term memory and highlight the potential of exercise as an intervention in educational and clinical setting Objective : To systematic ally summarize the experimental effects of exercise on cognitive-related memory function among young to middle-aged adults , which has yet to be done in the literature . Data Source : PubMed . Study Inclusion and Exclusion Criteria : Studies were included if they were published in the English language , indexed in PubMed , employed an experimental study design ( eg , traditional parallel group r and omized controlled trial : either acute intervention or chronic/training intervention study ) , and conducted among human adults . Studies were excluded if nonhumans ( ie , animal models ) were studied , if children/adolescents ( < 18 years ) or older adults ( > 50 years ) were evaluated , and if select chronic diseases ( eg , diabetes and dementia ) were present . Data Extraction : A systematic review approach was employed . Data Synthesis : An extraction table was created synthesizing the key results , and recommendations for future research are emphasized . Results : Among the 17 evaluated studies , 2 were published before the year 2000 ( ie , 1998 and 1999 ) , 2 were published in 2007 , and the remaining 13 were published in the years 2011 and beyond . This highlights the emergence of this research topic within this age-group ( young to middle-aged adults ) . Among the 17 evaluated studies , 14 were conducted among healthy sample s , with 3 conducted among those with a diagnosis of depression . Among the 17 studies , 4 employed a chronic training protocol , with 13 utilizing an acute exercise protocol . Among the 3 experimental studies in the depressed population , all demonstrated a favorable effect of exercise on memory function . Among the 14 trials in the nondepressed population , 10 ( 71 % ) demonstrated a favorable effect of exercise on some aspect of memory function . Conclusion : Acute and chronic exercise appears to play a pronounced effect on memory function among young to middle-aged adults . Implication s and recommendations for future research are outlined in this systematic review The broader purpose of this study was to examine the temporal effects of high-intensity exercise on learning , short-term and long-term retrospective memory and prospect i ve memory . Among a sample of 88 young adult participants , 22 were r and omized into one of four different groups : exercise before learning , control group , exercise during learning , and exercise after learning . The retrospective assessment s ( learning , short-term and long-term memory ) were assessed using the Rey Auditory Verbal Learning Test . Long-term memory including a 20-min and 24-hr follow-up assessment . Prospect i ve memory was assessed using a time-based procedure by having participants contact ( via phone ) the research ers at a follow-up time period . The exercise stimulus included a 15-min bout of progressive maximal exertion treadmill exercise . High-intensity exercise prior to memory encoding ( vs. exercise during memory encoding or consolidation ) was effective in enhancing long-term memory ( for both 20-min and 24-h follow-up assessment s ) . We did not observe a differential temporal effect of high-intensity exercise on short-term memory ( immediate post-memory encoding ) , learning or prospect i ve memory . The timing of high-intensity exercise may play an important role in facilitating long-term memory The hippocampus shrinks in late adulthood , leading to impaired memory and increased risk for dementia . Hippocampal and medial temporal lobe volumes are larger in higher-fit adults , and physical activity training increases hippocampal perfusion , but the extent to which aerobic exercise training can modify hippocampal volume in late adulthood remains unknown . Here we show , in a r and omized controlled trial with 120 older adults , that aerobic exercise training increases the size of the anterior hippocampus , leading to improvements in spatial memory . Exercise training increased hippocampal volume by 2 % , effectively reversing age-related loss in volume by 1 to 2 y. We also demonstrate that increased hippocampal volume is associated with greater serum levels of BDNF , a mediator of neurogenesis in the dentate gyrus . Hippocampal volume declined in the control group , but higher preintervention fitness partially attenuated the decline , suggesting that fitness protects against volume loss . Cau date nucleus and thalamus volumes were unaffected by the intervention . These theoretically important findings indicate that aerobic exercise training is effective at reversing hippocampal volume loss in late adulthood , which is accompanied by improved memory function Abstract Although anecdotal reports suggest that information processing and decision making is impaired immediately following prolonged periods of physical activity , results obtained from laboratory studies of exercise-induced fatigue have been inconsistent . Fatigue effects may be task specific and related to the time of post-exercise testing . The present study examined the effects on adults ' performance of two cognitive tasks that differed in processing dem and s over an 80-min period of fatigue . Thirty young adult men and women were r and omly assigned to either an exercise group and completed a 60-min bout of cycle ergometry at 90 % ventilatory threshold or a control group and rested for 60 min . Following interventions , each participant completed a simple and complex version of a visual perceptual discrimination test , a 40-min memory-based vigilance test and a repetition of the visual perceptual discrimination tests . Those who exercised evidence d significant decrements in performance on complex perceptual-discrimination tasks compared to participants who rested . The response time of exercisers during a memory-dem and ing vigilance test were significantly slower than those of participants who rested ; however , detection performance did not differ between groups neither was there a decrease in target detection across the vigil . The effects of exercise-induced fatigue may be task specific , with greater effects on perceptual tasks , which involve relatively automatic processing , compared to effortful memory-based tasks OBJECTIVE To simultaneously examine the effects of acute exercise intensity and free-living physical activity and sedentary behavior on cognitive function in young , healthy adults . PATIENTS AND METHODS Using a counterbalanced , crossover , r and omized controlled design , 87 young adults ( mean age , 21.4 years ) completed various cognitive assessment s with and without an acute bout of exercise preceding the assessment . Participants were r and omized into 1 of 4 groups to complete a 30-minute bout of acute exercise : control ( no exercise ) , light intensity ( 40%-50 % of predicted maximum heart rate [ HR(max ) ] ) , moderate intensity ( 51%-70 % of predicted HR(max ) ) , or vigorous intensity ( 71%-85 % of predicted HR(max ) ) . Subjectively and objective ly determined ( accelerometry ) physical activity and sedentary behavior were assessed to examine the association between these free-living behaviors and cognitive function . The study duration was August 26 , 2013 , to September 11 , 2014 . RESULTS Concentration-related cognition ( mean ± SD Feature Match test score ) was significantly higher after a 30-minute acute bout of moderate-intensity exercise ( 145.1±26.9 ) compared with cognitive assessment without exercise ( 121.3±19.2 ; P=.004 ) . Furthermore , question naire-determined sedentary behavior was inversely associated with visual attention and task switching ( Trail Making Test A score ) ( β=-0.23 ; P=.04 ) . Last , estimated cardiorespiratory fitness ( volume of maximum oxygen consumption ) was positively associated with reasoning-related cognitive function ( Odd One Out test score ) ( β=0.49 ; P=.05 ) ; when adding metabolic equivalent of task minutes per week to this model , the results were not significant ( β=0.47 ; P=.07 ) . CONCLUSION These findings provide some support for acute moderate-intensity exercise , sedentary behavior , and cardiorespiratory fitness being associated with executive functioning-related cognitive function in young , healthy adults We examined the effects of different acute exercise duration s and recovery periods on cognitive function in a counterbalanced , cross-over r and omized controlled experiment . We placed 352 participants , aged 18 to 35 years into one of 16 experimental groups . Each participant visited the laboratory twice , separated by a 1-week washout period . Either Visit 1 or 2 consisted of an acute bout of moderate-intensity treadmill exercise ( 10 , 20 , 30 , 45 , or 60 minutes ) followed by a period of rest ( 5 , 15 , or 30 minutes ) before taking a set of five cognitive tests ; the other visit consisted only of completing the cognitive tests ( no exercise ) . Cognitive tests sample d multiple cognitive parameters , including reasoning , concentration , memory , attention , and planning . We found that a short recovery period ( i.e. , 5 minutes ) may have a less favorable effect on planning ability but may be beneficial for memory . In addition , for various exercise duration s and recovery periods , a Group × Time × Resting ( nonexercise ) A cognitive interaction effect was observed such that for both memory and inhibitory cognitive ability , acute exercise ( vs. no exercise ) had an enhancement effect for those with lower resting cognitive functioning . The length of the acute exercise recovery period and resting cognitive ability most influenced the association between exercise and cognitive function In this study , we tested the effect of acute exercise on long-term memory , specifically the timing of exercise relative to the memory challenge . We assessed memory via paragraph recall , in which participants listened to two paragraphs ( exposure ) and recounted them following a 35-min delay . Participants ( n = 48 ) were r and omly assigned to one of three groups : exercise prior to exposure , exercise after exposure , or no-exercise . Exercise consisted of 30 min on a cycle ergometer , including 20 min at moderate intensity . Only the exercise-prior group recalled significantly more than the control group ( p < .05 ) . Differences among the exercise groups failed to reach significance ( p = .09 ) . Results indicated that acute exercise positively influenced recall and that exercise timing relative to memory task may have an impact on this effect Objective : In the present study , we examined the effect of working while seated , while st and ing , or while walking on measures of short-term memory , working memory , selective and sustained attention , and information-processing speed . Background : The advent of computer-based technology has revolutionized the adult workplace , such that average adult full-time employees spend the majority of their working day seated . Prolonged sitting is associated with increasing obesity and chronic health conditions in children and adults . One possible intervention to reduce the negative health impacts of the modern office environment involves modifying the workplace to increase incidental activity and exercise during the workday . Although modifications , such as sit-st and desks , have been shown to improve physiological function , there is mixed information regarding the impact of such office modification on individual cognitive performance and thereby the efficiency of the work environment . Method : In a fully counterbalanced r and omized control trial , we assessed the cognitive performance of 45 undergraduate students for up to a 1-hr period in each condition . Results : The results indicate that there is no significant change in the measures used to assess cognitive performance associated with working while seated , while st and ing , or while walking at low intensity . Conclusion : These results indicate that cognitive performance is not de grade d with short-term use of alternate workstations Two questions about the relationship between arousal and memory were investigated : First , does the source of arousal influence memory , and , second , what impact does arousal have on memory for detail ? In Experiment 1 , physiological arousal ( running or not running in place ) was factorially combined with emotional arousal ( viewing a neutral or an emotional slide sequence ) . Recognition memory was tested for gist , central detail , and background detail . Experiments 2 and 3 were similar to Experiment 1 , with the exception that a cued recall task was used in Experiment 2 and physiological arousal was manipulated with stationary biking in Experiment 3 . The results of these experiments indicated that physiological arousal had little impact on memory and that emotional arousal led to improvements in memory for both central and background detail . Overall , these results supported the notions that the source of arousal is an important determinant of an event ’s memorability ( Christianson , 1992a ) and that emotional arousal serves to enhance the scope of memory ( i.e. , flashbulb memory ; Brown & Kulik , 1977 ) Two experiments are reported that examine the possibility that exercise selectively influences different types of cognition . To our knowledge , these experiments represent the first attempt to study higher-cognitive processes during exercise . Theoretical thinking was guided by the transient hypofrontality hypothesis . In both experiments , athletes who exercised at a sustained , moderate pace were compared to sedentary controls on two neuropsychological tests , one that is generally regarded as heavily dependent on prefrontal cognition and one that is relatively insensitive to prefrontal operation . Results showed that during exercise performance on tests dem and ing prefrontal-dependent cognition was impaired , while at the same time , cognitive processes requiring little prefrontal activity were unaffected OBJECTIVE To study the acute effects of non-strenuous physical exercise on memory retrieval and visuo-motor performance in old-old nursing home residents . DESIGN A r and omized control trial . SETTING A nursing home . PARTICIPANTS Ambulatory volunteers from the nursing home , with all 20 shown to be normal on mental status . Three were male and 17 female , with a means of 84.5 years for age and 9.3 years for education . They were divided at r and om into an exercise and a control group . INTERVENTION A single 15-minute st and ardized bout of non-strenuous exercise administered independently to each participant in the exercise group . Control group participants watched a video of similar exercises for 15 minutes . MEASUREMENTS Two measures requiring the retrieval of category instances with semantic or initial consonant cues . Retrieval time was 60 seconds for each of four categories per measure . Visuo-motor performance was measured by Symbol Digit coding . Testing sessions were held before exercise , immediately post-exercise and 30 minutes post-exercise . RESULTS The group-by-time interaction was significant only for semantically cued memory ( P < 0.01 ) , with higher retrieval at post-testing only in the exercised group . The higher retrieval was mainly attributable to more new items retrieved by the exercise group at the immediate post-test ( P < 0.05 ) . CONCLUSIONS This study provides preliminary support for the hypothesis that non-strenuous physical exercise has positive acute effects on meaningfully cued memory Research demonstrates that acute exercise can enhance retrospective episodic memory performance . However , limited research has examined the effects of acute exercise on prospect i ve memory , and no studies have examined the effects of exercise on false memory performance . This study examined the potential effects of acute exercise on prospect i ve memory and false memory performance . A between-group r and omized controlled trial was employed , with participants ( college students ; Mage = 20 years ) r and omized into an exercise group ( 15-minute acute bout of treadmill walking ; N = 25 ) or a control group ( 15 minutes of sitting ; N = 26 ) . Prospect i ve memory was assessed from two laboratory and two naturalistic assessment s outside the lab . False memory was assessed using a word-list trial . There were no statistically significant differences in prospect i ve memory based on group allocation ( FGroup × Time = 1.17 ; P = 0.32 ; η2 = 0.06 ) . However , the control group recalled more false words and had a higher rate of false memory recognition ( FGroup × Time = 3.15 ; P = 0.01 ; η2 = 0.26 ) . These findings indicate that acute moderate-intensity aerobic exercise is not associated with prospect i ve memory performance but provides some suggestive evidence that acute exercise may reduce the rate of false memories The present experiment evaluated the effects of acute exercise on iconic memory and short- and long-term episodic memory . A two-arm , parallel-group r and omized experiment was employed ( n = 20 per group ; Mage = 21 year ) . The experimental group engaged in an acute bout of moderate-intensity treadmill exercise for 15 min , while the control group engaged in a seated , time-matched computer task . Afterwards , the participants engaged in a paragraph-level episodic memory task ( 20 min delay and 24 h delay recall ) as well as an iconic memory task , which involved 10 trials ( at various speeds from 100 ms to 800 ms ) of recalling letters from a 3 × 3 array matrix . For iconic memory , there was a significant main effect for time ( F = 42.9 , p < 0.001 , η2p = 0.53 ) and a trend towards a group × time interaction ( F = 2.90 , p = 0.09 , η2p = 0.07 ) , but no main effect for group ( F = 0.82 , p = 0.37 , η2p = 0.02 ) . The experimental group had higher episodic memory scores at both the baseline ( 19.22 vs. 17.20 ) and follow-up ( 18.15 vs. 15.77 ) , but these results were not statistically significant . These findings provide some suggestive evidence hinting towards an iconic memory and episodic benefit from acute exercise engagement Our previous work employing a between-subject r and omized controlled trial design suggests that exercising prior to memory encoding is more advantageous in enhancing retrospective episodic memory function when compared to exercise occurring during or after memory encoding . The present experiment evaluates this potential temporal effect of acute exercise on memory function while employing a within-subject , counterbalanced design . In a counterbalanced order ( via Latin squares ) , 24 participants completed four visits including ( 1 ) exercising ( moderate-intensity walking ) prior to memory encoding , ( 2 ) exercising during memory encoding , ( 3 ) exercising after memory encoding , and ( 4 ) a control visit ( no exercise ) . Retrospective memory function ( short term and long term ; 24-hour follow-up ) was assessed from a multitrial word list . Prospect i ve memory was assessed from a time-based task . Compared to all other visits , short-term memory was greater in the visit that involved exercising prior to memory encoding ( F = 3.76 ; P = .01 ; η2 = .79 ) . Similar results occurred for long-term memory , with no significant effects for prospect i ve memory performance . We provide robust evidence demonstrating that acute moderate-intensity exercise prior to memory encoding is optimal in enhancing short-term and long-term memory function when compared to no exercise as well as exercising during and after memory encoding Emerging work suggests that acute , moderate-intensity aerobic exercise may help to subserve episodic memory of neutral stimuli . Less investigated , however , is whether acute exercise is associated with enhanced memory recognition of emotional stimuli , which was the purpose of this experiment . A parallel-group r and omized controlled experiment was employed . Participants ( mean age = 20 yr ) were r and omized into an exercise ( n = 17 ) or control group ( n = 17 ) . The exercise group engaged in a 15-min bout of moderate-intensity treadmill walking . Emotional memory recognition was assessed via images from the International Affective Picture System , including assessment s of varying degrees of valence and arousal . Memory recognition was assessed at 1 day , 7 days , and 14 days post-memory encoding . We observed a significant main effect for time ( F(2 ) = 104.2 , p < 0.001 , η2p = 0.77 ) and a significant main effect for valence – arousal classification ( F(4 ) = 21.39 , p < 0.001 , η2p = 0.40 ) , but there was no significant time by group interaction ( F(2 ) = 1.09 , p = 0.34 , η2p = 0.03 ) , classification by group interaction ( F(4 ) = 0.12 , p = 0.97 , η2p = 0.01 ) , time by classification interaction ( F(8 ) = 1.78 , p = 0.08 , η2p = 0.05 ) , or time by classification by group interaction ( F(8 ) = 0.78 , p = 0.62 , η2p = 0.02 ) . In conclusion , emotional memory recognition decreased over the 14-day follow-up period and this rate of memory decay was not altered by acute moderate-intensity exercise engagement . We discuss these findings in the context of exercise intensity and the temporal effects of exercise Regular physical exercise improves cognitive functions and lowers the risk for age-related cognitive decline . Since little is known about the nature and the timing of the underlying mechanisms , we probed whether exercise also has immediate beneficial effects on cognition . Learning performance was assessed directly after high impact anaerobic sprints , low impact aerobic running , or a period of rest in 27 healthy subjects in a r and omized cross-over design . Dependent variables comprised learning speed as well as immediate ( 1 week ) and long-term ( > 8 months ) overall success in acquiring a novel vocabulary . Peripheral levels of brain-derived neurotrophic factor ( BDNF ) and catecholamines ( dopamine , epinephrine , norepinephrine ) were assessed prior to and after the interventions as well as after learning . We found that vocabulary learning was 20 percent faster after intense physical exercise as compared to the other two conditions . This condition also elicited the strongest increases in BDNF and catecholamine levels . More sustained BDNF levels during learning after intense exercise were related to better short-term learning success , whereas absolute dopamine and epinephrine levels were related to better intermediate ( dopamine ) and long-term ( epinephrine ) retentions of the novel vocabulary . Thus , BDNF and two of the catecholamines seem to be mediators by which physical exercise improves learning |
12,925 | 22,696,340 | The evidence from only one study indicates that increased water intake reduces the risk of recurrence of urinary stones and prolongs the average interval for recurrences .
Due to the lack of appropriate RCTs , no conclusions can be drawn on increased water intake for the primary and secondary prevention of urinary stones | BACKGROUND Urinary stones are a common condition characterised by high incidence and high recurrence rate .
For a long time , increased water intake has been the main preventive measure for the disease and its recurrence .
This is an up date of a review originally published in 2004 .
OBJECTIVES To assess the effectiveness of increased water intake for the primary and secondary prevention of urinary stones . | Patients with kidney stones are routinely advised to increase their fluid intake to decrease the risk of stone recurrence . However , there has been no detailed examination to determine whether the effect on recurrence varies by the type of beverage consumed . The authors conducted a prospect i ve study of the relation between the intake of 21 different beverages and the risk of symptomatic kidney stones in a cohort of 45,289 men , 40 - 75 years of age , who had no history of kidney stones . Beverage use and other dietary information was measured by means of a semiquantitative food frequency question naire in 1986 . During 6 years of follow-up ( 242,100 person-years ) , 753 incident cases of kidney stones were documented . After adjusting simultaneously for age , dietary intake of calcium , animal protein and potassium , thiazide use , geographic region , profession , and total fluid intake , consumption of specific beverages significantly added to the prediction of kidney stone risk ( p < 0.001 ) . After mutually adjusting for the intake of other beverages , the risk of stone formation decreased by the following amount for each 240-ml ( 8-oz ) serving consumed daily : caffeinated coffee , 10 % ( 95 % confidence interval 4 - 15 % ) ; decaffeinated coffee , 10 % ( 3 - 16 % ) ; tea , 14 % ( 5 - 22 % ) ; beer , 21 % ( 12 - 30 % ) ; and wine , 39 % ( 10 - 58 % ) . For each 240-ml serving consumed daily , the risk of stone formation increased by 35 % ( 4 - 75 % ) for apple juice and 37 % ( 1 - 85 % ) for grapefruit juice . The authors conclude that beverage type may have an effect on stone formation that involves more than additional fluid intake alone Pomegranate juice ( PJ ; also known as pomegreat pure juice ) provides a rich and varied source of polyphenolic compounds that may offer cardioprotective , anti-atherogenic and antihypertensive effects . The aim of this study was to investigate the effect of PJ consumption on glucocorticoids levels , blood pressure ( BP ) and insulin resistance in volunteers at high CVD risk . Subjects ( twelve males and sixteen females ) participated in a r and omised , placebo-controlled cross-over study ( BMI : 26·77 ( sd 3·36 ) kg/m2 ; mean age : 50·4 ( sd 6·1 ) years ) . Volunteers were assessed at baseline , and at weeks 2 and 4 for anthropometry , BP and pulse wave velocity . Cortisol and cortisone levels in urine and saliva were determined by specific ELISA methods , and the cortisol/cortisone ratio was calculated . Fasting blood sample s were obtained to assess plasma lipids , glucose , insulin and insulin resistance ( homeostasis model assessment of insulin resistance ) . Volunteers consumed 500 ml of PJ or 500 ml of a placebo drink containing a similar amount of energy . Cortisol urinary output was reduced but not significant . However , cortisol/cortisone ratios in urine ( P = 0·009 ) and saliva ( P = 0·024 ) were significantly decreased . Systolic BP decreased from 136·4 ( sd 6·3 ) to 128·9 ( sd 5·1 ) mmHg ( P = 0·034 ) , and diastolic BP from 80·3 ( sd 4·29 ) to 75·5 ( sd 5·17 ) mmHg ( P = 0·031 ) after 4 weeks of fruit juice consumption . Pulse wave velocity decreased from 7·5 ( sd 0·86 ) to 7·44 ( sd 0·94 ) m/s ( P = 0·035 ) . There was also a significant reduction in fasting plasma insulin from 9·36 ( sd 5·8 ) to 7·53 ( sd 4·12 ) mIU/l ( P = 0·025 ) and of homeostasis model assessment of insulin resistance ( from 2·216 ( sd 1·43 ) to 1·82 ( sd 1·12 ) , P = 0·028 ) . No significant changes were seen in the placebo arm of the study . These results suggest that PJ consumption can alleviate key cardiovascular risk factors in overweight and obese subjects that might be due to a reduction in both systolic and diastolic BP , possibly through the inhibition of 11β-hydroxysteroid dehydrogenase type 1 enzyme activity as evidence d by the reduction in the cortisol/cortisone ratio . The reduction in insulin resistance might have therapeutic benefits for patients with non-insulin-dependent diabetes , obesity and the metabolic syndrome OBJECTIVE The objective of the present study was to evaluate the effects of drinking 2 additional litres of water/day on several urinary risk factors for lithiasis in healthy subjects , through measurement of crystallization risk indices ( Tiselius CRI ) . MATERIAL S AND METHODS 48 healthy subjects , aged 25 to 50 were studied for urinary parameters including CRI in the laboratory ward , for 24 hours . After this first period , they were r and omized either to a 2L/d additional water intake ( treated group ) or usual fluid consumption ( control group ) for a 6 days period , which ended by a second measurement period in the laboratory ward for 24 hours . RESULTS Total additional water intake was actually 1.3L/d on average in treated subjects , because subjects decreased other usual sources of fluid intake . In 24 hour urine , Tiselius CRI varied differently among treated subjects and controls between the 2 periods ; male controls subjects experienced much higher values ( above 2 in average in first morning urine sample ) in the second period ( p = 0.05 ) . Of interest , in a transversal analysis , we observed a positive relation between BMI or waist circumference on the one h and , and with 24 hour urea excretion or osmotic load on the other h and . CONCLUSION These results show a beneficial effect of a final 1.3L additional water intake on Tiselius CRI in healthy subjects BACKGROUND A high dietary calcium intake is strongly suspected of increasing the risk of kidney stones . However , a high intake of calcium can reduce the urinary excretion of oxalate , which is thought to lower the risk . The concept that a higher dietary calcium intake increases the risk of kidney stones therefore requires examination . METHODS We conducted a prospect i ve study of the relation between dietary calcium intake and the risk of symptomatic kidney stones in a cohort of 45,619 men , 40 to 75 years of age , who had no history of kidney stones . Dietary calcium was measured by means of a semiquantitative food-frequency question naire in 1986 . During four years of follow-up , 505 cases of kidney stones were documented . RESULTS After adjustment for age , dietary calcium intake was inversely associated with the risk of kidney stones ; the relative risk of kidney stones for men in the highest as compared with the lowest quintile group for calcium intake was 0.56 ( 95 percent confidence interval , 0.43 to 0.73 ; P for trend , < 0.001 ) . This reduction in risk decreased only slightly ( relative risk , 0.66 ; 95 percent confidence interval , 0.49 to 0.90 ) after further adjustment for other potential risk factors , including alcohol consumption and dietary intake of animal protein , potassium , and fluid . Intake of animal protein was directly associated with the risk of stone formation ( relative risk for men with the highest intake as compared with those with the lowest , 1.33 ; 95 percent confidence interval , 1.00 to 1.77 ) ; potassium intake ( relative risk , 0.49 ; 95 percent confidence interval , 0.35 to 0.68 ) and fluid intake ( relative risk , 0.71 ; 95 percent confidence interval , 0.52 to 0.97 ) were inversely related to the risk of kidney stones . CONCLUSIONS A high dietary calcium intake decreases the risk of symptomatic kidney stones We evaluated the possible effects of a calcium entry blocking agent “ verapamil ” on new stone formation and /or regrowth of residual fragments after shock wave lithotripsy ( SWL ) during long-term follow-up ( > 30 months ) and compared the results with the success rates of adequate fluid intake . A total of 70 patients treated with SWL were r and omly divided into three different groups , in the first two of which the patients received different preventive measures with respect to stone recurrence and /or regrowth . While 25 patients received a calcium channel blocking agent , verapamil hydrochloride , beginning 3 days before SWL and continued 4 weeks after the procedure , an additional 25 patients were put in an enforced fluid intake program and the remaining 20 patients received no specific medication and /or measure apart from close follow-up . Patients were followed regularly with respect to the clearance/regrowth of the residual fragments and that of new stone formation during long-term follow-up ( within a mean follow-up of 30.4 months ) . The overall stone recurrence rate was 14 % ( 10/70 ) . Of the patients who became stone free ( 12/25 , 48 % ) in group I , only one patient ( 1/12 , 8.3 % ) showed a new stone formation during long-term follow-up . The figure was 40 % ( 4/10 ) in group II patients and 55 % ( 5/9 ) in group III patients receiving no specific medication . Regarding the residual stone fragments ( < 5 mm ) after SWL , again high fluid intake was found to be the most effective on stone regrowth rates ( 2/13 , 15.3 % ) . Patients treated with verapamil also had acceptable regrowth rates ( 3/15 , 20 % ) . Finally , verapamil treatment significantly improved the clearance of residual fragments ; while 7 out of 15 patients with residual fragments passed these particles successfully , ( 46.5 % ) in this group ; these figures were 46 % ( 6/13 ) and 18 % ( 2/13 ) in the remaining groups . Residual fragments located in lower calyces demonstrated a poor clearance rate with higher regrowth rates . Verapamil administration was found to be effective enough to limit the regrowth of residual fragments and also to facilitate residual fragment clearance after SWL . Patients receiving this medication seemed to pass the retained fragments easily in a shorter time than the others Diet plays an important role in the pathogenesis of kidney stones . Because the metabolism of many dietary factors , such as calcium , may change with age , the relation between diet and kidney stones may be different in older adults . Uncertainty also remains about the association between many dietary factors , such as vitamin C , magnesium , and animal protein , and the risk of kidney stone formation . To examine the association between dietary factors and the risk of incident , symptomatic kidney stones in men and to determine whether these associations vary with age , a prospect i ve cohort study was conducted of 45,619 men without a history of nephrolithiasis . Self-administered food frequency question naires were used to assess diet every 4 yr . A total of 1473 incident symptomatic kidney stones were documented during 477,700 person-years of follow-up . For men aged < 60 yr , the multivariate relative risk ( RR ) for stone formation in the highest quintile of dietary calcium as compared with the lowest quintile was 0.69 ( 95 % confidence interval [ CI ] , 0.56 to 0.87 ; P = 0.01 for trend ) . By contrast , there was no association between dietary calcium and stone formation in men aged 60 yr or older . The multivariate RR for men who consumed 1000 mg or greater of vitamin C per day compared with those who consumed less than the recommended dietary allowance of 90 mg/d was 1.41 ( 95 % CI , 1.11 to 1.80 ; P = 0.01 for trend ) . Other dietary factors showed the following multivariate RR among men in the highest quintile of intake compared with those in the lowest : magnesium , 0.71 ( 95 % CI , 0.56 to 0.89 ; P = 0.01 for trend ) ; potassium , 0.54 ( 95 % CI , 0.42 to 0.68 ; P < 0.001 for trend ) ; and fluid , 0.71 ( 95 % CI , 0.59 to 0.85 ; P < 0.001 for trend ) . Animal protein was associated with risk only in men with a body mass index < 25 kg/m(2 ) ( RR , 1.38 ; 95 % CI , 1.05 to 1.81 ; P = 0.03 for trend ) . Sodium , phosphorus , sucrose , phytate , vitamin B(6 ) , vitamin D , and supplemental calcium were not independently associated with risk . In conclusion , the association between calcium intake and kidney stone formation varies with age . Magnesium intake decreases and total vitamin C intake seems to increase the risk of symptomatic nephrolithiasis . Because age and body size affect the relation between diet and kidney stones , dietary recommendations for stone prevention should be tailored to the individual patient PURPOSE We define the role of urine volume as a stone risk factor in idiopathic calcium stone disease and test the actual preventive effectiveness of a high water intake . MATERIAL S AND METHODS We studied 101 controls and 199 patients from the first idiopathic calcium stone episode . After a baseline study period the stone formers were divided by r and omization into 2 groups ( 1 and 2 ) and they were followed prospect ively for 5 years . Followup in group 1 only involved a high intake of water without any dietetic change , while followup in group 2 did not involve any treatment . Each year clinical , laboratory and radiological evaluation was obtained to determine urinary stone risk profile ( including relative supersaturations of calcium oxalate , brushite and uric acid by Equil 2 ) , recurrence rate and mean time to relapse . RESULTS The original urine volume was lower in male and female stone formers compared to controls ( men with calcium oxalate stones 1,057 + /- 238 ml./24 hours versus normal men 1,401 + /- 562 ml./24 hours , p < 0.0001 and women calcium oxalate stones 990 + /- 230 ml./24 hours versus normal women 1,239 + /- 440 ml./24 hours , p < 0.001 ) . During followup recurrences were noted within 5 years in 12 of 99 group 1 patients and in 27 of 100 group 2 patients ( p = 0.008 ) . The average interval for recurrences was 38.7 + /- 13.2 months in group 1 and 25.1 + /- 16.4 months in group 2 ( p = 0.016 ) . The relative supersaturations for calcium oxalate , brushite and uric acid were much greater in baseline urine of the stone patients in both groups compared to controls . During followup , baseline values decreased sharply only in group 1 . Finally the baseline urine in patients with recurrences was characterized by a higher calcium excretion compared to urine of the patients without recurrences in both groups . CONCLUSIONS We conclude that urine volume is a real stone risk factor in nephrolithiasis and that a large intake of water is the initial therapy for prevention of stone recurrences . In cases of hypercalciuria it is suitable to prescribe adjuvant specific diets or drug therapy Investigations in healthy persons have shown that drinking mineral water containing HCO3 has a positive effect on urine supersaturated with calcium oxalate ( SSCaOx ) . The present study evaluates in a common setting whether these effects are also relevant in patients with multiepisodic urinary stone formation . A total of 34 patients with evident multiepisodic CaOx-urolithiasis were included in the study . Patients with hyperparathyroidism , renal tubular acidosis , Wilson ’s disease , Cushing disease , osteoporosis and malignant diseases were excluded . In a cross-over design and double-blinded the patients received 1.5 l of a mineral water with 2.673 mg HCO3/l ( test water ) or the same amount of water with a low mineral content ( 98 mg HCO3/l ) ( control water ) daily for 3 days . During the study period the patients diet was recorded in a protocol , but not st and ardised . The main target parameter was SSCaOx in 24 h urine . In addition , urinary pH and the most important inhibiting and promoting factors were measured in 24 h urine ( Ca , Ox , Mg , Cit ) . Both waters tested led to a highly significant increase in 24 h urine volume without a difference between each other . In the group , drinking the water containing HCO3 the urinary pH increased significantly and was within a range relevant for metaphylaxis of calcium oxalate stone formation ( x = 6.73 ) . This change was highly significant compared to the control group . In addition , significantly increased magnesium and citrate concentration were also observed . Supersaturation with calcium oxalate decreased significantly and to a relevant extent ; however , there was no difference between the waters tested . As expected , the risk of uric acid precipitation also decreased significantly under bicarbonate water intake . However , an increase of the risk of calcium phosphate stone formation was observed . It is evident that both waters tested are able to lower significantly and to a relevant extent the risk of urinary stone formation in patients with multiepisodic CaOx-urolithiasis . In addition , the bicarbonate water increases the inhibitory factors citrate and magnesium due to its content of HCO3 and Mg . Thus , it can be recommended for metaphylaxis of calcium oxalate and uric acid urinary stones BACKGROUND In older women and men , greater intakes of dietary calcium , potassium , and total fluid reduce the risk of kidney stone formation , while supplemental calcium , sodium , animal protein , and sucrose may increase the risk . Recently , phytate has been suggested to play a role in stone formation . To our knowledge , no prospect i ve information on the role of dietary factors and risk of kidney stone formation is available in younger women . METHODS We prospect ively examined , during an 8-year period , the association between dietary factors and the risk of incident symptomatic kidney stones among 96 245 female participants in the Nurses ' Health Study II ; the participants were aged 27 to 44 years and had no history of kidney stones . Self-administered food frequency question naires were used to assess diet in 1991 and 1995 . The main outcome measure was an incident symptomatic kidney stone . Cox proportional hazards regression models were used to adjust simultaneously for various risk factors . RESULTS We documented 1223 incident symptomatic kidney stones during 685 973 person-years of follow-up . After adjusting for relevant risk factors , a higher dietary calcium intake was associated with a reduced risk of kidney stones ( P = .007 for trend ) . The multivariate relative risk among women in the highest quintile of intake of dietary calcium compared with women in the lowest quintile was 0.73 ( 95 % confidence interval , 0.59 - 0.90 ) . Supplemental calcium intake was not associated with risk of stone formation . Phytate intake was associated with a reduced risk of stone formation . Compared with women in the lowest quintile of phytate intake , the relative risk for those in the highest quintile was 0.63 ( 95 % confidence interval , 0.51 - 0.78 ) . Other dietary factors showed the following relative risks ( 95 % confidence intervals ) among women in the highest quintile of intake compared with those in the lowest quintile : animal protein , 0.84 ( 0.68 - 1.04 ) ; fluid , 0.68 ( 0.56 - 0.83 ) ; and sucrose , 1.31 ( 1.07 - 1.60 ) . The intakes of sodium , potassium , and magnesium were not independently associated with risk after adjusting for other dietary factors . CONCLUSIONS A higher intake of dietary calcium decreases the risk of kidney stone formation in younger women , but supplemental calcium is not associated with risk . This study also suggests that some dietary risk factors may differ by age and sex . Finally , dietary phytate may be a new , important , and safe addition to our options for stone prevention Dietary factors are believed to play an important role in the formation of kidney stones [ 1 , 2 ] , but data on the influence of diet on stone formation in women are limited . The incidence of kidney stones in women is one third the incidence in men [ 3 ] ; the reason for this marked difference is unknown . Although differences in diet may contribute , the only available data on which comparisons between men and women can be based are from casecontrol studies that included few women . No studies have provided prospect i ve data on the relation between diet and kidney stones in women . In the past , a diet high in calcium was suspected of increasing the risk for calcium-containing kidney stones , particularly stones consisting of calcium oxalate ( the most common type ) . This finding has often led to restriction of calcium intake in patients who have had kidney stones in an attempt to decrease the likelihood of recurrence . In a large prospect i ve study in men , however , we recently found that high intake of dietary calcium was associated with a decreased risk for stone formation [ 2 ] . One possible explanation of this observation is that high calcium intake reduces oxalate absorption and subsequent urinary excretion of oxalate by binding oxalate in the gastrointestinal tract . Urinary oxalate may be more important than urinary calcium with respect to formation of calcium oxalate crystals [ 4 ] . Moreover , restriction of dietary calcium intake may result in negative calcium balance and decreased bone mineral density , particularly in patients with idiopathic hypercalciuria [ 5 ] . Supplemental calcium , such as calcium carbonate , is commonly used by adults in the United States . Large doses have been recommended for the prevention of various common disorders in women , such as osteoporosis and preeclampsia [ 6 , 7 ] . Although some research ers are concerned that high doses of supplemental calcium may increase the risk for kidney stone formation [ 7 ] , no data are available on this issue in women . Use of supplemental calcium increases urinary calcium excretion ; if not taken with meals , these supplements do not decrease urinary oxalate excretion . Thus , the overall effect of supplemental calcium may actually be an increased risk for stone formation . Clearly , information on the risk for stone formation associated with intake of supplemental calcium is essential to help patients decide whether to begin or continue to use calcium supplements . Other dietary factors may also be associated with the risk for kidney stone formation [ 1 , 2 ] . A diet high in sodium [ 8 ] , sucrose [ 9 ] , or animal protein [ 10 ] may increase the risk for stone formation , whereas a diet high in potassium [ 11 ] , magnesium [ 12 ] , or fluid may decrease this risk . To study the association between intake of dietary and supplemental calcium and other nutrients and the incidence of kidney stones in women , we conducted a 12-year prospect i ve analysis among 91 731 women who were participating in the Nurses ' Health Study and had no history of kidney stones at study entry . Methods Study Sample In 1976 , 121 700 female registered nurses who were 30 to 55 years of age and resided in 1 of 11 U.S. states completed and returned the initial question naire . These women constitute the Nurses ' Health Study cohort [ 13 ] . The cohort is followed by using biennial mailed question naires that ask about lifestyle practice s and other exposures of interest , as well as the incidence of newly diagnosed disease . The sample for our analysis was limited to the 91 731 women who answered the 1992 question naire , which included a question on lifetime history of kidney stones , and who had completed at least one of the four dietary question naires since 1980 ( the first year in which information on diet was collected ) . Assessment of Diet In 1980 , 1984 , 1986 , and 1990 , the participants were asked to complete semiquantitative food-frequency question naires , on which they reported the average intake of specified foods and beverages during the past year . The 1980 dietary question naire contained 61 items , and the subsequent question naires contained 131 items . Nutrient intake was computed from the reported frequency of consumption of each specified unit of food or beverage and from published data on the nutrient content of the specified portions [ 14 ] . Beginning in 1984 , information was also collected on the amount of supplemental calcium ( such as calcium carbonate ) ingested , either as separate supplements or as part of multivitamin preparations . The reproducibility and validity of the question naires completed by women in this cohort have been documented elsewhere [ 14 ] . A similar question naire has been shown to be valid and reproducible in men [ 15 ] . Nutrient values were adjusted for total energy intake by regressing total caloric intake on absolute nutrient intake [ 16 , 17 ] . Because total energy intake for a given person tends to be fixed within a narrow range , variations in nutrient intake are largely attributable to changes in composition of diet , not the total amount of food consumed . Energy-adjusted values reflect the nutrient composition of the diet independent of the total amount of food consumed . In addition , adjustment for energy reduces any variation introduced by question naire responses that underreported or overreported intake , thereby improving the accuracy of nutrient measurements [ 16 , 17 ] . To obtain additional information on the typical pattern of the use of supplemental calcium , we mailed a question naire to a r and om sample of 100 women who reported taking supplemental calcium on the 1994 biennial question naire . Eighty-six of these women responded . The question naire asked about the specific type of calcium salt ingested and whether the supplement was taken alone or with particular meals . Follow-up and Ascertainment of Cases The 1992 question naire asked whether the woman had ever received a diagnosis of a kidney stone and , if so , the date of the first occurrence . If the participant reported that a kidney stone had been diagnosed in 1980 ( when dietary information was first collected ) or later , we mailed her a supplementary question naire to confirm the diagnosis and to ascertain the date of occurrence ; the type of symptoms ; other relevant medical conditions ; and , if known , the type of stone . The rate of response to this supplementary question naire was 95 % . To confirm the validity of the participants ' reports , we obtained the medical records from a r and om sample of 90 of the women who reported a kidney stone . The records confirmed the diagnosis for all but 1 woman . We considered only cases of kidney stones that were diagnosed during the 12 years between the date on which the 1980 question naire was returned and 31 May 1992 . After we excluded women for whom the date of the kidney stone either could not be confirmed or fell outside of the study period , 91 731 women with no history of kidney stones remained in the study group . Statistical Analysis The study design was prospect i ve , and information on diet was collected before the onset of the kidney stone . For each participant , person-months of follow-up were counted from the date on which the 1980 question naire was returned 1 ) to the date on which a kidney stone developed or death occurred or 2 ) to 31 May 1992 , whichever occurred first . Information on exposures of interest that were recorded in responses to the 1980 question naire was up date d in 1984 , 1986 , and 1990 . We allocated person-months of follow-up according to exposure status at the start of each follow-up period ( indicated by the quintile of calcium intake and other variables ) . Dividing the cohort into quintiles of nutrient intake allowed us to examine a wide range of nutrient intake while maintaining enough participants in the highest and lowest categories . If complete information on diet was missing at the start of a time period , the participant was excluded for that time period . The relative risk-the incidence among women in a particular category of intake divided by the corresponding rate in the comparison category-was used as the measure of association [ 18 ] . Age-adjusted relative risks were calculated after the participants were stratified according to 5-year age categories [ 18 ] . The Mantel extension test was used to evaluate linear trends across categories of intake [ 19 ] . We used a proportional-hazards model to simultaneously adjust for several risk factors [ 20 ] . The variables considered in these models were selected on the basis of factors that published reports had indicated were related to formation of calcium stones . Variables included were age ( 5-year categories ) ; alcohol consumption ( eight categories ) ; body mass index ( five categories ) ; intake of vitamin B6 ( five categories ) ; intake of vitamin C ( five categories ) ; intake of supplemental calcium ( 0 mg/d , 1 to 100 mg/d , 101 to 500 mg/d , and 500 mg/d ) ; and dietary intake of calcium , animal protein , potassium , sodium , sucrose , magnesium , phosphorus , fiber , vitamin D , animal fat , total fat , and fluid ( quintile groups ) . We calculated 95 % CIs for all relative risks . All P values are two tailed . Results During the 903 849 person-years of follow-up , we documented 864 cases of new symptomatic kidney stones . Seventy-three women had systemic diseases potentially related to stone formation ( Table 1 ) . Although 13.4 % of the women reported having a urinary tract infection at the time the stone developed , only 3.9 % reported that they believed the stone formed as a result of this infection ( Table 1 ) . A family history of stone formation was reported by 24.2 % of the women with stones . Pain was the most frequent presenting symptom , occurring in 91.1 % of cases . Of the 390 women who reported information on the type of stone , 336 ( 86.2 % ) reported that the stone contained calcium . The incidence rate for the cohort was slightly less than 1 case per 1000 person-years ; the rate did not vary substantially by age ( Table 2 ) . Table 1 . Self-Reported Characteristics of the 864 Women with Incident OBJECTIVES This study was undertaken to identify a South African mineral water containing relatively high concentrations of calcium and magnesium and to investigate its effect on urinary biochemical and physicochemical risk factors associated with calcium oxalate kidney stone formation . DESIGN The study followed a change-over design in which each subject followed a r and omised sequence of three water-drinking protocol s involving their normal diet , a calcium and magnesium-rich mineral water and a mineral water deficient in these elements . SETTING University of Cape Town . SUBJECTS 54 volunteers without any previous history of stone disease ( 27 men , 27 women ) in the age group 21 - 35 years and 31 with a history of calcium oxalate kidney stones ( 24 men , 7 women ) in the age group 25 - 45 years participated in the study . OUTCOME MEASURES Both mineral waters favourably altered several risk factors . However , the effect of the calcium- and magnesium-rich water was shown to be significantly greater as it altered a larger number of these factors and induced several unique changes that were not achieved by the other water . CONCLUSIONS The risk of calcium oxalate stone formation can be significantly reduced by consumption of mineral water which is rich in calcium and magnesium An increase in fluid intake is routinely recommended for patients who have had a kidney stone to decrease the likelihood of recurrence . Higher fluid intake leads to increased urinary volume and , in turn , to a decreased concentration of lithogenic factors , presumably decreasing the rate of stone formation . Although it has not been proven successful , this approach is supported by many [ 1 - 4 ] but not all [ 5 ] authors . Of particular clinical interest are the risks and benefits conferred by different beverages . Beverages differ in the amount of potentially important constituents , such as caffeine , oxalate , and alcohol , that they contain . Therefore , they may influence stone formation differently . Several studies have examined the effects of particular beverages on changes in urine composition [ 6 , 7 ] , but few have examined the effect of particular beverages on kidney stone formation . In a retrospective study [ 8 ] , beer and coffee consumption were inversely associated with a history of kidney stones , and carbonated beverage ( soda ) consumption was positively associated with such a history . No significant associations were found with milk , tea , or water [ 8 ] . However , the authors did not adjust for other risk factors for kidney stone formation , such as dietary intake of calcium [ 9 ] . In a prospect i ve study of the intake of 21 different beverages and incident kidney stone formation in men [ 10 ] , we adjusted for nutrient intake and found an increased risk associated with consumption of apple juice and grapefruit juice and a decreased risk associated with consumption of coffee , tea , and alcoholic beverages . These results may not necessarily apply to women because the rate of kidney stone formation in women is one third that in men and the determinants of stone formation may differ by sex . No previous prospect i ve data are available on the relation between beverage use and risk for stone formation in women . We previously demonstrated an inverse association between total fluid intake and risk for incident stone formation in a large prospect i ve study of women [ 11 ] . To investigate whether the individual type of fluid ingested is important in women , we examined the relation between 17 different beverages and risk for symptomatic kidney stones in a cohort of 81 093 women in the United States . Methods Study Sample In 1976 , 121 700 female nurses 30 to 55 years of age completed and returned the initial question naire ; these women make up the Nurses ' Health Study cohort [ 12 ] . The cohort is followed through biennial mailed question naires that ask about lifestyle practice s , other exposures of interest , and the incidence of newly diagnosed disease . The sample for our current analysis was limited to the women who answered the 1992 question naire ( which included a question about lifetime history of kidney stones ) or the 1994 question naire ( which asked about kidney stones in the previous 2 years ) . In addition , it included only participants who had also answered either the 1986 or the 1990 dietary question naire , which elicited information on beverage use . Although information on some beverages was obtained on the 1980 and 1984 question naires , water had not been included . Because water is the most commonly used beverage , we used only the beverage information from the 1986 and 1990 question naires , which included water in the beverage list . We considered only cases of kidney stones that occurred during the 8 years between the return of the 1986 question naire and 31 May 1994 in women with no previous kidney stones . After further exclusion of women for whom the date of a kidney stone could not be confirmed , 81 093 women with no history of kidney stones at baseline remained for analysis . Assessment of Diet In 1986 and 1990 , participants were asked to complete semiquantitative food-frequency question naires on which they reported their average use of 131 specified foods and beverages during the previous year . Nutrient intake was computed from the reported frequency of consumption of each specified unit of food or beverage and from published data on the nutrient content of the specified portions [ 13 ] . In addition , information was collected on the amount of supplemental calcium ( such as calcium carbonate ) ingested , either alone or as part of multivitamin preparations . The reproducibility and validity of the question naires in this cohort were documented previously [ 13 - 15 ] . A similar question naire was shown to be valid and reproducible in men [ 16 , 17 ] . Individual beverage use was reported as the number of times that a st and ard serving size of a given beverage was consumed ; nine frequency categories were used , ranging from less than once per month to six or more times per day . Eighteen beverages were included on both the 1986 and the 1990 question naires . To calculate the average daily intake of each beverage , we multiplied the reported frequency of used by the serving size for the beverage . Because we had no a priori hypothesis that the various types of wine would differ for risk for stone formation , red and white wine were combined . A food-based validation study showed reasonable levels of reproducibility and validity for reported intake of the 11 individual beverages that were included in the 1980 version of the semiquantitative food-frequency question naire [ 14 ] . Pearson correlations between the food records and the question naire ranged from 0.36 for noncola carbonated beverages to 0.94 for beer , with a mean correlation for the beverages of 0.77 . We calculated total daily fluid intake by using data on frequency of use and serving size of individual beverages . In a validation study in men , a high correlation ( r = 0.59 ) between reported fluid intake and 24-hour urinary volume was reported [ 10 ] . We adjusted nutrient values for total energy intake by taking the residuals from a linear regression model with total caloric intake as the independent variable and nutrient intake as the dependent variable [ 18 , 19 ] . Energy-adjusted values reflect the nutrient composition of the diet independent of the total amount of food consumed . In addition , energy adjustment reduces any variation introduced by overall underreporting or overreporting of intake on the food-frequency question naire , thus improving the accuracy of nutrient measurements [ 18 , 19 ] . Calculation of beverage intake was not adjusted for total energy intake . Follow-up and Ascertainment of Cases On the 1992 question naire , we asked participants whether they had ever had a kidney stone diagnosed and the date of the first occurrence . The 1994 biennial question naire asked about a new diagnosis of a kidney stone since 1992 . If a kidney stone was reported , we mailed a supplementary question naire to the respondent to confirm the diagnosis and to ascertain the date of occurrence ; symptoms ; other relevant medical conditions ; and the type of stone , if known . The response rate to the supplementary question naire was 92 % . To confirm the validity of the responders ' reports , we obtained the medical records for a r and om sample of 90 of the women who reported having a kidney stone . The records confirmed the diagnosis in all but one case . Statistical Analysis In this prospect i ve study , information on diet was collected before any diagnosis of kidney stone was made . For each participant , person-months of follow-up were counted from the date of return of the 1986 question naire to the date of a diagnosis of kidney stone , death , or 31 May 1994 , whichever occurred first . Information on exposures of interest from the 1986 question naire was up date d in 1990 . We allocated person-months of follow-up according to exposure status ( the category of individual beverage use ) at the start of each follow-up period . If dietary information was missing at the start of a time period , the participant was excluded for that time period . For example , if a participant answered the 1986 question naire but not the 1990 question naire , she would contribute person-time only for the 1986 to 1989 period . If a participant answered the 1990 question naire but not the 1986 question naire , she would contribute person-time only for the 1990 to 1994 period . The proportion of participants with information missing for any individual beverage was 5 % or less for both the 1986 question naire ( Table 1 ) and the 1990 question naire ( data not shown ) . A validation study in men showed that missing items were not consumed in most instances ; thus , participants with information missing for an individual beverage were assigned to the lowest category of intake [ 17 ] . The categories for the beverage items were selected before the analyses on the basis of the frequency response for each individual item . The goal was to have enough participants in each category ( particularly the extreme categories ) to provide sufficient power to examine associations comparing extremes of intake . For each beverage , we assessed the nine individual response categories ( after examining the grouped categories ) to determine whether substantial variation was being masked . Because the results were very similar , the a priori selected grouped categories were used to provide more stable estimates . Table 1 . Distribution of Beverage Use among 65 584 Women with No History of Kidney Stones in 1986 * To formally test the null hypothesis that beverage type does not influence risk for kidney stones , we added intake of all specific beverages ( except water ) to a multiple logistic model that contained the total fluid intake variable and evaluated the change in total model deviance ( likelihood ratio test ) with 16 degrees of freedom . To make the results of the multivariate models more clinical ly useful and to have some st and ard for direct comparisons of different beverages , we converted the daily use of each beverage into the average number ( or fraction ) of 240-mL ( 8-oz ) servings consumed per day . This provided an estimate of the effect on risk for stone formation of increasing the consumption of an individual beverage by one unit ( Background : The purpose of this trial was to evaluate the efficacy of a low-animal-protein diet ( LAPD ) or a high-fiber diet ( HFD ) for the prevention of calcium nephrolithiasis recurrence . Methods : We conducted a 4-year r and omized trial comparing the effect of 2 diets in 175 idiopathic calcium stone formers . Fifty-five were assigned to a LAPD ( < 13 % of total energy derived from protein ) , 60 were assigned to a HFD ( > 25 g/day fiber ) and 60 were placed on a normal diet ( control group ) . The primary outcome measure was the time to the first recurrence of calcium nephrolithiasis . Daily urine compositions were analyzed at baseline , at month 4 ( M4 ) , M12 , M24 , M36 and M48 . Results : Seventy-three patients completed the trial ( 23 in the LAPD group , 27 in the HFD group and 23 in the control group ) . Recurrence was 48 % ( 11/23 ) in the LAPD group , 63 % ( 17/27 ) in the HFD group and 48 % ( 11/23 ) in the control group ( p = not significant ) . During follow-up , urinary calcium levels and other urine parameters did not change significantly in the 3 groups , except for a significant decrease in 24-hour urinary sulfate in the LAPD group . Conclusions : In idiopathic calcium stone formers , neither a LAPD nor a HFD appeared to provide protection against recurrence A multicentric study was carried out on 384 patients ( 231 males , mean age 28.3 years ; 153 females , mean age 40.8 years ) previously treated with extracorporeal shock wave lithotripsy for recurrent idiopathic calcium urolithiasis . Patients were selected and su bmi tted to different types of high fluid intake treatment ( oligomineral water with a calcium content of 15 mg/l vs. tap water with a calcium content ranging between 55 and 130 mg/l ) to evaluate stone recurrence and to identify any potential risk factors . During follow – up ( range 14–34 months , mean 19 months ) 44 ( 23 % ) of the 192 patients treated with tap water presented recurrence versus 32 ( 17 % ) of the 192 patients treated with Fiuggi mineral water , the difference in incidence between the two groups being 6 % . Of the possible predictors of recurrence , evaluated at the beginning of follow – up and analyzed in a multivariate statistical study , the 24–hour diuresis and calciuria were seen to be directly related to the recurrence |
12,926 | 29,355,906 | In the previous version of this Cochrane Review , published in 2012 , we found that antibiotics did reduce the risk of infection but did not reduce the number of dependent or deceased patients .
AUTHORS ' CONCLUSIONS Preventive antibiotics had no effect on functional outcome or mortality , but significantly reduced the risk of ' overall ' infections .
This reduction was driven mainly by prevention of urinary tract infection ; no effect for pneumonia was found | BACKGROUND Stroke is the main cause of disability in high-income countries and ranks second as a cause of death worldwide .
Infections occur frequently after stroke and may adversely affect outcome .
Preventive antibiotic therapy in the acute phase of stroke may reduce the incidence of infections and improve outcome .
OBJECTIVES To assess the effectiveness and safety of preventive antibiotic therapy in people with ischaemic or haemorrhagic stroke .
We wished to determine whether preventive antibiotic therapy in people with acute stroke:• reduces the risk of a poor functional outcome ( dependency and /or death ) at follow-up;• reduces the occurrence of infections in the acute phase of stroke;• reduces the occurrence of elevated body temperature ( temperature ≥ 38 ° C ) in the acute phase of stroke;• reduces length of hospital stay ; or• leads to an increased rate of serious adverse events , such as anaphylactic shock , skin rash , or colonisation with antibiotic-resistant micro-organisms . | Background and Purpose — Fever after stroke is a strong predictor for a negative outcome with infections as the most common cause . The aim of this pilot study was to evaluate the effects of prophylactic antibiotic therapy on the incidence and height of fever after acute ischemic stroke . Methods — This is a r and omized , controlled study of antibiotic prophylaxis in patients with ischemic stroke enrolled within 24 hours from clinical onset who presented bedridden ( modified Rankin score > 3 ) with no significant infection . Interventions included prophylactic mezlocillin plus sulbactam ( 3 × 2 g/1 g for 4 days ) or conventional management . Over 10 days , body temperature was continuously monitored , and the presence of infection was daily assessed . Primary end points were incidence and height of fever ; secondary end points included rate of infection and clinical outcome . Results — Sixty patients were included ( mean , 75 years ; median National Institutes of Health Stroke Scale score , 16 ) . Over the first 3 days , patients in the intervention group showed lower mean body temperatures as well as lower daily peak temperatures ( P<0.05 ) . Throughout the observation period , 15 of 30 patients in the intervention group but 27 of 30 patients in the conventionally treated group developed an infection ( P<0.05 ) . Mean interval until the diagnosis of infection was 5.1 days in the intervention group and 3.3 days in the control group ( P<0.05 ) . Clinical outcome was more favorable in patients with prophylactic therapy ( P=0.01 ) . Conclusions — In patients with acute severe stroke , prophylactic administration of mezlocillin plus sulbactam over 4 days decreases body temperature , lowers the rate of infection , and may be associated with a better clinical outcome BACKGROUND AND PURPOSE This prospect i ve , multicenter study was performed to determine the frequency of symptomatic complications up to 30 months after stroke using prespecified definitions of complications . METHODS We recruited 311 consecutive stroke patients admitted to hospital . Research nurses review ed their progress on a weekly basis until hospital discharge and again at 6 , 18 , and 30 months after stroke . RESULTS Complications during hospital admission were recorded in 265 ( 85 % ) of stroke patients . Specific complications were as follows : neurological-recurrent stroke ( 9 % of patients ) , epileptic seizure ( 3 % ) ; infections-urinary tract infection ( 24 % ) , chest infection ( 22 % ) , others ( 19 % ) ; mobility related-falls ( 25 % ) , falls with serious injury ( 5 % ) , pressure sores ( 21 % ) ; thromboembolism-deep venous thrombosis ( 2 % ) , pulmonary embolism ( 1 % ) ; pain-shoulder pain ( 9 % ) , other pain ( 34 % ) ; and psychological-depression ( 16 % ) , anxiety ( 14 % ) , emotionalism ( 12 % ) , and confusion ( 56 % ) . During follow-up , infections , falls , " blackouts , " pain , and symptoms of depression and anxiety remained common . Complications were observed across all 3 hospital sites , and their frequency was related to patient dependency and duration after stroke . CONCLUSIONS Our prospect i ve cohort study has confirmed that poststroke complications , particularly infections and falls , are common . However , we have also identified complications relating to pain and cognitive or affective symptoms that are potentially preventable and may previously have been underestimated Background and Purpose — Pneumonia has been estimated to occur in about one third of patients after acute stroke . Only limited data are available on stroke-associated pneumonia ( SAP ) in specialized neurological intensive care units ( NICUs ) . Methods — We enrolled 124 patients with acute stroke who were treated at our university hospital NICU in a prospect i ve observational study . Incidence rates and risk factors of SAP and long-term clinical outcome were determined . Results — SAP incidence was 21 % with a spectrum of pathogens , which is comparable to previously published data on general ICU patients . Mechanical ventilation , multiple location , and vertebrobasilar stroke , as well as dysphagia and abnormal chest x-ray findings , were identified as risk factors for the disease . SAP patients showed higher mortality rates than nondiseased subjects ( acute , 26.9 % versus 8.2 % ; long-term , 35.3 % versus 14.3 % ) and a significantly poorer long-term clinical outcome ( Barthel Index , 50.5±42.4 versus 81.5±27.8 ; Rankin Scale , 3.5±1.7 versus 2.2±1.6 ) . Conclusions — Our data underline the considerable epidemiological and prognostic impact of SAP for the treatment of acute stroke patients in a specialized NICU setting . They demonstrate that the occurrence of SAP deteriorates clinical outcome in these patients . Our results allow us to identify high-risk stroke patients at time of NICU admission in whom the use of preventive treatment strategies is most promising BACKGROUND Urinary tract infection ( UTI ) is a recognized complication of stroke . We aim ed to determine the incidence of UTI after acute stroke , the risk factors associated with this complication , and its association with outcome . METHODS Prospect i ve study of consecutive acute stroke patients admitted to an urban teaching hospital . Routine clinical assessment included the modified National Institutes of Health Stroke Scale ( mNIHSS ) and modified Rankin scale ( mRS ) . Patients were followed up for 3 months , including recording of clinician diagnosis of UTI . RESULTS We studied 412 patients ; 65 ( 15.8 % ) were diagnosed with UTI , at a median of 14 days ( IQR = 4 - 39 ) post-stroke . In a binomial multivariate regression analysis , UTI was associated with urinary catheterization ( OR = 3.03 , 95 % CI 1.41 - 6.52 ) , higher mRS ( OR = 1.85 , 1.29 - 2.64 ) and increasing age ( OR = 1.51 , 1.13 - 2.00 for each decade ) . UTI was associated with death or disability at 3 months , however , this link was attenuated and became non-significant when measures of stroke severity and pre-stroke morbidity were included in a multivariate analysis . CONCLUSION UTI is common after acute stroke . It is associated with urinary catheterization , post-stroke disability and increasing age . Avoidance of catheterization might reduce the incidence of this common complication Objectives To provide information on the frequency and reasons for outcome reporting bias in clinical trials . Design Trial protocol s were compared with subsequent publication(s ) to identify any discrepancies in the outcomes reported , and telephone interviews were conducted with the respective trialists to investigate more extensively the reporting of the research and the issue of unreported outcomes . Participants Chief investigators , or lead or co authors of trials , were identified from two sources : trials published since 2002 covered in Cochrane systematic review s where at least one trial analysed was suspected of being at risk of outcome reporting bias ( issue 4 , 2006 ; issue 1 , 2007 , and issue 2 , 2007 of the Cochrane library ) ; and a r and om sample of trial reports indexed on PubMed between August 2007 and July 2008 . Setting Australia , Canada , Germany , the Netherl and s , New Zeal and , the United Kingdom , and the United States . Main outcome measures Frequency of incomplete outcome reporting — signified by outcomes that were specified in a trial ’s protocol but not fully reported in subsequent publications— and trialists ’ reasons for incomplete reporting of outcomes . Results 268 trials were identified for inclusion ( 183 from the cohort of Cochrane systematic review s and 85 from PubMed ) . Initially , 161 respective investigators responded to our requests for interview , 130 ( 81 % ) of whom agreed to be interviewed . However , failure to achieve subsequent contact , obtain a copy of the study protocol , or both meant that final interviews were conducted with 59 ( 37 % ) of the 161 trialists . Sixteen trial investigators failed to report analysed outcomes at the time of the primary publication , 17 trialists collected outcome data that were subsequently not analysed , and five trialists did not measure a prespecified outcome over the course of the trial . In almost all trials in which prespecified outcomes had been analysed but not reported ( 15/16 , 94 % ) , this under-reporting result ed in bias . In nearly a quarter of trials in which prespecified outcomes had been measured but not analysed ( 4/17 , 24 % ) , the “ direction ” of the main findings influenced the investigators ’ decision not to analyse the remaining data collected . In 14 ( 67 % ) of the 21 r and omly selected PubMed trials , there was at least one unreported efficacy or harm outcome . More than a quarter ( 6/21 , 29 % ) of these trials were found to have displayed outcome reporting bias . Conclusion The prevalence of incomplete outcome reporting is high . Trialists seemed generally unaware of the implication s for the evidence base of not reporting all outcomes and protocol changes . A general lack of consensus regarding the choice of outcomes in particular clinical setting s was evident and affects trial design , conduct , analysis , and reporting Background : We have recently shown that ischemic stroke causes a stress-mediator-induced long-lasting immunodepressive state in mice . Methods : Using head magnetic resonance imaging and st and ardized immunoassays , we prospect ively investigated whether poststroke immunodepression is also seen in humans . Results : Compared to healthy volunteers ( n = 30 ) , a rapid depression of lymphocyte counts and a functional deactivation of monocytes and T helper type 1 cells was observed in acute stroke patients ( SP ; n = 40 ) . Immunodepression was more pronounced in patients with severe clinical deficit or large infa rct ion . On admission the combination of monocytic tumor necrosis factor α release ex vivo and the National Institute of Health Stroke Scale score were the best predictors for nosocomial infection , preferentially affecting older SP . Conclusion : Our data provide evidence for an immediate suppression of cell-mediated immune responses after ischemic stroke in humans Objective To determine the incidence rates of hospital acquired infections ( HAI ) during the first 14 days after ICU discharge after treatment during ICU-stay with Selective Decontamination of the Digestive tract ( SDD ) , Selective Oropharyngeal Decontamination ( SOD ) or St and ard Care ( SC ) . Design Prospect i ve observational study . Setting ICUs in two tertiary care hospitals . Patients Patients discharged from the ICU to the ward . Interventions None . Measurements and results Post-ICU incidences of HAI per 1,000 days at risk were 11.2 , 12.9 and 8.3 for patients that had received SDD ( n = 296 ) , SOD ( n = 286 ) or SC ( n = 289 ) respectively in ICU , yielding relative risks , as compared to SC , of 1.49 ( CI95 0.9–2.47 ) for SOD and 1.44 ( CI95 0.87–2.39 ) for SDD . Incidences of surgical site infections ( per 100 surgical procedures ) were 4 after SC and 11.8 and 8 after SOD and SDD ( p = 0.04 ) . Among patients that succumbed in the hospital after ICU-stay ( n = 58 ) eight ( 14 % ) had developed HAI after ICU discharge ; 3 of 21 after SDD , 3 of 15 after SOD and 2 of 22 after SC . Conclusions Incidences of HAI in general wards tended to be higher in patients that had received either SDD or SOD during ICU-stay , but it seems unlikely that these infections have an effect on hospital mortality rates Background Pneumonia is a major risk factor of death after acute stroke . In a mouse model , preventive antibacterial therapy with moxifloxacin not only prevents the development of post-stroke infections , it also reduces mortality , and improves neurological outcome significantly . In this study we investigate whether this approach is effective in stroke patients . Methods Preventive ANtibacterial THERapy in acute Ischemic Stroke ( PANTHERIS ) is a r and omized , double-blind , placebo-controlled trial in 80 patients with severe , non-lacunar , ischemic stroke ( NIHSS>11 ) in the middle cerebral artery ( MCA ) territory . Patients received either intravenous moxifloxacin ( 400 mg daily ) or placebo for 5 days starting within 36 hours after stroke onset . Primary endpoint was infection within 11 days . Secondary endpoints included neurological outcome , survival , development of stroke-induced immunodepression , and induction of bacterial resistance . Findings On intention-to treat analysis ( 79 patients ) , the infection rate at day 11 in the moxifloxacin treated group was 15.4 % compared to 32.5 % in the placebo treated group ( p = 0.114 ) . On per protocol analysis ( n = 66 ) , moxifloxacin significantly reduced infection rate from 41.9 % to 17.1 % ( p = 0.032 ) . Stroke associated infections were associated with a lower survival rate . In this study , neurological outcome and survival were not significantly influenced by treatment with moxifloxacin . Frequency of fluoroquinolone resistance in both treatment groups did not differ . On logistic regression analysis , treatment arm as well as the interaction between treatment arm and monocytic HLA-DR expression ( a marker for immunodepression ) at day 1 after stroke onset was independently and highly predictive for post-stroke infections . Interpretation PANTHERIS suggests that preventive administration of moxifloxacin is superior in reducing infections after severe non-lacunar ischemic stroke compared to placebo . In addition , the results emphasize the pivotal role of immunodepression in developing post-stroke infections . Trial Registration Controlled-Trials.com IS RCT The third most common stroke complication is infection . We studied the rates of aspiration pneumonia and urinary tract infection ( UTI ) , their risk factors and their effect on outcome in the 1455 Glycine Antagonist ( Gavestinel ) in Neuroprotection ( GAIN ) International patients with ischaemic stroke . Forward stepwise logistic regression and Cox proportional hazards modelling identified baseline factors that predicted events and the independent effect of events up to day 7 on poor stroke outcome at 3 months in patients alive at day 7 , after correcting for prognostic factors . Higher baseline National Institute of Health Stroke Scale ( NIHSS ) and age , male gender , history of diabetes and stroke subtype predicted pneumonia , which occurred in 13.6 % of patients . Female gender and higher baseline NIHSS and age predicted UTI , which occurred in 17.2 % of patients . Pneumonia was associated with poor outcome by mortality ( hazard ratio , 2.2 ; 95 % confidence interval , 1.5 - 3.3 ) , Barthel index ( < 60 ) ( odds ratio , 3.8 ; 2.2 - 6.7 ) , NIHSS ( 4.9 ; 1.7 - 14 ) and Rankin scale ( > /=2 ) ( 3.4 ; 1.4 - 8.3 ) . UTI was associated with Barthel index ( 1.9 ; 1.2 - 2.9 ) , NIHSS ( 2.2 ; 1.2 - 4.0 ) and Rankin scale ( 3.1 ; 1.6 - 4.9 ) . Pneumonia and UTI are independently associated with stroke poor outcome . Patients with identified risk factors must be closely monitored for infection BACKGROUND AND PURPOSE It is unsettled whether stroke-associated infection ( SAI ) is an independent prognostic factor , and a recent clinical trial failed to show that antibiotic prophylaxis prevented SAI . Contrarily , this trial suggested that antibiotic prophylaxis impaired clinical recovery . We sought to evaluate the predisposing factors and clinical consequences of SAI to gather additional insight on the need of exploring other antibiotics in acute stroke . METHODS Between March 2001 and April 2002 , 229 consecutive patients were admitted into the neurological wards within 24 hours of stroke onset . Demographics , risk factors , National Institutes of Health Stroke Scale ( NIHSS ) score , vital data , imaging , and laboratory findings were prospect ively evaluated . SAI was treated as early as possible . Multivariate regression analyses assessed predisposing factors of SAI and the independent association between SAI and poor stroke outcome at day 7 ( Rankin > 2 ) . RESULTS Sixty ( 26 % ) patients developed SAI , most frequently chest infections , and within 3 days of stroke onset . Tube feeding ( odds ratio [ OR ] , 3.2 ; 95 % CI , 1.3 , 7.8 ) was the strongest predisposing factor of SAI . Poor outcome at hospital discharge was associated to baseline NIHSS score ( OR , 10.0 ; 95 % CI , 1.5 , 100 ) and tube feeding ( OR , 16.6 ; 95 % CI , 2.9 , 100.0 ) , adjusted for confounders including antibiotic use . SAI was not independently associated to poor outcome ( OR , 0.9 ; 95 % CI , 0.9 , 1.0 ) . CONCLUSIONS SAI is a marker of the severity of stroke without an independent outcome effect when it is promptly treated . These results support current stroke guidelines that advise prompt treatment of infection and warn against antibiotic prophylaxis . Yet , these recommendations should not prevent the performance of acute stroke trials assessing the value of antibiotics with acknowledged neuroprotective properties Background and Purpose — Early infection after stroke is frequent but the clinical value of antibiotic prophylaxis in acute stroke has never been explored . Objective and Methods — The Early Systemic Prophylaxis of Infection After Stroke ( ESPIAS ) is a r and omized , double-blind , placebo-controlled study of antibiotic prophylaxis in patients older than 18 years with nonseptic ischemic or hemorrhagic stroke enrolled within 24 hours from clinical onset . Interventions included intravenous levofloxacin ( 500 mg/100 mL/d , for 3 days ) or placebo ( 0.9 % physiological serum ) in addition to optimal care . A sample size of 240 patients was calculated to identify a 15 % absolute risk reduction of the primary outcome measure , which was the incidence of infection at day 7 after stroke . Secondary outcome measures were neurological outcome and mortality at day 90 . Results — Based on a preplanned futility analysis , the study was interrupted prematurely when 136 patients had been included . Levofloxacin and placebo patients had a cumulative rate of infection of 6 % and 6 % ( P=0.96 ) at day 1 ; 10 % and 12 % ( P=0.83 ) at day 2 ; 12 % and 15 % ( P=0.66 ) at day 3 ; 16 % and 19 % ( P=0.82 ) at day 7 ; and 30 % and 33 % ( P=0.70 ) , at day 90 . Using logistic regression , favorable outcome at day 90 was inversely associated with baseline National Institutes of Health Stroke Scale ( OR , 0.72 ; 95 % CI , 0.59 to 0.89 ; P=0.002 ) and allocation to levofloxacin ( OR , 0.19 ; 95 % CI , 0.04 to 0.87 ; P=0.03 ) . Conclusions — Prophylactic administration of levofloxacin ( 500 mg/100 mL/day for 3 days ) is not better than optimal care for the prevention of infections in patients with acute stroke Objective To evaluate if a 3-day ampicillin-sulbactam prophylaxis can reduce the occurrence of early-onset pneumonia ( EOP ) in comatose mechanically-ventilated patients . Design This was a single-centre , prospect i ve , r and omised , open study . Setting A 10-bed general-neurological ICU in a 2,000-bed university hospital . Patients and participants Comatose mechanically-ventilated patients with traumatic , surgical or medical brain injury . Interventions Patients were r and omized to either ampicillin-sulbactam prophylaxis ( 3 g every 6 h for 3 days ) plus st and ard treatment or st and ard treatment alone . Measurements and results Main outcome was the occurrence of EOP . Secondary outcome measures were occurrence of late-onset pneumonia , percentage of non-pulmonary infections and of emerging multiresistant bacteria , duration of mechanical ventilation and of ICU stay and ICU mortality . Interim analysis at 1 year demonstrated a statistically significant reduction of EOP in the ampicillin-sulbactam group , and the study was interrupted . Overall , 39.5 % of the patients developed EOP , 57.9 % in the st and ard treatment group and 21.0 % in the ampicillin-sulbactam group ( chi-square 5.3971 ; P = 0.022 ) . Relative risk reduction of EOP in patients receiving ampicillin-sulbactam prophylaxis was 64 % ; the number of patients to be treated to avoid one episode of EOP was three . No differences in other outcome parameters were found ; however , the small sample size precluded a definite analysis . Conclusions Antibiotic prophylaxis with ampicillin-sulbactam significantly reduced the occurrence of EOP in critically ill comatose mechanically ventilated patients . This result should encourage a large multicenter trial to demonstrate whether ampicillin-sulbactam prophylaxis reduces patient mortality , and whether antibiotic resistance is increased in patients receiving prophylaxis One hundred and twenty three elderly patients without urinary tract infection who required an indwelling urinary catheter because of cerebrovascular disease were divided into three groups . One was given methenamine hippurate ( MH ) , one nitrofurantoin ( NF ) , while a control group received no prophylactic urinary tract disinfectant . Catheter complications , symptomatic urinary tract infections and the clinical course were recorded . At regular intervals bacteria were cultured from the urine , tests were made for antibody-coated bacteria ( ACB ) and routine laboratory investigations were performed . NF significantly delayed the appearance of ACB ; however , it did not prevent their appearance if a catheter was used for more than two months , by which time ACB were present in most patients irrespective of treatment . MH had less effect on the bacteriological findings , although it significantly decreased the need for antibiotic courses given for treatment of symptomatic urinary tract infections . In both MH- and NF-groups there were fewer patients with mechanical catheter complications . Forty seven patients died , generally due to cerebrovascular disease , and 22 autopsies were performed . Gross inflammatory changes in the urinary tract were commonly found at autopsy in all groups if a catheter had been used for more than two weeks . A positive test for ACB considerably increased the probability of inflammatory changes in the kidneys , but because of the frequency of such changes after prolonged use of an indwelling catheter , the test does not seem to offer much advantage as a guideline for therapy . Prophylactic urinary tract disinfectants may not be warranted in all patients with an indwelling catheter . If , however , recurrent clinical complications such as clogging of the catheter or symptomatic infection occur , continuous use of a urinary tract disinfectant is indicated . MH is preferred because it has fewer side effects than NF Few studies have investigated the risk factors for nosocomial infections developed in neurology intensive care units ( ICUs ) . In this study , the risk factors for ICU-acquired infections in patients with cerebral hemorrhage and cerebral infa rct who were treated for more than 24 h at the Ankara Training and Research Hospital were prospect ively evaluated over a study period of 14 months . Of 171 patients included in the study , 71 ( 41.5 % ) were found to have acquired 163 infections in the ICU unit throughout 1,867 patient days . The rate of infection per 100 patients admitted was 95.3 , and per 1,000 patient days , 87.3 . The most common nosocomial infections were urinary tract infection ( 42.9 % ) , pneumonia ( 27 % ) and primary bacteremia ( 19 % ) . Multivariate logistic regression analysis revealed age > or = 70 ( P < 0.05 ) , the presence of a central venous catheter ( P=0.004 ) , and parenteral nutrition ( P=0.02 ) as ICU-acquired infection risk factors . The presence of infection on admission was identified as a factor decreasing the risk of ICU-acquired infection ( P < 0.001 ) . The high infection rates found in this study may be due to lack of full compliance to infection control measures . In conclusion , each type of ICU has its own epidemiological findings for nosocomial infections and thus needs to determine the risk factors using periodical surveillance studies to guide control measures BACKGROUND Swallowing dysfunction after stroke is common , but there is little reliable evidence for how the disorder should be managed . This study compared st and ard low-intensity and high-intensity behavioural interventions with usual care for dysphagia . METHODS 306 patients with clinical dysphagia admitted to hospital with acute stroke were r and omly assigned to receive usual care ( n=102 ) , prescribed by the attending physician ; st and ard low-intensity intervention ( n=102 ) , comprising swallowing compensation strategies and diet prescription three times weekly for up to a month ; or st and ard high-intensity intervention and dietary prescription ( n=102 ) , at least daily for up to a month . The primary outcome measure was survival free of an abnormal diet at 6 months . Analysis was done by intention to treat . This study is registered with Clinical Trials.gov , number NCT00257764 . FINDINGS 60 patients died and three patients were lost to follow up before the 6-month analysis . Of patients r and omly allocated usual care , 56 % ( 57/102 ) survived at 6 months free of an abnormal diet compared with 67 % ( 136/204 ) allocated st and ard swallowing therapy ( relative risk 1.19 , 95 % CI 0.98 - 1.45 ) . St and ard swallowing therapy was associated with a non-significant trend toward a reduction in death ( 0.80 , 0.5 - 1.3 ) , institutionalisation ( 0.69 , 0.4 - 1.1 ) , and dependency ( 1.05 , 0.8 - 1.3 ) ; a significant reduction in swallowing-related medical complications ( 0.73 , 0.6 - 0.9 ) , chest infection ( 0.56 , 0.4 - 0.8 ) , and death or institutionalisation ( 0.73 , 0.55 - 0.97 ) ; and a significant rise in the proportion of patients regaining swallowing function ( 1.41 , 1.03 - 1.94 ) by 6 months . Compared with usual care and low-intensity therapy , high-intensity therapy was associated with an increased proportion of patients who returned to a normal diet ( p=0.04 ) and recovered swallowing ( p=0.02 ) by 6 months . INTERPRETATION These data show a consistent trend towards more favourable outcomes in dysphagic stroke patients who are assigned a st and ard programme of early behavioural swallowing intervention , including active therapeutic approaches and dietary modification Background : Ischemic animal model studies have shown a neuroprotective effect of minocycline . Objective : To analyze the effect of minocycline treatment in human acute ischemic stroke . Methods : We performed an open-label , evaluator-blinded study . Minocycline at a dosage of 200 mg was administered orally for 5 days . The therapeutic window of time was 6 to 24 hours after onset of stroke . Data from NIH Stroke Scale ( NIHSS ) , modified Rankin Scale ( mRS ) , and Barthel Index ( BI ) were evaluated . The primary objective was to compare changes from baseline to day 90 in NIHSS in the minocycline group vs placebo . Results : One hundred fifty-two patients were included in the study . Seventy-four patients received minocycline treatment , and 77 received placebo . NIHSS and mRS were significantly lower and BI scores were significantly higher in minocycline-treated patients . This pattern was already apparent on day 7 and day 30 of follow-up . Deaths , myocardial infa rct ions , recurrent strokes , and hemorrhagic transformations during follow-up did not differ by treatment group . Conclusions : Patients with acute stroke had significantly better outcome with minocycline treatment compared with placebo . The findings suggest a potential benefit of minocycline in acute ischemic stroke . GLOSSARY : ACE = angiotensin-converting enzyme ; ACEI = angiotensin-converting enzyme inhibitor ; BI = Barthel Index ; mRS = modified Rankin Scale ; NIHSS = NIH Stroke Scale ; PUD = peptic ulcer disease ; SU = sulfonylurea Newly hospitalized patients with stroke treated by indwelling catheters were assigned r and omly to 3 treatment groups . Group 1 ( 24 patients ) received 3 gm . ampicillin intramuscularly in divided doses 1 hour before , at the time of and 6 hours after insertion of the catheter . Group 2 ( 28 patients ) received daily 1 gm . ampicillin intramuscularly every 8 hours . Group 3 ( 26 patients ) was not subjected to any antimicrobial prophylaxis . Within 1 week after catheter insertion significant bacteriuria developed in 12.5 per cent of the patients in group 1 , 42.8 per cent in group 2 and 45.1 per cent in group 3 . The difference in the incidence between group 1 and either group 2 or 3 was statistically significant ( p less than 0.02 and p less than 0.01 , respectively ) . The mean number of strains ( plus or minus st and ard error of mean ) isolated per case of bacteriuria in group 3 ( 1.25 plus or minus 0.18 ) was significantly lower ( p less than 0.05 ) and antimicrobial resistant strains were fewer ( 4 of 15 ) than in group 2 ( 1.75 plus or minus 0.13 and 12 of 21 , respectively ) In comatose patients admitted to an ICU , particularly those with head injury , the incidence of early onset pneumonia is exceedingly high . We performed an open , prospect i ve , r and omized , and controlled clinical trial aim ing at the reduction of the incidence of ventilator-associated pneumonia in head-injured patients and patients with stroke requiring mechanical ventilation . One hundred patients were included because of head injury or coma caused by medical stroke and with Glasgow coma scores < or = 12 and mechanical ventilation > 72 h. Patients eligible for the study ( n = 50 ) received cefuroxime intravenously ( two 1,500-mg doses 12 h apart after intubation ) ( the cefuroxime group ) and 50 patients not receiving cefuroxime formed the control group . In the former group patients did not receive any other antibiotics before the end-point determination , whereas in the latter , 17 patients received prophylactic antibiotics as prescribed by the attending physician . The global incidence of microbiologically confirmed pneumonia was 37 % ( n = 37 ) ; 12 ( 24 % ) belonged to the cefuroxime group , and 25 ( 50 % ) belonged to the control group ( p = 0.007 ) . Early-onset pneumonia accounted for 70 % of all the pneumonia episodes ( n = 26 ) , eight ( 67 % ) belonging to the cefuroxime group , and 18 ( 72 % ) belonging to the control group ( p = 0.02 ) . In the control group , four of 17 ( 23 % ) patients receiving prior antibiotics developed pneumonia , whereas 21 of 33 ( 64 % ) patients who did not receive antibiotics developed pneumonia ( p = 0.016 ) . The multivariate analysis revealed that the duration of mechanical ventilation ( per each day ) was an independent risk factor significantly associated to the development of pneumonia . Furthermore , the use of cefuroxime and /or prior antibiotics in the control group , before the pneumonia episode , had a protective effect against its development . No differences were found with regard to mortality and morbidity when comparing the study population with the control group . Nevertheless , when comparing patients with pneumonia ( from both study and control groups ) with those without it , there was a decrease in total hospital stay ( 35 + /- 13 versus 25 + /- 14 d , p = 0.048 ) and ICU stay ( 20 + /- 11 versus 11 + /- 7 d , p = 0.001 ) . The study demonstrated that the administration of two single high doses 1,500 mg each of cefuroxime after the intubation of patients comatose because of head injury or medical stroke is an effective prophylactic strategy to decrease the incidence of ventilator-associated pneumonia BACKGROUND AND PURPOSE We sought to observe the type , timing , and frequency of complications occurring in hospitalized patients after an acute stroke . METHODS In a single hospital , we prospect ively identified a consecutive cohort of patients who were either admitted after an acute stroke or who suffered a stroke while already an inpatient ( n=613 ) . We retrieved the case notes for 607 ( 99 % ) of these strokes , and a single observer , using predefined diagnostic criteria , review ed the notes and recorded the type , timing , and frequency of complications that occurred during the inpatient period . We also measured the reliability of complication identification from case note review by comparing two observers on a sample of records . RESULTS Complications were recorded after 360 strokes ( 59 % ) ; the most common individual complications were falls ( complicating 22 % of all strokes ) , skin breaks ( 18 % ) , and urinary tract ( 16 % ) or chest ( 12 % ) infections . Miscellaneous " other " complications complicated 32 % of strokes . Seizures and chest infections occurred early , whereas depression and painful shoulder were later problems . Complications were more common in older patients , who were more disabled before their stroke and had suffered more severe strokes . We demonstrated moderate to good agreement between the two observers for most complications . CONCLUSIONS Complications after acute stroke are common , confirming that stroke rehabilitation requires active and knowledgeable medical input . Knowing the nature and timing of complications , together with the identification of high-risk patients , may be useful to those planning stroke services . The differences in our results and those previously reported , most notably for skin breaks , are probably due to the different methods used , in particular patient selection and diagnostic criteria for complications . Although complications may be useful as a measure of outcome in comparative studies ( eg , therapeutic trials and audit ) , the method ological difficulties in accurately and reliably measuring them must be addressed BACKGROUND following a stroke , morbidity and mortality is high , with aspiration pneumonia being a common complication . OBJECTIVES to determine the levels of colonisation by and isolation of aerobic Gram-negative bacteria ( AGNB ) in acute stroke patients and determine the effect of selective decontamination of the digestive tract ( SDD ) on oral flora and whether it reduces both morbidity and mortality after an acute stroke . DESIGN a prospect i ve , r and omised , placebo-controlled double blind trial . SETTING acute stroke assessment units of three hospitals in the northwest of Engl and . SUBJECTS 203 patients admitted to hospital following a first acute stroke . METHODS participants were r and omised to SDD oral gel or placebo . Swallow was assessed on admission to hospital , and oral swabs were obtained thrice weekly . Demographic and clinical data were recorded . RESULTS 203 patients ( 106 males and 97 females ) participated , of whom 20 died during their hospitalisation , 19 withdrew and full follow-up was obtained for the remaining 164 . A total of 122 AGNB were isolated in 105 sample s from 48 patients . Abnormal swallow on admission was found in 58 patients ( 29 % ) . A total of 34 patients carried a single gram-negative micro-organism that was present on one or more occasions . More than one AGNB was carried in 14 patients , and organisms were significantly more likely to be isolated from the placebo group than the active group during weeks 2 and 3 of treatment ( P = 0.034 , chi-squared ) . Seven patients in the placebo group and one in the treatment group developed pneumonia ( P = 0.029 , Fisher 's exact test ) . CONCLUSIONS high carriage of and colonisation by AGNB was found within this study , which was reduced by the addition of SDD . Although SDD reduced the presence of both organisms and documented episodes of pneumonia , mortality remained unchanged |
12,927 | 22,336,858 | In multiple sclerosis there was no evidence of a short-term or long-term effect of WBV on body balance , gait , muscle performance or quality of life .
AUTHORS ' CONCLUSIONS There is insufficient evidence of the effect of WBV training on functional performance of neurodegenerative disease patients .
Also , there is insufficient evidence regarding its beneficial effects on signs and symptoms of the disease , body balance , gait , muscle strength and quality of life compared to other active physical therapy or passive interventions in Parkinson 's disease or multiple sclerosis . | BACKGROUND Whole-body vibration ( WBV ) may be a complementary training to st and ard physical rehabilitation programmes and appears to have potential benefits in the sensorimotor system performance of patients with neurodegenerative diseases .
OBJECTIVES The aim of this review was to examine the efficacy of WBV to improve functional performance according to basic activities of daily living ( ADL ) in neurodegenerative diseases .
Additionally , we wanted to assess the possible effect on signs and symptoms of the disease , body balance , gait , muscle performance , quality of life and adverse events . | Background Fatigue or lack of interest can reduce the feasibility of intensive physical exercise in nursing home residents . Low-volume exercise interventions with similar training effects might be an alternative . The aim of this r and omised controlled trial was to investigate the feasibility of Whole Body Vibration ( WBV ) in institutionalised elderly , and its impact on functional capacity and muscle performance . Methods Twenty-four nursing home residents ( 15 female , 9 male ; mean age 77.5 ± 11.0 years ) were r and omised ( stratification for age , gender and ADL-category ) to 6 weeks static WBV exercise ( WBV+ , N = 13 ) or control ( only static exercise ; N = 11 ) . Outcome measures were exercise compliance , timed up- and -go , Tinetti-test , back scratch , chair sit- and -reach , h and grip strength and linear isokinetic leg extension . Results At baseline , WBV+ and control groups were similar for all outcome variables . Twenty-one participants completed the program and attended respectively 96 % and 86 % of the exercise sessions for the WBV+ and control groups . Training-induced changes in timed up- and -go and Tinetti-test were better for WBV+ compared to control ( p = 0.029 for timed up- and -go , p = 0.001 and p = 0.002 for Tinetti body balance and total score respectively ) . In an alternative analysis ( Worst Rank Score & Last Observation Carried Forward ) the differences in change remained significant on the Tinetti body balance and total score . No other significant differences in change between both groups were observed . Conclusion In nursing home residents with limited functional dependency , six weeks static WBV exercise is feasible , and is beneficial for balance and mobility . The supplementary benefit of WBV on muscle performance compared to classic exercise remains to be explored further OBJECTIVE To investigate the acute effects of long-term whole-body vibration on leg muscle performance and functional capacity in persons with multiple sclerosis . DESIGN A r and omized controlled trial . SUBJECTS Twenty-five patients with multiple sclerosis ( mean age 47.9 ± 1.9 years ; Exp and ed Disability Status Scale 4.3 ± 0.2 ) were assigned r and omly to whole-body vibration training ( n = 11 ) or to a control group ( n = 14 ) . METHODS The whole-body vibration group performed static and dynamic leg squats and lunges on a vibration platform ( 25 - 45 Hz , 2.5 mm amplitude ) during a 20-week training period ( 5 training sessions per 2-week cycle ) , and the control group maintained their usual lifestyle . PRE- , MID- ( 10 weeks ) and POST- ( 20 weeks ) knee-muscle maximal isometric and dynamic strength , strength endurance and speed of movement were measured using isokinetic dynamometry . Function was determined through the Berg Balance Scale , Timed Up and Go , Two-minute Walk Test and the Timed 25-Foot Walk Test . RESULTS Leg muscle performance and functional capacity were not altered following 10 or 20 weeks of whole-body vibration . CONCLUSION Under the conditions of the present study , the applied 20-week whole-body vibration exercise protocol did not improve leg muscle performance or functional capacity in mild- to moderately impaired persons with multiple sclerosis during and immediately after the training programme It is well known that applying vibrations to men influences multiple physiological functions . The authors analysed post effects of whole-body-vibration ( WBV ) on motor symptoms in Parkinson 's disease ( PD ) . Sixty-eight persons with PD were r and omly subdivided into one experimental and one control group . Motor symptoms were assessed by the UPDRS ( Unified Parkinson 's Disease Rating Scale ) motor score . A cross-over design was used to control treatment effects . The treatment consisted of 5 series of whole-body-vibration taking 60 seconds each . On average a highly significant ( p<0.01 ) improvement of 16.8 % in the UPDRS motor score was found in the treatment group . Only marginal changes ( p>0.05 ) were found in the control group . The cross-over procedure showed comparable treatment effects ( 14.7 % improvement after treatment ) . With respect to different symptom clusters only small changes were found in limb akinesia and cranial symptoms . By contrast , tremor and rigidity scores were improved by 25 % and 24 % , respectively . According to the structure of symptom changes it is unlikely that these effects are explainable on peripheral sensory level , exclusively . With respect to the findings of other studies one can speculate about changes in activation of the supplementary motor area and in neurotransmitter functions OBJECTIVE To investigate the efficacy of high-frequency whole-body vibration ( WBV ) on balancing ability in elderly women . DESIGN R and omized controlled trial . Subjects were r and omized to either the WBV intervention or the no-treatment control group . SETTING Community-living elderly women . PARTICIPANTS Sixty-nine elderly women aged 60 or above without habitual exercise . INTERVENTION Side alternating WBV at 20Hz with 3 minutes a day and 3 days a week for 3 months in the WBV intervention group . Those in control group remained sedentary with normal daily life for the whole study period . MAIN OUTCOME MEASURES Limits of stability in terms of reaction time , movement velocity , directional control , endpoint excursion , maximum excursion , and the functional reach test were performed at baseline and endpoint . RESULTS Significant enhancement of stability was detected in movement velocity ( P<.01 ) , maximum point excursion ( P<.01 ) , in directional control ( P<.05 ) . CONCLUSIONS WBV was effective in improving the balancing ability in elderly women . This also provides evidence to support our user-friendly WBV treatment protocol of 3 minutes a day for the elderly to maintain their balancing ability and reduce risks of fall OBJECTIVES To investigate the effects of 24 weeks of whole-body-vibration ( WBV ) training on knee-extension strength and speed of movement and on counter-movement jump performance in older women . DESIGN A r and omized , controlled trial . SETTING Exercise Physiology and Biomechanics Laboratory , Leuven , Belgium . PARTICIPANTS Eighty-nine postmenopausal women , off hormone replacement therapy , aged 58 to 74 , were r and omly assigned to a WBV group ( n=30 ) , a resistance-training group ( RES , n=30 ) , or a control group ( n=29 ) . INTERVENTION The WBV group and the RES group trained three times a week for 24 weeks . The WBV group performed unloaded static and dynamic knee-extensor exercises on a vibration platform , which provokes reflexive muscle activity . The RES group trained knee-extensors by performing dynamic leg-press and leg-extension exercises increasing from low ( 20 repetitions maximum ( RM ) ) to high ( 8RM ) resistance . The control group did not participate in any training . MEASUREMENTS Pre- , mid- ( 12 weeks ) , and post- ( 24 weeks ) isometric strength and dynamic strength of knee extensors were measured using a motor-driven dynamometer . Speed of movement of knee extension was assessed using an external resistance equivalent to 1 % , 20 % , 40 % , and 60 % of isometric maximum . Counter-movement jump performance was determined using a contact mat . RESULTS Isometric and dynamic knee extensor strength increased significantly ( P<.001 ) in the WBV group ( mean+/-st and ard error 15.0+/-2.1 % and 16.1+/-3.1 % , respectively ) and the RES group ( 18.4+/-2.8 % and 13.9+/-2.7 % , respectively ) after 24 weeks of training , with the training effects not significantly different between the groups ( P=.558 ) . Speed of movement of knee extension significantly increased at low resistance ( 1 % or 20 % of isometric maximum ) in the WBV group only ( 7.4+/-1.8 % and 6.3+/-2.0 % , respectively ) after 24 weeks of training , with no significant differences in training effect between the WBV and the RES groups ( P=.391 ; P=.142 ) . Counter-movement jump height enhanced significantly ( P<.001 ) in the WBV group ( 19.4+/-2.8 % ) and the RES group ( 12.9+/-2.9 % ) after 24 weeks of training . Most of the gain in knee-extension strength and speed of movement and in counter-movement jump performance had been realized after 12 weeks of training . CONCLUSION WBV is a suitable training method and is as efficient as conventional RES training to improve knee-extension strength and speed of movement and counter-movement jump performance in older women . As previously shown in young women , it is suggested that the strength gain in older women is mainly due to the vibration stimulus and not only to the unloaded exercises performed on the WBV platform OBJECTIVE To test whether training on a high-frequency ( 28Hz ) vibrating platform improves muscle power and bone characteristics in postmenopausal women . DESIGN R and omized controlled trial with 6-month follow-up . SETTING Outpatient clinic in a general hospital in Italy . PARTICIPANTS Twenty-nine postmenopausal women ( intervention group , n=14 ; matched controls , n=15 ) . INTERVENTION Participants stood on a ground-based oscillating platform for three 2-minute sessions for a total of 6 minutes per training session , twice weekly for 6 months . The controls did not receive any training . Both groups were evaluated at baseline and after 6 months . MAIN OUTCOME MEASURES Muscle power , calculated from ground reaction forces produced by l and ing after jumping as high as possible on a forceplate , cortical bone density , and biomarkers of bone turnover . RESULTS Over 6 months , muscle power improved by about 5 % in women who received the intervention , and it remained unchanged in controls ( P=.004 ) . Muscle force remained stable in both the intervention and control groups . No significant changes were observed in bone characteristics . CONCLUSION Reflex muscular contractions induced by vibration training improve muscle power in postmenopausal women Background Whole-body vibration ( WBV ) is a new type of exercise that has been increasingly tested for the ability to prevent bone fractures and osteoporosis in frail people . There are two currently marketed vibrating plates : a ) the whole plate oscillates up and down ; b ) reciprocating vertical displacements on the left and right side of a fulcrum , increasing the lateral accelerations . A few studies have shown recently the effectiveness of the up- and -down plate for increasing Bone Mineral Density ( BMD ) and balance ; but the effectiveness of the reciprocating plate technique remains mainly unknown . The aim was to compare the effects of WBV using a reciprocating platform at frequencies lower than 20 Hz and a walking-based exercise programme on BMD and balance in post-menopausal women . Methods Twenty-eight physically untrained post-menopausal women were assigned at r and om to a WBV group or a Walking group . Both experimental programmes consisted of 3 sessions per week for 8 months . Each vibratory session included 6 bouts of 1 min ( 12.6 Hz in frequency and 3 cm in amplitude with 60 ° of knee flexion ) with 1 min rest between bouts . Each walking session was 55 minutes of walking and 5 minutes of stretching . Hip and lumbar BMD ( g·cm-2 ) were measured using dual-energy X-ray absorptiometry and balance was assessed by the blind flamingo test . ANOVA for repeated measurements was adjusted by baseline data , weight and age . Results After 8 months , BMD at the femoral neck in the WBV group was increased by 4.3 % ( P = 0.011 ) compared to the Walking group . In contrast , the BMD at the lumbar spine was unaltered in both groups . Balance was improved in the WBV group ( 29 % ) but not in the Walking group . Conclusion The 8-month course of vibratory exercise using a reciprocating plate is feasible and is more effective than walking to improve two major determinants of bone fractures : hip BMD and balance This study was design ed to investigate the effects of vibration on muscle performance and mobility in a healthy , untrained , older population . Forty-three participants ( 23 men , 20 women , 66 - 85 y old ) performed tests of sit-to-st and ( STS ) , 5- and 10-m fast walk , timed up- and -go test , stair mobility , and strength . Participants were r and omly assigned to a vibration group , an exercise-withoutvibration group , or a control group . Training consisted of 3 sessions/wk for 2 mo . After training , the vibration and exercise groups showed improved STS ( 12.4 % , 10.2 % ) , 5-m fast walk ( 3.0 % , 3.7 % ) , and knee-extension strength ( 8.1 % , 7.2 % ) compared with the control ( p < 0.05 ) . Even though vibration training improved lower limb strength , it did not appear to have a facilitatory effect on functional-performance tasks compared with the exercise-without-vibration group . Comparable mobility and performance changes between the experimental groups suggest that improvements are linked with greater knee-extension strength and largely attributed to the unloaded squats performed by both exercise groups To determine whether 10 weeks of whole-body vibration ( WBV ) training has a significant effect on strength , muscle mass , muscle power , and mobility in older women , 26 subjects were r and omly assigned to a WBV training group ( n=13 ; mean age 79 years ) and a control ( CON ) group ( n=13 ; mean age 76 years ) . Maximal voluntary isometric contraction ( MVIC ) increased 38.8 % in the WBV group , without changes in the CON group . Electromyographic activity of the vastus medialis ( VM ) , the vastus lateralis , and the biceps femoris ( BF ) did not change in either group . Thigh muscle cross-sectional area increased significantly after training in VM ( 8.7 % ) and BF ( 15.5 % ) . Muscle power at 20 % , 40 % , and 60 % MVIC decreased from pre-test to post-test in the CON group ; however , WBV training prevented the decrease in the WBV group . Consequently , mobility , measured by the Timed Up and Go test , increased significantly after training ( 9.0 % ) only in the WBV group . Ten weeks of lower limb WBV training in older women produces a significant increase in muscle strength induced by thigh muscle hypertrophy , with no change in muscle power . The adaptations to WBV found in the present study may be of use in counteracting the loss of muscle strength and mobility associated with age-induced sarcopenia Recent studies have suggested that vibration therapy may have a positive influence on motor symptoms in individuals with Parkinson 's disease ( PD ) . However , quantitative evidence of these benefits is scarce , and the concept of " whole-body " vibration in these studies is vague . The objectives of the current study were to evaluate the influence of vibration on motor symptoms and functional measures in PD by delivering sound waves to the entire body . We delivered whole body sound wave vibration to 40 individuals with PD using a Physioacoustic Chair , a piece of equipment with speakers spaced throughout the chair permitting a series of programmed low frequency sound waves through the body . Using a parallel cross-over design we utilized the Unified Parkinson 's Disease Rating Scale ( UPDRS ) , quantitative gait assessment s , and a grooved pegboard for upper limb control . Improvements were seen in all symptom , motor control and functional outcome measures at the time of assessment . Specifically , a significant decrease in rigidity , and tremor were shown , as well as a significant increase in step length and improved speed on the grooved pegboard task . Results of this initial investigation provide support for vibration therapy as a non-pharmacological treatment alternative . Long-term benefits of vibration therapy will require further research This r and omized controlled trial investigated the effects of a 12 month whole body vibration training program on postural control in healthy older adults . Two hundred and twenty people were r and omly assigned to a whole body vibration group ( n=94 ) , a fitness group ( n=60 ) or a control group ( n=66 ) . The whole body vibration and fitness groups trained three times a week for 1 year . The vibration group performed exercises on a vibration platform and the fitness group performed cardiovascular , strength , balance and stretching exercises . Balance was measured using dynamic computerized posturography at baseline and after 6 and 12 months . Whole body vibration training was associated with reduced falls frequency on a moving platform when vision was disturbed and improvements in the response to toes down rotations at the ankle induced by the moving platform . The fitness group showed reduced falls frequency on the moving surface when vision was disturbed . Thus , whole body vibration training may improve some aspects of postural control in community dwelling older individuals Background and aims : Exercise may enhance the effect of alendronate on bone mineral density ( BMD ) and reduce chronic back pain in elderly women with osteoporosis . The aim of this study was to determine whether whole-body vibration exercise would enhance the effect of alendronate on lumbar BMD and bone turnover , and reduce chronic back pain in post-menopausal women with osteoporosis . Methods : Fifty post-menopausal women with osteoporosis , 55–88 years of age , were r and omly divided into two groups of 25 patients each : one taking alendronate ( 5 mg daily , ALN ) and one taking alendronate plus exercise ( ALN+EX ) . Exercise consisted of whole-body vibration using a Galileo machine ( Novotec , Pforzheim , Germany ) , at an intensity of 20 Hz , frequency once a week , and duration of exercise 4 minutes . The study lasted 12 months . Lumbar BMD was measured by dual energy X-ray absorptiometry ( Hologic QDR 1500W ) . Urinary cross-linked N-terminal telopeptides of type I collagen ( NTX ) and serum alkaline phos-phatase ( ALP ) levels were measured by enzyme-linked immunosorbent assay and st and ard laboratory techniques , respectively . Chronic back pain was evaluated by face scale score at baseline and every 6 months . Results : There were no significant differences in baseline characteristics , including age , body mass index , years since menopause , lumbar BMD , urinary NTX and serum ALP levels , or face scale score between the two groups . The increase in lumbar BMD and the reduction in urinary NTX and serum ALP levels were similar in the ALN and ALN+EX groups . However , the reduction in chronic back pain was greater in the ALN+EX group than in the ALN group . Conclusions : The results of this study suggest that whole-body vibration exercise using a Galileo machine appears to be useful in reducing chronic back pain , probably by relaxing the back muscles in post-menopausal osteoporotic women treated with alendronate Objective : To examine whether a whole-body vibration ( mechanical oscillations ) in comparison to a placebo administration leads to better postural control , mobility and balance in patients with multiple sclerosis . Design : Double-blind , r and omized controlled trial . Setting : Outpatient clinic of a university department of physical medicine and rehabilitation . Subjects : Twelve multiple sclerosis patients with moderate disability ( Kurtzke 's Exp and ed Disability Status Scale 2.5 - 5 ) were allocated either to the intervention group or to the placebo group . Interventions : In the intervention group a whole-body vibration at low frequency ( 2.0 - 4.4 Hz oscillations at 3-mm amplitude ) in five series of 1 min each with a 1-min break between the series was applied . In the placebo group a Burst-transcutaneous electrical nerve stimulation ( TENS ) application on the nondominant forearm in five series of 1 min each with a 1-min break between the series was applied as well . Main outcome measures : Posturographic assessment using the Sensory Organization Test , the Timed Get Up and Go Test and the Functional Reach Test immediately preceding the application , 15 min , one week and two weeks after the application . The statistical analysis was applied to the change score from preapplication values to values 15 min , one week and two weeks post intervention . Results : Compared with the placebo group the intervention group showed advantages in terms of the Sensory Organization Test and the Timed Get Up and Go Test at each time point of measurement after the application . The effects were strongest one week after the intervention , where significant differences for the change score ( p=0.041 ) were found for the Timed Get Up and Go Test with the mean score reducing from 9.2 s ( preapplication ) to 8.2 s one week after whole-body vibration and increasing from 9.5 s ( preapplication ) to 10.2 s one week after placebo application . The mean values of the posturographic assessment increased from 70.5 points ( preapplication ) to 77.5 points one week after whole body vibration and increased only from 67.2 points ( preapplication ) to 67.5 points one week after the placebo application . No differences were found for the Functional Reach Test . Conclusion : The results of this pilot study indicated that whole-body vibration may positively influence the postural control and mobility in multiple sclerosis patients 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 We investigated spontaneous effects of r and om whole-body vibration ( rWBV ) on postural control in Parkinsonian subjects . Effects were examined in biomechanical tests from a total of 52 patients divided equally into one experimental and one control group . Postural control was tested pre- and post-treatment in two st and ardized conditions ( narrow st and ing and t and em st and ing ) . The intervention was based on rWBV ( y : 3 mm , f : 6 Hz 1 Hz/sec ) consisting of 5 series lasting 60 seconds each . The main findings from this study were that ( 1 ) rWBV can improve postural stability in Parkinson 's disease ( PD ) spontaneously ( 2 ) these effects depend on the test condition . Based on the results of this study , rWBV can be regarded as an additional device in physical therapy in PD Patients with intention tremor due to multiple sclerosis ( MS ) exhibit an increased reliance on visual feedback in the sensorimotor control of slow goal -directed movements . In the present study , the use of proprioceptive information was investigated in MS patients with intention tremor compared to MS patients without tremor and healthy controls . Tendon vibration was applied to the wrist extensor muscles during a memory-guided slow wrist step-tracking task to investigate the use of muscle spindle afferent information in online movement control . A significant reduction of movement amplitude was induced by tendon vibration in all three groups , but the effect was found to be smaller in MS patients with tremor ( 28 % ) than in subjects without tremor ( 50 % ) . Vibration also induced an increase of overall tremor amplitude in the MS tremor group ; however , its effect on movement amplitude was not directly related to ( changes in ) tremor severity . The results suggest that the decreased online use of proprioceptive information in MS patients with tremor reflects an adaptation over time to cope with a tremor-related noisy background . Abnormalities in proprioceptive processing may explain why MS patients with tremor show an increased reliance on visual feedback for online motor control Objective : To examine the effectiveness of whole body vibration ( WBV ) on tone , muscle force , sensation and functional performance in people with multiple sclerosis . Design : A r and omized cross-over pilot study . Setting : Revive MS Support Therapy Centre . Glasgow , UK . Subjects : Sixteen people with multiple sclerosis were r and omly allocated to one of two groups . Intervention : Group 1 received four weeks of whole body vibration plus exercise three times per week , two weeks of no intervention and then four weeks of exercise alone three times per week . Group 2 were given the two treatment interventions in the reverse order to group 1 . Main measures : Ten-metre walk , Timed Up and Go Test , Modified Ashworth Scale , Multiple Sclerosis Spasticity Scale ( MSSS-88 ) , lower limb muscle force , Nottingham Sensory Assessment and Multiple Sclerosis Impact Scale ( MSIS-29 ) were used before and after intervention . Results : The exercise programme had positive effects on muscle force and well-being , but there was insufficient evidence that the addition of whole body vibration provided any further benefit . The Modified Ashworth Scale was generally unaffected by either intervention , although , for each group , results from the MSSS-88 showed whole body vibration and exercises reduced muscle spasms ( P = 0.02 ) . Although results for the 10-m walk and Timed Up and Go Test improved , this did not reach statistical significance ( P = 0.56 ; P = 0.70 , respectively ) . For most subjects sensation was unaffected by whole body vibration . Conclusion : Exercise may be beneficial to those with multiple sclerosis , but there is limited evidence that the addition of whole body vibration provides any additional improvements . Further larger scale studies into the effects of whole body vibration in people with multiple sclerosis are essential In the search of new strategies to improve the quality of life of Parkinson 's disease patients , recent work has reported an amelioration of Parkinsonian symptoms using Whole Body Vibration ( WBV ) . A double-blinded , placebo controlled design was used to evaluate the effect of a 12 WBV sessions-programme on a number of motor and clinical tests in 23 Parkinson 's disease patients . Patients were assigned to one of two groups , one receiving WBV and the other a placebo group . At the end of the programme as well as during intra-session evaluation , there was no difference between the experimental ( vibration ) and placebo groups in any outcomes . These results suggest that reported benefits of vibration are due to a placebo response BACKGROUND This r and omized controlled study investigated the effects of 1-year whole-body vibration ( WBV ) training on isometric and explosive muscle strength and muscle mass in community-dwelling men older than 60 years . METHODS Muscle characteristics of the WBV group ( n = 31 , 67.3 + /- 0.7 years ) were compared with those of a fitness ( FIT ) group ( n = 30 , 67.4 + /- 0.8 years ) and a control ( CON ) group ( n = 36 , 68.6 + /- 0.9 years ) . Isometric strength of the knee extensors was measured using an isokinetic dynamometer , explosive muscle strength was assessed using a counter movement jump , and muscle mass of the upper leg was determined by computed tomography . RESULTS Isometric muscle strength , explosive muscle strength , and muscle mass increased significantly in the WBV group ( 9.8 % , 10.9 % , and 3.4 % , respectively ) and in the FIT group ( 13.1 % , 9.8 % , and 3.8 % , respectively ) with the training effects not significantly different between the groups . No significant changes in any parameter were found in the CON group . CONCLUSION WBV training is as efficient as a fitness program to increase isometric and explosive knee extension strength and muscle mass of the upper leg in community-dwelling older men . These findings suggest that WBV training has potential to prevent or reverse the age-related loss in skeletal muscle mass , referred to as sarcopenia We explored the effects of r and om whole-body vibration on leg proprioception in Parkinson 's disease ( PD ) . In earlier studies it was found that this treatment leads to improved postural control in these patients . Thus , one could speculate that these effects result from modified proprioceptive capabilities . Twenty-eight PD patients were subdivided in one experimental and one control group . Proprioceptive performance was analyzed using a tracking task basing on knee extension and flexion movements . Treatment consisted of 5 series of r and om whole-body vibration taking 60 seconds each . Control subjects had a rest period instead . Prominent over- and undershooting errors were found in both groups representing proprioceptive impairments . No significant differences became evident , however , either between pre- and post-tests or between experimental and control group . One might therefore conclude that spontaneous improvements in postural control are not directly connected with proprioceptive changes . Nevertheless , one also should keep in mind the general aspects and difficulties of analyzing proprioception BACKGROUND whole body vibration ( WBV ) training appears to be an efficient alternative for conventional resistance training in older individuals . So far , no data exist about the vibratory effect on cardiorespiratory fitness . OBJECTIVES this r and omised controlled trial assessed the effects of 1-year WBV training on cardiorespiratory fitness and muscle strength in community-dwelling adults over the age of 60 . METHODS a total of 220 adults ( mean age 67.1 years ) were r and omly assigned to a WBV group , fitness group or control group . The WBV group exercised on a vibration platform , and the fitness group performed cardiovascular , resistance , balance and stretching exercises . The control group did not participate in any training . Heart rate was measured during a single WBV session . Peak oxygen uptake ( VO(2peak ) ) and time-to-peak exercise ( TPE ) were measured during progressive bicycle ergometry . Muscle strength was assessed by a dynamometer . RESULTS heart rate increased significantly during WBV training . After 1 year , VO(2peak ) , TPE and muscle strength increased significantly in the WBV and fitness groups . Both training groups improved similarly in VO(2peak ) and muscle strength . The fitness group improved significantly more in TPE than the WBV group . CONCLUSION WBV training in community-dwelling elderly appears to be efficient to improve cardiorespiratory fitness and muscle strength OBJECTIVE The objective of this study was to investigate efficacy of a whole-body vibration ( WBV ) intervention on functional performance of community-dwelling older adults . DESIGN The study was design ed as a r and omized controlled trial . SETTING The setting was in community centers . SUBJECTS There were 37 total subjects ( 21 women and 16 men ) ( age 69 + /- 8 years ; mean + /- st and ard deviation ) . INTERVENTION Participants were r and omized to a WBV intervention ( INT ) group and control ( CON ) group . Whole-body vibration was administered for five 1-minute bouts per session , 3 days per week , for 6 weeks . The CON group was asked not to commence any form of physical training . OUTCOME MEASURES Functional performance was measured with the timed-up- and -go-test ( TUG ) and sit-to-st and -test ( STS ) . RESULTS After WBV , TUG and STS time was less for INT than CON ( INT , TUG 7.6 + /- 0.3 seconds , STS 11.9 + /- 2.0 seconds ; CON , TUG 8.6 + /- 0.9 , STS 13.5 + /- 1.1 seconds ; p < 0.05 ) . Within INT , TUG improved 0.9 + /- 0.4 seconds ; p = 0.01 and STS improved 3.0 + /- 0.9 seconds ; p = 0.05 ) . CONCLUSIONS The efficacy of this WBV intervention was established . Functional performance improvement after WBV may be attributed to a number of biological mechanisms that remain speculative . Further research is required to mechanistically underst and the effects of WBV on older adults The aim of this study was to investigate the effects of vibration exercise on postural steadiness performance in a healthy , older population . Forty-three healthy , older participants ( 23 men and 20 women , aged 73.5+/-4.5 yr ) were r and omly assigned to either a vibration group ( VIB ) , an exercise without vibration group ( EX ) or a control group ( CONT ) . The VIB and EX groups undertook static and dynamic bodyweight exercises three times per week for eight weeks . Static balance was assessed using a one-legged postural steadiness ( OLPS ) test . This test was performed prior to and immediately after the training period . OLPS improved significantly for the VIB intervention after eight weeks training ( p<0.05 ) compared to the EX and CONT groups . The improvements in OLPS were significantly affected by the baseline values , with the largest changes evident for VIB participants with a poorer initial score ( p<0.01 ) . Vibration exercise can contribute to improved static one-legged balance in a healthy , older population . As improvements in OLPS were related to baseline values , vibration exercise as an intervention would appear to serve the most benefit for those that exhibit diminished postural control OBJECTIVE To investigate the effects of whole body vibration in the elderly . DESIGN R and omized controlled trial . SETTING Nursing home . PARTICIPANTS Forty-two elderly volunteers . INTERVENTIONS Six-week vibration intervention plus physical therapy ( PT ) ( n=22 ) or PT alone ( n=20 ) . MAIN OUTCOME MEASURES We assessed gait and body balance using the Tinetti test ( maximum scores of 12 for gait , 16 for body balance , 28 for global score ) , motor capacity using the Timed Up & Go ( TUG ) test , and health-related quality of life ( HRQOL ) using the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) . RESULTS After 6 weeks , the vibration intervention group improved by a mean + /- st and ard deviation of 2.4+/-2.3 points on the gait score compared with no score change in the control group ( P < .001 ) . The intervention group improved by 3.5+/-2.1 points on the body balance score compared with a decrease of 0.3+/-1.2 points in the control group ( P < .001 ) . TUG test time decreased by 11.0+/-8.6 seconds in the treated group compared with an increase of 2.6+/-8.8 seconds in the control group ( P < .001 ) . The intervention group had significantly greater improvements from baseline on 8 of 9 items on the SF-36 compared with the control group . CONCLUSIONS Controlled whole body vibration can improve elements of fall risk and HRQOL in elderly patients Background and Purpose : Whole-body vibration ( WBV ) is a relatively new form of exercise training that may influence muscle performance . This study investigated the acute effects of high- ( 26 Hz ) and low- ( 2 Hz ) frequency WBV on isometric muscle torque of the quadriceps and hamstrings in persons with multiple sclerosis . Participants and Method : Fifteen individuals ( mean age = 54.6 years , SD = 9.6 ) with multiple sclerosis and Exp and ed Disability Status Scale scores ranging from 0 to 6.5 ( mean = 4.2 , SD = 2.3 ) participated in this r and omized , crossover study . After baseline measures of isometric quadriceps and hamstring muscle torque , subjects were exposed to 30 seconds of WBV at either 2 or 26 Hz . Torque values were measured again at one , 10 , and 20 minutes after vibration . Subjects returned one week later to repeat the same protocol at the alternate vibration frequency . Results : There were no significant differences in isometric torque production between the 2- and 26-Hz WBV conditions . There was also no significant difference between baseline torque values and those measured at one , 10 , and 20 minutes after either vibration exposure . However , there was a consistent trend of higher torque values after the 26-Hz WBV when compared with the 2-Hz condition for both quadriceps and hamstring muscles . Discussion and Conclusion : Although not statistically significant , peak torque values for both quadriceps and hamstring muscles were consistently higher after 30 seconds of WBV at 26 vs 2 Hz . Whether WBV presents a viable treatment option as either a warm-up activity or a long-term exercise intervention is yet to be determined . Future studies should include a wider variety of WBV parameters and the use of functional outcome measures UNLABELLED High-frequency mechanical strain seems to stimulate bone strength in animals . In this r and omized controlled trial , hip BMD was measured in postmenopausal women after a 24-week whole body vibration ( WBV ) training program . Vibration training significantly increased BMD of the hip . These findings suggest that WBV training might be useful in the prevention of osteoporosis . INTRODUCTION High-frequency mechanical strain has been shown to stimulate bone strength in different animal models . However , the effects of vibration exercise on the human skeleton have rarely been studied . Particularly in postmenopausal women-who are most at risk of developing osteoporosis-r and omized controlled data on the safety and efficacy of vibration loading are lacking . The aim of this r and omized controlled trial was to assess the musculoskeletal effects of high-frequency loading by means of whole body vibration ( WBV ) in postmenopausal women . MATERIAL S AND METHODS Seventy volunteers ( age , 58 - 74 years ) were r and omly assigned to a whole body vibration training group ( WBV , n = 25 ) , a resistance training group ( RES , n = 22 ) , or a control group ( CON , n = 23 ) . The WBV group and the RES group trained three times weekly for 24 weeks . The WBV group performed static and dynamic knee-extensor exercises on a vibration platform ( 35 - 40 Hz , 2.28 - 5.09 g ) , which mechanically loaded the bone and evoked reflexive muscle contractions . The RES group trained knee extensors by dynamic leg press and leg extension exercises , increasing from low ( 20 RM ) to high ( 8 RM ) resistance . The CON group did not participate in any training . Hip bone density was measured using DXA at baseline and after the 6-month intervention . Isometric and dynamic strength were measured by means of a motor-driven dynamometer . Data were analyzed by means of repeated measures ANOVA . RESULTS No vibration-related side effects were observed . Vibration training improved isometric and dynamic muscle strength ( + 15 % and + 16 % , respectively ; p < 0.01 ) and also significantly increased BMD of the hip ( + 0.93 % , p < 0.05 ) . No changes in hip BMD were observed in women participating in resistance training or age-matched controls ( -0.60 % and -0.62 % , respectively ; not significant ) . Serum markers of bone turnover did not change in any of the groups . CONCLUSION These findings suggest that WBV training may be a feasible and effective way to modify well-recognized risk factors for falls and fractures in older women and support the need for further human studies Sarcopenia and osteoporosis represent a growing public health problem . We studied the potential benefit of whole-body vibration ( WBV ) training given a conventional or a high dose of daily vitamin D supplementation in improving strength , muscle mass , and bone density in postmenopausal women . In a 2 × 2 factorial- design trial , 113 institutionalized elderly females aged over 70 years ( mean age 79.6 years ) were r and omly assigned either to a WBV or a no-training group , receiving either a conventional dose ( 880 IU/day ) or a high dose ( 1600 IU/day ) of vitamin D(3 ) . The primary aim was to determine the effects of 6 months of WBV and /or vitamin D supplementation on isometric and dynamic strength , leg muscle mass , and hip bone mineral density ( BMD ) . Additionally , the increase in 25-hydroxyvitamin D [ 25(OH)D ] levels between conventional and high-dose supplementation was compared . After 6 months of treatment , dynamic muscle strength , hip BMD , and vitamin D serum levels improved significantly in all groups , whereas isometric strength and muscle mass did not change . When compared with no training , the WBV program did not result in additional improvements . When compared with 880 IU , a high dose of 1600 IU of vitamin D did result in higher serum vitamin D levels but did not result in additional improvements . In institutionalized women older than 70 years , the WBV training protocol tested is not more efficient in enhancing muscle mass , strength , and hip BMD compared with vitamin D supplementation . A higher dose of 1600 IU of vitamin D does not provide additional musculoskeletal benefit in this population compared with conventional doses In this study , we compared the efficacy of 8 months of low-frequency vibration and a walk-based program in health-related fitness . Twenty-seven postmenopausal women were r and omly assigned into two groups : whole-body vibration ( WBV ) group ( n = 18 ) performed three times/week a static exercise on a vibration platform ( 6 sets of 1-min with 1 min of rest , with a 12.6 Hz of frequency and an amplitude of 3 mm ) ; walk-based program ( WP ) group ( n = 18 ) performed three times/week a 60-min of walk activity at 70–75 % of maximal heart rate . A health-related battery of tests was applied . Maximal unilateral concentric and eccentric isokinetic torque of the knee extensors was recorded by an isokinetic dynamometer . Physical fitness was measured using the following tests : vertical jump test , chair rise test and maximal walking speed test over 4 m. Maximal unilateral isokinetic strength was measured in the knee extensors in concentric actions at 60 and 300 ° /s , and eccentric action at 60 ° /s . After 8 months , the WP improved the time spent to walk 4 m ( 20 % ) and to perform the chair rise test ( 12 % ) compared to the WBV group ( P = 0.006 , 0.002 , respectively ) . In contrast , the comparison of the changes in vertical jump showed the higher effectiveness of the vibratory exercise in 7 % ( P = 0.025 ) . None of exercise programs showed change on isokinetic measurements . These results indicate that both programs differed in the main achievements and could be complementary to prevent lower limbs muscle strength decrease as we age [ IS RCT N76235671 ] OBJECTIVE To evaluate the feasibility of a new functional tasks exercise program , design ed to improve functional performance of community-dwelling older women , by comparing it with a resistance exercise program . DESIGN A 12-week , r and omized , single-blind pilot study . SETTING A community leisure center . PARTICIPANTS Twenty-four community-dwelling , medically stable women ( mean age , 74.6+/-4.8 y ) were r and omized to the functional tasks exercises ( function group ) or the resistance exercises ( resistance group ) . Three participants withdrew from the study . INTERVENTIONS Exercises were given 3 times weekly for 12 weeks . The functional tasks exercise program aim ed to improve daily tasks in the domains first affected in older adults , whereas the resistance exercise program focused on strengthening the muscle groups that are important for functional performance . MAIN OUTCOME MEASURES Participant satisfaction with the exercises , Assessment of Daily Activity Performance ( ADAP ) , and , as a secondary outcome , muscle strength and power . RESULTS Exercise adherence was 81 % in the function group and 90 % in the resistance group . Participants reported greater satisfaction with the resistance exercises than with the functional exercises . The ADAP total score improved with time ( P = .001 ; mean change function group , 7.5 U ; 95 % confidence interval [ CI ] , 2.1 - 12.8 ; resistance group , 2.8 U , 95 % CI , -0.4 to 5.9 ) , as did isometric knee extensor strength ( P = .001 ; mean change function group , 6.4 % ; 95 % CI , -1.6 to 14.5 ; resistance group , 14.4 % ; 95 % CI , 6.4 - 22.2 ) . Testing for differences in outcomes between the 2 groups showed no statistically significant differences . CONCLUSIONS The functional tasks exercise program is feasible and shows promise of being more effective for functional performance than a resistance exercise program . A r and omized controlled trial with a larger sample size is needed to test the difference between the 2 programs Falls in the elderly constitute a growing public health problem . This r and omized controlled trial investigated the potential benefit of 6 months of whole body vibration ( WBV ) training and /or vitamin D supplementation on balance , functionality and estimated fall risk in institutionalized elderly women . A total of 113 women ( mean age : 79.6 ) were r and omly assigned to either a WBV or a no-training group , receiving either a conventional dose ( 880 IU/d ) or a high dose ( 1600 IU/d ) of vitamin D3 . The WBV group performed exercises on a vibration platform 3 × /week . Balance was evaluated by computerized posturography . Functionality was assessed by 10 m walk test , Timed up and Go ( TUG ) performance and endurance capacity ( Shuttle Walk ) . Fall risk was determined with the Physiological Profile Assessment . Performance on the 10 m walk test and on TUG improved over time in all groups . For none of the parameters , high-dose vitamin D result ed in a better performance than conventional dosing . The improvements in the WBV group in endurance capacity , walking at preferred speed , and TUG were significantly larger than the changes with supplementation alone . No additional benefit of WBV training could be detected on fall risk and postural control , although sway velocity and maximal isometric knee extension strength improved only in the WBV group . This trial showed that a high-dose vitamin D supplementation is not more efficient than conventional dosing in improving functionality in institutionalized elderly . WBV training on top of vitamin D supplementation provided an added benefit with regard to walking , TUG performance , and endurance capacity Bedient , AM , Adams , JB , Edwards , DA , Serravite , DH , Huntsman , E , Mow , SE , Roos , BA , and Signorile , JF . Displacement and frequency for maximizing power output result ing from a bout of whole-body vibration . J Strength Cond Res 23(6 ) : 1683 - 1687 , 2009-Whole-body vibration ( WBV ) has been shown to be effective for increasing lower-body power ; however , the combination of frequency , displacement , and duration that elicits the best acute response has yet to be determined . The purpose of this study was to identify the protocol eliciting the greatest improvement in power after an acute bout of WBV . Forty men and women participated in this study , in which 8 different combinations of 30 , 35 , 40 , and 50 Hz with 2-mm and 5-mm displacements were tested over 3 days . For all protocol s , r and omized to reduce potential order effects , subjects underwent 30 seconds of WBV while holding an isometric squat at a knee angle of 2.27 rad . Power was assessed by countermovement jumps . Subjects performed 3 jumps before WBV , immediately afterward , and 1 , 5 , and 10 minutes later . The highest normalized peak power ( nPP ) at each time point was determined using a 4 ( frequency ) × 2 ( displacement ) × 5 ( time ) repeated- measures analysis of variance . Significant effects were seen for frequency ( p ≤ 0.026 ) and time ( p ≤ .0001 ) . Post hoc analyses revealed that the 30-Hz condition ( 1.010 ± 0.003 ) produced a higher nPP than 35 Hz ( 1.00 ± 0.003 , p ≤ 0.026 ) and 40 Hz ( 1.002 ± 0.002 , p ≤ 0.028 ) but not 50 Hz ( 1.004 ± .002 ) . We also found a significantly higher nPP for the 1-minute post-treatment time point ( 1.011 ± .0003 ) vs. all other time points ( p ≤ 0.006 ) . Our data show that an acute WBV bout can significantly increase power output at 1 minute post-treatment across all frequencies and displacements , although 30 Hz appears to have a greater effect on power output than either 35 Hz or 40 Hz , but not 50 Hz , at all post-treatment time points Purpose . It was hypothesised that lumbar vibration stimulation applied by a vibratory orthosis improves balance in people with Parkinson 's disease ( PD ) . Methods . The overall stability index and the percent of elapsed time in different zones and quadrants on the platform of Biodex balance system were evaluated . General conditions of eyes-open and eyes-close , each with two situations of motors On and motors Off of vibratory orthosis were considered . Results . Balance in PD patients improved in eyes-open condition rather than eyes-close . The balance also improved in eyes-open condition with motors On rather than that in motors Off . In eyes-close condition , balance was lesser in motors On than that in motors Off situation . The results also suggest that in PD patients , body trajectories on the platform of Biodex balance system follow a r and om-like chaotic behaviour . Conclusions . A new orthosis in rehabilitation of PD patients was introduced to enhance balance and decrease risk of fall . It promotes new ideas for rehabilitation of similar neurological diseases . The possibility of enhancing balance in PD patients in a short-term setting was evaluated . Results showed balance enhancement in PD patients in eyes-open condition . However , in eyes-close condition , we are not sure of its effectiveness Furness , TP and Maschette , WE . Influence of whole body vibration platform frequency on neuromuscular performance of community-dwelling older adults . J Strength Cond Res 23(5 ) : 1508 - 1513 , 2009-The purpose of this study was to progressively overload vibration platform frequency to describe sea-saw whole body vibration influence on neuromuscular performance of community-dwelling older adults . Seventy-three community-dwelling older adults ( aged 72 ± 8 years ) were r and omly assigned to 4 groups ( zero , one , 2 , and 3 whole body vibration sessions per week ) . Quantifiers of neuromuscular performance such as the 5-Chair St and s test , the Timed Up and Go ( TUG ) test , and the Tinetti test were recorded . Furthermore , Health-related quality of life was qualified with the SF-36 Health Survey . A 6-week whole body vibration intervention significantly improved the quantifiers of neuromuscular performance in a community-dwelling older adult sample . Whole body vibration was shown to significantly reduce time taken to complete the 5-Chair St and s test ( p < 0.05 ) and the TUG test ( p < 0.05 ) . Tinetti test scores significantly improved ( p < 0.05 ) . as did all components of health-related quality of life ( p < 0.05 ) . Overall , progressively overloaded frequency elicited more beneficial improvement for the 3 whole body vibration sessions per week group . It was concluded that progressively overloaded frequency was effective in improving quantifiable measures of neuromuscular performance in the sample and that practitioners may confidently prescribe 3 whole body vibration sessions per week with more precise knowledge of the effects of whole body vibration on neuromuscular performance and health-related quality -of-life effects It was hypothesized that both vibration frequency and muscle length modulate the strengthening of muscles that is assumed to result from whole-body vibration ( WBV ) . Length of knee extensor muscles during vibration is affected by the knee joint angle ; the lengths of the knee extensors increase with more flexed knee joint angles . In an intervention study 28 volunteers were r and omly assigned to 1 of 4 groups . Each group received 4 weeks of WBV at 1 of 3 different frequencies ( 20 , 27 , or 34 Hz ) or 1 of 2 different lengths of knee extensors . Voluntary , isometric knee extension moment-angle relationship was determined . Initially , stronger subjects reacted differently to WBV than weaker participants . In stronger subjects knee extension moment did not improve ; in the weaker subjects considerable improvements were observed ranging from 10 to 50 % . Neither vibration frequency nor muscle length during the intervention affected the improvements . In addition to strength , the knee joint angle at which the maximal joint moment was generated ( optimal joint angle ) was affected . When trained at short muscle lengths , optimal angle shifted to more extend joint position . WBV training at long muscle lengths tended to induce an opposite shift . The amount of this shift tended to be influenced by vibration frequency ; the lower the vibration frequency the larger the shift . Shifts of optimal lengths occurred in both weaker and stronger subjects . This study shows that muscle length during training affects the angle of knee joint at which the maximal extension moment was generated . Moreover , in weaker subjects WBV result ed in higher maximal knee joint extension moments . Vibration frequency and muscle length during vibration did not affect this joint moment gain Background and Purpose : Vibration training is a relatively new exercise intervention . This study investigated the effects of vibration exercise on strength ( force-producing capacity ) and power in older adults who are healthy . Participants and Methods : Thirty participants ( mean age=73.7 years , SD=4.6 ) were r and omly assigned to a vibration exercise training ( VIB ) group or an exercise without vibration training ( EX ) group . The interventions consisted of 3 sessions per week for 8 weeks . Outcome measures included isokinetic flexor and extensor strength and power of the hip , knee , and ankle . Results : The VIB group significantly improved ankle plantar flexor strength and power compared with the EX group . However , there were no significant differences between the VIB and EX groups for knee flexor or extensor strength . Discussion and Conclusion : Vibration training contributed to an increase in plantar flexor strength and power . However , the strength gains for the knee and hip flexors and extensors for the VIB group and the EX group were comparable . Future vibration protocol s should explore different body positions to target muscles higher up on the leg The purpose of this study was to assess the effect of whole body vibration ( WBV ) exercise on muscle strength and proprioception in female patients with osteoarthritis in the knee ( knee-OA ) . A single blinded , r and omised , controlled trial was performed in an outpatient clinic on 52 female patients diagnosed with knee-OA ( mean age 60.4 years+/-9.6 ) . They were r and omly assigned to one of 3 groups : 1 . WBV-exercise on a stable platform ( VibM ; n=17 ( mean age , 61.5+/-9.2 ) ) , WBV-exercise on a balance board ( VibF ; n=18 ( mean age , 58.7+/-11.0 ) ) , or control group ( Con ; n=18 ( mean age , 61.1+/-8.5 ) ) . The WBV groups trained twice a week for 8 weeks , with a progressively increasing intensity . The WBV groups performed unloaded static WBV exercise . The following were measured : knee muscle strength ( extension/flexion ) and proprioception ( threshold for detection of passive movement ( TDPM ) ) . Self-reported disease status was measured using WOMAC . It was found that muscle strength increased significantly ( p<0.001 ) in VibM compared to Con . Isometric knee-extension significantly increased ( p=0.021 ) in VibM compared to Con . TDPM was significantly improved ( p=0.033 ) in VibF compared to Con , while there was a tendency ( p=0.051 ) for VibM to perform better compared to Con . There were no effects in the self-reported disease status measures . This study showed that the WBV-exercise regime on a stable platform ( VibM ) yielded increased muscle strength , while the WBV-exercise on a balance board ( VibF ) showed improved TDPM . The WBV-exercise is a time-saving and safe method for rehabilitation of women with knee-OA UNLABELLED A 1-year prospect i ve , r and omized , double-blind , and placebo-controlled trial of 70 postmenopausal women demonstrated that brief periods ( < 20 minutes ) of a low-level ( 0.2 g , 30 Hz ) vibration applied during quiet st and ing can effectively inhibit bone loss in the spine and femur , with efficacy increasing significantly with greater compliance , particularly in those subjects with lower body mass . INTRODUCTION Indicative of the anabolic potential of mechanical stimuli , animal models have demonstrated that short periods ( < 30 minutes ) of low-magnitude vibration ( < 0.3 g ) , applied at a relatively high frequency ( 20 - 90 Hz ) , will increase the number and width of trabeculae , as well as enhance stiffness and strength of cancellous bone . Here , a 1-year prospect i ve , r and omized , double-blind , and placebo-controlled clinical trial in 70 women , 3 - 8 years past the menopause , examined the ability of such high-frequency , low-magnitude mechanical signals to inhibit bone loss in the human . MATERIAL S AND METHODS Each day , one-half of the subjects were exposed to short- duration ( two 10-minute treatments/day ) , low-magnitude ( 2.0 m/s2 peak to peak ) , 30-Hz vertical accelerations ( vibration ) , whereas the other half stood for the same duration on placebo devices . DXA was used to measure BMD at the spine , hip , and distal radius at baseline , and 3 , 6 , and 12 months . Fifty-six women completed the 1-year treatment . RESULTS AND CONCLUSIONS The detection threshold of the study design failed to show any changes in bone density using an intention-to-treat analysis for either the placebo or treatment group . Regression analysis on the a priori study group demonstrated a significant effect of compliance on efficacy of the intervention , particularly at the lumbar spine ( p = 0.004 ) . Posthoc testing was used to assist in identifying various subgroups that may have benefited from this treatment modality . Evaluating those in the highest quartile of compliance ( 86 % compliant ) , placebo subjects lost 2.13 % in the femoral neck over 1 year , whereas treatment was associated with a gain of 0.04 % , reflecting a 2.17 % relative benefit of treatment ( p = 0.06 ) . In the spine , the 1.6 % decrease observed over 1 year in the placebo group was reduced to a 0.10 % loss in the active group , indicating a 1.5 % relative benefit of treatment ( p = 0.09 ) . Considering the interdependence of weight , the spine of lighter women ( < 65 kg ) , who were in the highest quartile of compliance , exhibited a relative benefit of active treatment of 3.35 % greater BMD over 1 year ( p = 0.009 ) ; for the mean compliance group , a 2.73 % relative benefit in BMD was found ( p = 0.02 ) . These preliminary results indicate the potential for a noninvasive , mechanically mediated intervention for osteoporosis . This non-pharmacologic approach represents a physiologically based means of inhibiting the decline in BMD that follows menopause , perhaps most effectively in the spine of lighter women who are in the greatest need of intervention OBJECTIVE To compare the effects of whole body vibration ( WBV ) and conventional physiotherapy ( PT ) on levodopa-resistant disturbances of balance and gait in idiopathic Parkinson 's disease ( PD ) . DESIGN R and omized controlled rater-blinded trial comparing 2 active interventions , final follow-up assessment 4 weeks after termination of active intervention . SETTING Specialized referral center , hospitalized care . PARTICIPANTS Patients with PD and dopa-resistant imbalance on stable dopamine replacement medication ( N=27 ) were r and omized ( intent-to-treat population ) to receive WBV ( n=13 ) or conventional PT ( controls , n=14 ) . Twenty-one patients ( per protocol population ) completed follow-up ( 14 men , 7 women ; mean age , 73.8 y ; age range , 62 - 84 y ; mean disease duration , 7.2 y ; mean dopa-equivalent dose , 768 mg/d ) . INTERVENTION Subjects were r and omized to receive 30 sessions ( two 15-min sessions a day , 5 days a week ) of either WBV on an oscillating platform or conventional balance training including exercises on a tilt board . Twenty-one subjects ( 10 with WBV , 11 controls ) were available for follow-up 4 weeks after treatment termination . MAIN OUTCOME MEASURES The primary measure was Tinetti Balance Scale score . Secondary clinical ratings included st and -walk-sit test , walking velocity , Unified Parkinson 's Disease Rating Scale ( section III motor examination ) score , performance in the pull test , and dynamic posturography . RESULTS The Tinetti score improved from 9.3 to 12.8 points in the WBV group and from 8.3 to 11.7 in the controls . All secondary measures , except posturography , likewise improved at follow-up compared with baseline in both groups . Quantitative dynamic posturography only improved in patients with WBV ( 1937 - 1467 mm ) whereas there was no significant change in controls ( 1832 - 2030 mm ) . CONCLUSIONS Equilibrium and gait improved in patients with PD receiving conventional WBV or conventional PT in the setting of a comprehensive rehabilitation program . There was no conclusive evidence for superior efficacy of WBV compared with conventional balance training |
12,928 | 25,669,840 | The findings from this review suggest that health education has a beneficial impact on knowledge and underst and ing of schistosomiasis within the target groups . | An estimated 129 million people are infected with urogenital schistosomiasis in sub-Saharan Africa .
Current control recommendations endorse mass administration of praziquantel .
Health education is an important component of effective schistosomiasis prevention and control , but there has been limited research on its effectiveness .
This paper review s the effectiveness of health education as an intervention in the prevention and control of urogenital schistosomiasis in sub-Saharan Africa . | The objective of this study was to assess the effect of health education in the control of bilharziasis , as a part of an investigation on anti-urinary bilharziasis campaign in Niger . We carried out a survey in two groups of endemic villages on the Niger , one group of villages where there are health education campaigns ( target villages ) and a control village ( no education campaign ) . Five hundred and seventy-seven people were interviewed in the area . The bilharziasis project has been the main source of information on bilharziasis of people in the project zone . The awareness of measures to fight against bilharziasis has been moderate . Indeed , 46.6 % of people interrogated in the project area could n't cite any means for containing bilharziasis . In the area of intervention , 41.5 % of people interrogated were unaware of the intervention of an intermediate host in the transmission of the urinary bilharziasis . The notion of reinfestation remains little known . Behaviours that favour the illness were ignored by 1/3 of people interrogated in the project area . However , there was an increase in knowledge about the illness in the program zone in comparison with the control area . Despite the increase in knowledge level , changes in behaviour in relation to the illness remained low . Risky behaviour continued in about 2/3 of people interrogated . Only 33 % of persons of the project area declared having adopted at least a single good behaviour . Changes of behaviour are slow to take place . Activities of health education must be sustained throughout a long period of time for sustainable profits of control actions to occur Over a period of one school year a study was carried out into the feasibility and effectiveness of introducing active teaching methods into primary schools in Tanzania with a view to enhancing health education . The Lushoto Enhanced Health Education Project had as a focus personal hygiene with reference to the control of schistosomiasis and helminth infections . When a r and omly selected group of children were compared with a comparison group there was evidence of changes in both knowledge and health-seeking behaviour . The passing of messages from children to the community met with mixed results . The observed changes were still evident over 1 year after the project had ended Objective : To determine the association between female genital Schistosoma haematobium infection and HIV . Design and methods : A cross-sectional study with a 1-year follow-up . Gynecological and laboratory investigations were performed for S. haematobium and HIV . Sexually transmitted infections , demographic and urogenital history were analysed as confounders . The participants were 527 sexually active , non-pregnant , non-menopausal women between the ages of 20 and 49 years . The setting was a rural Zimbabwean community where S. haematobium related lesions were found in 46 % of the women , HIV in 29 % and herpes simplex type- 2 ( HSV-2 ) in 65 % . Results : In permanent residents ( > 3 years residency ) , HIV was found in 41 % ( 29/70 ) of women with laboratory proven genital schistosomiasis as opposed to 26 % HIV positive ( 96/375 ) in the schistosomal ova negative group [ odds ratio ( OR ) , 2.1 ; 95 % confidence interval ( CI ) , 1.2–3.5 ; P = 0.008 . In multivariate analysis S. haematobium infection of the genital mucosa was significantly associated with HIV seropositivity ( adjusted OR , 2.9 ; 95 % CI , 1.11–7.5 ; P = 0.030 ) . All seven women who became HIV positive during the study period ( seroincidence 3.1 % ) had signs of S. haematobium at baseline . In accordance with other studies HIV was significantly associated with HSV-2 ( OR , 3.0 ; 95 % CI , 1.7–5.3 ; P < 0.001 ) , syphilis and human papillomavirus . The highest HIV prevalence ( 45 % ) was found in the 25–29 years age group . Conclusion : Women with genital schistosomiasis had an almost three-fold risk of having HIV in this rural Zimbabwean community . Prospect i ve studies are needed to confirm the association |
12,929 | 31,870,327 | Results of the meta- analysis suggest that mpMRI is a sensitive tool to diagnose prostate cancer . | The application of multiparametric magnetic resonance imaging ( mpMRI ) for diagnosis of prostate cancer has been recommended by the European Association of Urology ( EAU ) , National Comprehensive Cancer Network ( NCCN ) , and European Society of Urogenital Radiology ( ESUR ) guidelines .
The purpose of this study is to systematic ally review the literature on assessing the accuracy of mpMRI in patients with suspicion of prostate cancer . | Background : The European Society of Urogenital Radiology has built the Prostate Imaging Reporting and Data System ( PI-RADS ) for st and ardizing the diagnosis of prostate cancer ( PCa ) . This study evaluated the PI-RADS diagnosis method in patients with prostate-specific antigen ( PSA ) < 20 ng/ml . Methods : A total of 133 patients with PSA < 20 ng/ml were prospect ively recruited . T2-weighted ( T2WI ) and diffusion-weighted ( DWI ) magnetic resonance images of the prostate were acquired before a 12-core transrectal prostate biopsy . Each patient 's peripheral zone was divided into six regions on the images ; each region corresponded to two of the 12 biopsy cores . T2WI , DWI , and T2WI + DWI scores were computed according to PI-RADS . The diagnostic accuracy of the PI-RADS score was evaluated using histopathology of prostate biopsies as the reference st and ard . Results : PCa was histologically diagnosed in 169 ( 21.2 % ) regions . Increased PI-RADS score correlated positively with increased cancer detection rate . The cancer detection rate for scores 1 to 5 was 2.8 % , 15.0 % , 34.6 % , 52.6 % , and 88.9 % , respectively , using T2WI and 12.0 % , 20.2 % , 48.0 % , 85.7 % , and 93.3 % , respectively , using DWI . For T2WI + DWI , the cancer detection rate was 1.5 % ( score 2 ) , 13.5 % ( scores 3–4 ) , 41.3 % ( scores 5–6 ) , 75.9 % ( scores 7–8 ) , and 92.3 % ( scores 9–10 ) . The area under the curve for cancer detection was 0.700 ( T2WI ) , 0.735 ( DWI ) and 0.749 ( T2WI + DWI ) . The sensitivity and specificity were 53.8 % and 89.2 % , respectively , when using scores 5–6 as the cutoff value for T2WI + DWI . Conclusions : The PI-RADS score correlates with the PCa detection rate in patients with PSA < 20 ng/ml . The summed score of T2WI + DWI has the highest accuracy in detection of PCa . However , the sensitivity should be further improved PURPOSE In patients with a negative prostate biopsy and persistent suspicion of prostate cancer , additional analyses such as the PCA3 score , PHI and multiparametric magnetic resonance imaging have been proposed to reduce the number of unnecessary repeat biopsies . In this study we evaluate the diagnostic accuracy of PCA3 , PHI , multiparametric magnetic resonance imaging and various combinations of these tests in the repeat biopsy setting . MATERIAL S AND METHODS A total of 170 patients with an initial negative prostate biopsy and persistent suspicion of prostate cancer were enrolled in this prospect i ve study . The patients underwent measurements of the total prostate specific antigen and free prostate specific antigen rate , along with PHI , PCA3 tests and multiparametric magnetic resonance imaging before st and ard repeat biopsy that was performed by urologists blinded to the multiparametric magnetic resonance imaging results . Multivariate logistic regression models with various combinations of PCA3 , PHI and multiparametric magnetic resonance imaging were used to identify the predictors of prostate cancer with repeat biopsy , and the performance of these models was compared using ROC curves , AUC analysis and decision curve analysis . RESULTS In the ROC analysis the most significant contribution was provided by multiparametric magnetic resonance imaging ( AUC 0.936 ) , which was greater than the contribution of the PHI+PCA3 model ( p < 0.001 ) . In the multivariate logistic regression analysis only multiparametric magnetic resonance imaging was a significant independent predictor of prostate cancer diagnosis with repeat biopsy ( p < 0.001 ) . The results of the decision curve analysis confirmed that the most significant improvement in the net benefit was provided by multiparametric magnetic resonance imaging . CONCLUSIONS Multiparametric magnetic resonance imaging provides high diagnostic accuracy in identifying patients with prostate cancer in the repeat biopsy setting compared with PCA3 and PHI PURPOSE To evaluate the role of a 3 T biparametric magnetic resonance imaging ( bpMRI ) , T2 -weighted imaging , and three separate diffusion-weighted imaging acquisitions combined with targeted biopsy ( TB ) for improving risk stratification of men with elevated prostate-specific antigen ( PSA ) . MATERIAL S AND METHODS Between March 2013 and February 2015 , 175 men with a clinical suspicion of prostate cancer ( PCa ) were offered bpMRI ( NCT01864135 ) based on a suspicion of PCa ( two repeated PSA measurements in the range 2.5 - 20.0 ng/ml and /or abnormal digital rectal examination ) . Men with an equivocal to high suspicion of PCa had two TBs of the dominant lesion using cognitive ultrasound guidance , followed by systematic biopsy ( SB ) . Men with a low to very low suspicion had only SB . In total , 161 ( 161/175 , 92 % ) prospect ively enrolled men completed the trial and were included in the final analyses . The primary endpoint of the trial was the cancer detection rate ( CDR ) of TB and SB . Clinical ly significant cancer ( SPCa ) was defined as Gleason score ≥3 + 4 . RESULTS TB compared with SB had higher CDR for SPCa ( 45 % , 72/161 vs. 39 % , 63/161 , respectively ; P > 0.05 ) and a lower CDR for Gleason score 3 + 3 ( 8 % , 15/161 vs. 16 % , 30/161 ; P < 0.05 ) . Restricting biopsy to men with equivocal to highly suspicious bpMRI findings would have result ed in a 24 % ( 38/161 ) reduction in the number of men undergoing biopsy , while missing 4 ( 2 % ) with SPCa . All anonymized data sets , including bpMRI reports and follow up information , are freely available on the trial server . CONCLUSION Prebiopsy bpMRI and TB in men with a clinical suspicion of PCa improved risk stratification . LEVEL OF EVIDENCE 1 Technical Efficacy : Stage 5 J. Magn . Reson . Imaging 2017;46:1089 - 1095 OBJECTIVE Multiparametric MRI ( mp-MRI ) of the prostate is increasingly being used for local staging and detection of recurrence of prostate cancer ( PCA ) . In patients with elevated prostate-specific antigen ( PSA ) , mp-MRI could provide information on the position of the cancer , allowing adjustments to be made to the needle depth and direction before repeat transrectal ultrasound (TRUS)-guided biopsy to ensure accurate sampling of lesions . The purpose of the prospect i ve study was to evaluate mp-MRI of the prostate in patients with PSA elevation before initial TRUS-guided biopsy . METHODS mp-MRI was performed in 94 patients using a 1.5-T scanner ( MAGNETOM Aera ( ® ) ; Siemens Healthcare , Erlangen , Germany ) and 16-channel phased-array body coil ( Siemens Healthcare ) . T2 weighted images ( T2WI ) , diffusion-weighted imaging ( DWI ) , dynamic contrast-enhanced ( DCE ) MRI and MR spectroscopy were obtained . TRUS-guided r and om biopsies and additional targeted biopsies of suspicious MRI areas were performed . RESULTS Additional targeted biopsies were obtained in 17 of 43 ( 40 % ) patients with PCA . 11 of 17 targeted biopsies contained PCA . 5 of 11 PCAs were diagnosed only by additional targeted biopsies . Sensitivity of mp-MRI in patients was 97.7 % and specificity was 11.8 % . mp-MRI was false negative in one patient . Sensitivity of mp-MRI in 207 lesions was 80.9 % and specificity was 44.7 % . In a logistic regression model , the apparent diffusion coefficient value was the only significant parameter to differentiate malignant and benign lesions . CONCLUSION mp-MRI should be performed in patients with PSA elevation before initial TRUS-guided biopsy to allow additional targeted biopsies from suspicious areas of MRI . We recommend mp-MRI with T2WI , DWI , DCE MRI and MR spectroscopy . DWI as the most reliable technique should be used in every mp-MRI . ADVANCES IN KNOWLEDGE DWI is the most reliable technique in mp-MRI of the prostate Purpose To vali date the dominant pulse sequence paradigm and limited role of dynamic contrast material -enhanced magnetic resonance ( MR ) imaging in the Prostate Imaging Reporting and Data System ( PI-RADS ) version 2 for prostate multiparametric MR imaging by using data from a multireader study . Material s and Methods This HIPAA-compliant retrospective interpretation of prospect ively acquired data was approved by the local ethics committee . Patients were treatment-naïve with endorectal coil 3-T multiparametric MR imaging . A total of 163 patients were evaluated , 110 with prostatectomy after multiparametric MR imaging and 53 with negative multiparametric MR imaging and systematic biopsy findings . Nine radiologists participated in this study and interpreted images in 58 patients , on average ( range , 56 - 60 patients ) . Lesions were detected with PI-RADS version 2 and were compared with whole-mount prostatectomy findings . Probability of cancer detection for overall , T2-weighted , and diffusion-weighted ( DW ) imaging PI-RADS scores was calculated in the peripheral zone ( PZ ) and transition zone ( TZ ) by using generalized estimating equations . To determine dominant pulse sequence and benefit of dynamic contrast-enhanced ( DCE ) imaging , odds ratios ( ORs ) were calculated as the ratio of odds of cancer of two consecutive scores by logistic regression . Results A total of 654 lesions ( 420 in the PZ ) were detected . The probability of cancer detection for PI-RADS category 2 , 3 , 4 , and 5 lesions was 15.7 % , 33.1 % , 70.5 % , and 90.7 % , respectively . DW imaging outperformed T2-weighted imaging in the PZ ( OR , 3.49 vs 2.45 ; P = .008 ) . T2-weighted imaging performed better but did not clearly outperform DW imaging in the TZ ( OR , 4.79 vs 3.77 ; P = .494 ) . Lesions classified as PI-RADS category 3 at DW MR imaging and as positive at DCE imaging in the PZ showed a higher probability of cancer detection than did DCE-negative PI-RADS category 3 lesions ( 67.8 % vs 40.0 % , P = .02 ) . The addition of DCE imaging to DW imaging in the PZ was beneficial ( OR , 2.0 ; P = .027 ) , with an increase in the probability of cancer detection of 15.7 % , 16.0 % , and 9.2 % for PI-RADS category 2 , 3 , and 4 lesions , respectively . Conclusion DW imaging outperforms T2-weighted imaging in the PZ ; T2-weighted imaging did not show a significant difference when compared with DW imaging in the TZ by PI-RADS version 2 criteria . The addition of DCE imaging to DW imaging scores in the PZ yields meaningful improvements in probability of cancer detection . © RSNA , 2017 An earlier incorrect version of this article appeared online . This article was corrected on July 27 , 2017 . Online supplemental material is available for this article Purpose To determine the diagnostic accuracy for clinical ly significant prostate cancer achieved with abbreviated biparametric prostate magnetic resonance ( MR ) imaging in comparison with full multiparametric contrast material -enhanced prostate MR imaging in men with elevated prostate-specific antigen ( PSA ) and negative transrectal ultrasonography (US)-guided biopsy findings ; to determine the significant cancer detection rate of biparametric versus full multiparametric contrast-enhanced MR imaging and between-reader agreement for interpretation of biparametric MR imaging . Material s and Methods In this institutional review board-approved retrospective review of prospect ively acquired data , men with PSA greater than or equal to 3 ng/mL after negative transrectal US-guided biopsy findings underwent state-of-the-art , full multiparametric contrast-enhanced MR imaging at 3.0-T including high-spatial-resolution structural imaging in several planes , diffusion-weighted imaging at 0 , 800 , 1000 , and 1400 mm2/sec , and dynamic contrast-enhanced MR imaging , obtained without endorectal coil within 34 minutes 19 seconds . One of four radiologists with different levels of expertise ( 1 - 9 years ) first review ed only a fraction of the full multiparametric contrast-enhanced MR images , consisting of single-plane ( axial ) structural imaging ( T2-weighted turbo spin-echo and diffusion-weighted imaging ) , acquired within 8 minutes 45 seconds ( referred to as biparametric MR imaging ) , and established a diagnosis according to the Prostate Imaging Reporting and Data System ( PI-RADS ) version 2 ; only thereafter , the remaining full multiparametric contrast-enhanced MR images were read . Men with PI-RADS categories 3 - 5 underwent MR-guided targeted biopsy . Men with PI-RADS categories 1 - 2 remained in urologic follow-up for at least 2 years , with rebiopsy ( transrectal US-guided or transperineal saturation ) where appropriate . McNemar test was used to compare diagnostic accuracies . To investigate between-reader agreement , biparametric MR images of 100 patients were read independently by all three radiologists . Results A total of 542 men , aged 64.8 years ± 8.2 ( median PSA , 7 ng/mL ) , were included . Biparametric MR imaging helped detect clinical ly significant prostate cancer in 138 men . Full multiparametric contrast-enhanced MR imaging allowed detection of one additional clinical ly significant prostate cancer ( a stage pT2a , intermediate-risk cancer with a Gleason score of 3 + 4 ) and caused 11 additional false-positive diagnoses . Diagnostic accuracy for detection of clinical ly significant cancer of biparametric MR imaging ( 89.1 % , 483 of 542 ) was similar to that of full multiparametric contrast-enhanced MR imaging ( 87.2 % , 473 of 542 ) . Between-reader agreement of biparametric MR imaging interpretation was substantial ( κ = 0.81 ) . Conclusion Biparametric MR imaging allows detection of clinical ly significant prostate cancer missed by transrectal US-guided biopsy . Biparametric prostate MR imaging takes less than 9 minutes examination time , works without contrast agent injection , and offers a diagnostic accuracy and cancer detection rate that are equivalent to those of conventional full multiparametric contrast-enhanced MR imaging protocol s. © RSNA , 2017 PURPOSE Multiparametric magnetic resonance imaging and magnetic resonance imaging targeted biopsy may improve the detection of clinical ly significant prostate cancer . However , st and ardized prospect i ve evaluation is limited . MATERIAL S AND METHODS A total of 294 consecutive men with suspicion of prostate cancer ( 186 primary , 108 repeat biopsies ) enrolled in 2013 underwent 3 T multiparametric magnetic resonance imaging ( T2-weighted , diffusion weighted , dynamic contrast enhanced ) without endorectal coil and systematic transperineal cores ( median 24 ) independently of magnetic resonance imaging suspicion and magnetic resonance imaging targeted cores with software registration ( median 4 ) . The highest Gleason score from each biopsy method was compared . McNemar 's tests were used to evaluate detection rates . Predictors of Gleason score 7 or greater disease were assessed using logistic regression . RESULTS Overall 150 cancers and 86 Gleason score 7 or greater cancers were diagnosed . Systematic , transperineal biopsy missed 18 Gleason score 7 or greater tumors ( 20.9 % ) while targeted biopsy did not detect 11 ( 12.8 % ) . Targeted biopsy of PI-RADS 2 - 5 alone overlooked 43.8 % of Gleason score 6 tumors . McNemar 's tests for detection of Gleason score 7 or greater cancers in both modalities were not statistically significant but showed a trend of superiority for targeted primary biopsies ( p=0.08 ) . Sampling efficiency was in favor of magnetic resonance imaging targeted prostate biopsy with 46.0 % of targeted biopsy vs 7.5 % of systematic , transperineal biopsy cores detecting Gleason score 7 or greater cancers . To diagnose 1 Gleason score 7 or greater cancer , 3.4 targeted and 7.4 systematic biopsies were needed . Limiting biopsy to men with PI-RADS 3 - 5 would have missed 17 Gleason score 7 or greater tumors ( 19.8 % ) , demonstrating limited magnetic resonance imaging sensitivity . PI-RADS scores , digital rectal examination findings and prostate specific antigen greater than 20 ng/ml were predictors of Gleason score 7 or greater disease . CONCLUSIONS Compared to systematic , transperineal biopsy as a reference test , magnetic resonance imaging targeted biopsy alone detected as many Gleason score 7 or greater tumors while simultaneously mitigating the detection of lower grade disease . The gold st and ard for cancer detection in primary biopsy is a combination of systematic and targeted cores Aim . To evaluate diffusion weighted image-MRI ( DWI ) as a single diagnostic noninvasive MRI technique for prostate cancer ( PCa ) diagnosis . Material and Methods . A prospect i ve study was conducted between July 2008 and July 2009 . C and i date s patients were equal or more than 40 years old , with suspicious digital rectal examination ( more than clinical T2 ) or PSA > 4 ng/mL. Informed consent was signed . DWI-MRI was performed at 1.5 T with a body coil combined with a spine coil in consecutive 100 cases . The histopathology of biopsies has been used as reference st and ard . Two examiners were evaluating MRI and TRUS , both of them were blinded regarding pathological findings . Accuracy , specificity , and sensitivity were statistically analyzed . Results . Based on pathological diagnosis : group A ( cancerous ) ; 75 cases and group B ( non-cancerous ) ; 25 cases . Mean age was 65.3 and 62.8 years in groups A and B , respectively . Mean PSA was 30.7 and 9.2 ng/mL in groups A and B , respectively . Sensitivity of DWI was 58.3 % while specificity was 83.8 % . Accuracy of lesion detection was 52.4–77.8 % ( P < 0.05 ) . Moreover , DWI at ADC value 1.2 × 10−3 mL/sec could determine 82.4 % of true positive cases ( P < 0.05 ) . ADC values were lower with Gleason score ≥7 ( P < 0.05 ) . Conclusion . DWI could represent a non invasive single diagnostic tool not only in detection and localization but also in prediction of Gleason score whenever DWI is used prior to invasive TRUS biopsy . Furthermore , targeted single biopsy could be planned after DWI to minimize patient morbidity by invasive techniques PURPOSE Multiparametric magnetic resonance imaging appears to improve prostate cancer detection but prospect i ve studies are lacking . We determined the accuracy of multiparametric magnetic resonance imaging for detecting significant prostate cancer before diagnostic biopsy in men with abnormal prostate specific antigen/digital rectal examination . MATERIAL S AND METHODS In this single center , prospect i ve study men older than 40 years with abnormal prostate specific antigen/digital rectal examination and no previous multiparametric magnetic resonance imaging underwent T2-weighted , diffusion-weighted and dynamic contrast enhanced imaging without an endorectal coil . Imaging was allocated alternately to 1.5/3.0 Tesla . Imaging was double reported independently using PI-RADS ( Prostate Imaging Reporting and Data System ) by specialist radiologists . Transperineal grid directed 30-core biopsy was performed with additional magnetic resonance imaging directed cores for regions of interest outside template locations . Four significant cancer definitions were tested . Chi-square and logistic regression analysis was done . Men undergoing prostatectomy were analyzed . RESULTS Of the 165 men who enrolled in the study 150 were analyzed . Median age was 62.4 years , median prostate specific antigen was 5.6 ng/ml , 29 % of patients had an abnormal digital rectal examination and 88 % underwent initial biopsy . Multiparametric magnetic resonance imaging was positive ( PI-RADS 3 to 5 ) in 66 % of patients , 61 % had prostate cancer and 30 % to 41 % had significant prostate cancer ( definitions 1 to 4 ) . For significant cancer sensitivity was 93 % to 96 % , specificity was 47 % to 53 % , and negative and positive predictive values were 92 % to 96 % and 43 % to 57 % , respectively ( definitions 1 to 4 ) . Radical prostatectomy results in 48 men were similar . Aggregate PI-RADS ( 4 to 20 ) performed similarly to overall PI-RADS ( 1 to 5 ) . Negative and positive predictive values ( 100 % and 71 % , respectively ) were similar in men at higher risk , defined as prostate specific antigen greater than 10 ng/ml with abnormal digital rectal examination . On multivariate analysis PI-RADS score was associated with significant prostate cancer ( p < 0.001 ) but magnet strength was not . Adding PI-RADS to the multivariate model improved the AUC from 0.810 to 0.913 ( 95 % CI 0.038 - 0.166 , p = 0.002 ) . Radiologist agreement was substantial ( weighted κ = 0.626 ) . CONCLUSIONS Multiparametric magnetic resonance imaging reported by expert radiologists achieved an excellent negative predictive value and a moderate positive predictive value for significant prostate cancer at 1.5 and 3.0 Tesla BACKGROUND An approach based on multiparametric magnetic resonance imaging ( mpMRI ) might increase the detection rate ( DR ) of clinical ly significant prostate cancer ( csPCa ) . OBJECTIVE To compare an mpMRI-based pathway with the st and ard approach for the detection of prostate cancer ( PCa ) and csPCa . DESIGN , SETTING , AND PARTICIPANTS Between November 2014 and April 2016 , 212 biopsy-naïve patients with suspected PCa ( prostate specific antigen level ≤15 ng/ml and negative digital rectal examination results ) were included in this r and omized clinical trial . Patients were r and omized into a prebiopsy mpMRI group ( arm A , n=107 ) or a st and ard biopsy ( SB ) group ( arm B , n=105 ) . INTERVENTION In arm A , patients with mpMRI evidence of lesions suspected for PCa underwent mpMRI/transrectal ultrasound fusion software-guided targeted biopsy ( TB ) ( n=81 ) . The remaining patients in arm A ( n=26 ) with negative mpMRI results and patients in arm B underwent 12-core SB . OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS The primary end point was comparison of the DR of PCa and csPCa between the two arms of the study ; the secondary end point was comparison of the DR between TB and SB . RESULTS AND LIMITATIONS The overall DRs were higher in arm A versus arm B for PCa ( 50.5 % vs 29.5 % , respectively ; p=0.002 ) and csPCa ( 43.9 % vs 18.1 % , respectively ; p<0.001 ) . Concerning the biopsy approach , that is , TB in arm A , SB in arm A , and SB in arm B , the overall DRs were significantly different for PCa ( 60.5 % vs 19.2 % vs 29.5 % , respectively ; p<0.001 ) and for csPCa ( 56.8 % vs 3.8 % vs 18.1 % , respectively ; p<0.001 ) . The reproducibility of the study could have been affected by the single-center nature . CONCLUSIONS A diagnostic pathway based on mpMRI had a higher DR than the st and ard pathway in both PCa and csPCa . PATIENT SUMMARY In this r and omized trial , a pathway for the diagnosis of prostate cancer based on multiparametric magnetic resonance imaging ( mpMRI ) was compared with the st and ard pathway based on r and om biopsy . The mpMRI-based pathway had better performance than the st and ard pathway Purpose : This study aim ed to prospect ively analyze the role of magnetic resonance spectroscopy imaging ( MRSI ) and dynamic-contrast enhancement magnetic resonance ( DCEMR ) in the detection of prostate tumor foci in patients with persistently elevated prostate-specific antigen levels ( in the range of ≥4 ng/mL to < 10 ng/mL ) and prior negative r and om trans-rectal ultrasound (TRUS)-guided biopsy . Experimental Design : This was a prospect i ve r and omized single-center study . One hundred and eighty eligible cases were included in the study . Patients in group A were su bmi tted to a second r and om prostate biopsy , whereas patients in group B were su bmi tted to a 1H-MRSI-DCEMR examination and sample s targeted on suspicious areas were associated to the r and om biopsy . Results : At the second biopsy , a prostate adenocarcinoma histologic diagnosis was found in 22 of 90 cases ( 24.4 % ) in group A and in 41 of 90 cases ( 45.5 % ) in group B ( P = 0.01 ) . On a patient-by-patient basis , MRSI had 92.3 % sensitivity , 88.2 % specificity , 85.7 % positive predictive value ( PPV ) , 93.7 % negative predictive value ( NPV ) , and 90 % accuracy ; DCEMR had 84.6 % sensitivity , 82.3 % specificity , 78.5 % PPV , 87.5 % NPV , and 83.3 % accuracy ; and the association MRSI plus DCEMR had 92.6 % sensitivity , 88.8 % specificity , 88.7 % PPV , 92.7 % NPV , and 90.7 % accuracy , for predicting prostate cancer detection . Conclusions : The combination of MRSI and DCEMR showed the potential to guide biopsy to cancer foci in patients with previously negative TRUS biopsy . To avoid a potential bias , represented from having taken more sample s in group B ( mean of cores , 12.17 ) than in group A ( 10 cores ) , in the future a MRSI/DCEMR directed biopsy could be prospect ively compared with a saturation biopsy procedure . Clin Cancer Res ; 16(6 ) ; Background and aim Multiparametric-magnetic resonance imaging ( mp-MRI ) is the main imaging modality used for prostate cancer detection . The aim of this study is to evaluate the diagnostic performance of mp-MRI at 1.5-Tesla ( 1.5-T ) for the detection of clinical ly significant prostate cancer . Methods In this ethical board approved prospect i ve study , 39 patients with suspected prostate cancer were included . Patients with a history of positive prostate biopsy and patients treated for prostate cancer were excluded . All patients were examined at 1.5-T MRI , before st and ard transrectal ultrasonography – guided biopsy . Results The overall sensitivity , specificity , positive predictive value and negative predictive value for mp-MRI were 100 % , 73.68 % , 80 % and 100 % , respectively . Conclusion Our results showed that 1.5 T mp-MRI has a high sensitivity for detection of clinical ly significant prostate cancer and high negative predictive value in order to rule out significant disease OBJECTIVE To overcome the well-known prostate-specific antigen limits , several new biomarkers have been proposed . Since its introduction in clinical practice , the urinary prostate cancer gene 3 ( PCA3 ) assay has shown promising results for prostate cancer ( PC ) detection . Furthermore , multiparametric magnetic resonance imaging ( mMRI ) has the ability to better describe several aspects of PC . METHODS A prospect i ve study of 171 patients with negative prostate biopsy findings and a persistent high prostate-specific antigen level was conducted to assess the role of mMRI and PCA3 in identifying PC . All patients underwent the PCA3 test and mMRI before a second transrectal ultrasound-guided prostate biopsy . The accuracy and reliability of PCA3 ( 3 different cutoff points ) and mMRI were evaluated . Four multivariate logistic regression models were analyzed , in terms of discrimination and the cost benefit , to assess the clinical role of PCA3 and mMRI in predicting the biopsy outcome . A decision curve analysis was also plotted . RESULTS Repeated transrectal ultrasound-guided biopsy identified 68 new cases ( 41.7 % ) of PC . The sensitivity and specificity of the PCA3 test and mMRI was 68 % and 49 % and 74 % and 90 % , respectively . Evaluating the regression models , the best discrimination ( area under the curve 0.808 ) was obtained using the full model ( base clinical model plus mMRI and PCA3 ) . The decision curve analysis , to evaluate the cost/benefit ratio , showed good performance in predicting PC with the model that included mMRI and PCA3 . CONCLUSION mMRI increased the accuracy and sensitivity of the PCA3 test , and the use of the full model significantly improved the cost/benefit ratio , avoiding unnecessary biopsies OBJECTIVES To assess whether the proportion of men with clinical ly significant prostate cancer ( PCa ) is higher among men r and omized to multiparametric magnetic resonance imaging (mp-MRI)/biopsy vs. those r and omized to transrectal ultrasound (TRUS)-guided biopsy . METHODS In total , 1,140 patients with symptoms highly suggestive of PCa were enrolled and divided in 2 groups of 570 patients to follow 2 different diagnostic algorithms . Group A underwent a TRUS-guided r and om biopsy . Group B underwent an mp-MRI and a TRUS-guided targeted+r and om biopsy . The accuracy of mp-MRI in the diagnosis of PCa was calculated using prostatectomy as the st and ard of reference . RESULTS In group A , PCa was detected in 215 patients . The remaining 355 patients underwent an mp-MRI : the findings were positive in 208 and unremarkable in 147 patients . After the second r and om+targeted biopsy , PCa was detected in 186 of the 208 patients . In group B , 440 patients had positive findings on mp-MRI , and PCa was detected in 417 at first biopsy ; 130 group B patients had unremarkable findings on both mp-MRI and biopsy . In the 130 group B patients with unremarkable findings on mp-MRI and biopsy , a PCa Gleason score of 6 or precancerous lesions were detected after saturation biopsy . mp-MRI showed an accuracy of 97 % for the diagnosis of PCa . CONCLUSIONS The proportion of men with clinical ly significant PCa is higher among those r and omized to mp-MRI/biopsy vs. those r and omized to TRUS-guided biopsy ; moreover , mp-MRI is a very reliable tool to identify patients to schedule in active surveillance INTRODUCTION Prebiopsy multiparametric magnetic resonance imaging ( MRI ) is increasingly used in clinical practice to detect clinical ly significant prostate cancer , although its role is controversial . We audited the accuracy of prebiopsy MRI for men clinical ly suspected to have prostate cancer who underwent initial transrectal ultrasound ( TRUS ) biopsy at our institution . PATIENTS AND METHODS All patients who had a prebiopsy prostate MRI and initial TRUS prostate biopsy from January 1 , 2013 to December 31 , 2013 were included in the study . Prostate MRI was performed using a 1.5-T machine with T2 and diffusion weighted imaging axial phase . TRUS prostate biopsy was performed using a monoplane ultrasound machine . Systematic 12-core prostate biopsies were taken with a Tru-Cut biopsy needle from the apex , middle , and base of the left and right lobe . RESULTS One hundred seventy-three patients met the inclusion criteria ; 128 ( 74.4 % ) patients had a lesion detected on MRI and 114 ( 66.3 % ) patients had a positive biopsy . The sensitivity of MRI for significant prostate cancer on TRUS biopsy of the prostate was 83.5 % , specificity was 35.2 % , positive predictive value was 55 % , and negative predictive value was 68.9 % . A positive MRI scan was significantly associated with significant prostate cancer diagnosis , and higher National Comprehensive Cancer Network ( NCCN ) risk classification ( P ≤ .001 ) . MRI detected 62 of 63 NCCN high-risk and 18 of 18 Gleason score 8 to 10 cases . CONCLUSION The sensitivity and specificity of MRI appears insufficient to avoid TRUS biopsy in all men clinical ly suspected to have prostate cancer . St and ardized MRI reporting and robust prospect i ve studies are needed to define the role of prebiopsy MRI in this setting . For patients at risk of complications from biopsy , a negative MRI scan might be used to exclude high-risk disease The purpose of this study is to report our method in detecting prostate cancer ( PCa ) using an 18-core transrectal ultrasound ( TRUS ) prostate biopsy ( PB ) schema , in combination with additional targeted cores from suspicious images in conventional ( e-cMRI ) and functional ( e-fMRI ) endorectal magnetic resonance imaging ( e-MRI ) of the prostate . From 2004 to 2008 , 260 consecutive patients with a clinical suspicion of PCa underwent PB and were prospect ively studied . e-cMRI and e-fMRI was performed in all patients before PB . The patients were divided into two groups ( A and B ) according to the results of their radiological findings ( group A = suspicious findings , group B = non-suspicious findings ) . After the images were processed , an 18-core TRUS-guided PB was performed . When a patient exhibited a suspicious site on e-cMRI and e-fMRI images , three additional targeted PBs were obtained from that site . In group A , 17.5 % of PCa was detected by the 18-core PB and 56.5 % of PCa was detected by the targeted cores . The overall PCa detection rate ( 18+targeted cores ) was 73.9 % . The overall specificity was 73.9 % . In group B , overall false-positive detection rate reached 19.2 % , with the overall sensitivity being 80.8 % . The method described above is not only practical but also a promising modality in PCa detection . As seen , PCa was optimally detected when combining the 18-core and targeted-core PB schema together . Non-suspicious images do not rule out the probability of PCa , thus justifying a PB in these patients as well PURPOSE Diagnosis and precise risk stratification of prostate cancer is essential for individualized treatment decisions . Magnetic resonance imaging/transrectal ultrasound fusion has shown encouraging results for detecting clinical ly significant prostate cancer . We critically evaluated magnetic resonance imaging targeted , transrectal ultrasound guided transperineal fusion biopsy in routine clinical practice . MATERIAL S AND METHODS Included in this prospect i ve study were 347 consecutive patients with findings suspicious for prostate cancer . Median age was 65 years ( range 42 to 84 ) and mean prostate specific antigen was 9.85 ng/ml ( range 0.5 to 104 ) . Of the men 49 % previously underwent transrectal ultrasound guided biopsies , which were negative , and 51 % underwent primary biopsy . In all patients 3 Tesla multiparametric magnetic resonance imaging was done . Systematic stereotactic prostate biopsies plus magnetic resonance imaging targeted , transrectal ultrasound guided biopsies were performed in those with abnormalities on magnetic resonance imaging . Imaging data and biopsy results were analyzed . A self- design ed question naire was sent to all men on further clinical history and biopsy adverse effects . RESULTS Of 347 patients biopsy sample s of 200 ( 58 % ) showed prostate cancer and 73.5 % of biopsy proven prostate cancer were clinical ly relevant according to National Comprehensive Cancer Network ( NCCN ) criteria . On multiparametric magnetic resonance imaging 104 men had findings highly suspicious for prostate cancer . The tumor detection rate was 82.6 % ( 86 of 104 men ) with a Gleason score of 7 or greater in 72 % . Overall targeted cores detected significantly more cancer than systematic biopsies ( 30 % vs 8.2 % ) . Of 94 patients without cancer suspicious lesions on magnetic resonance imaging 11 ( 11.7 % ) were diagnosed with intermediate risk disease . Regarding adverse effects , 152 of 300 patients ( 50.6 % ) reported mild hematuria , 26 % had temporary erectile dysfunction and 2.6 % needed short-term catheterization after biopsy . Nonseptic febrile urinary tract infections developed in 3 patients ( 1 % ) . CONCLUSIONS Magnetic resonance imaging targeted , transrectal ultrasound guided transperineal fusion biopsy provides high detection of clinical ly significant tumors . Since multiparametric magnetic resonance imaging still has some limitations , systematic biopsies should currently not be omitted . The morbidity of the transperineal saturation approach is reasonable and mainly self-limiting BACKGROUND The current diagnosis of prostate cancer ( PCa ) uses transrectal ultrasound-guided biopsy ( TRUSGB ) . TRUSGB leads to sampling errors causing delayed diagnosis , overdetection of indolent PCa , and misclassification . Advances in multiparametric magnetic resonance imaging ( mpMRI ) suggest that imaging and selective magnetic resonance (MR)-guided biopsy ( MRGB ) may be superior to TRUSGB . OBJECTIVE To compare the diagnostic efficacy of the magnetic resonance imaging ( MRI ) pathway with TRUSGB . DESIGN , SETTING , AND PARTICIPANTS A total of 223 consecutive biopsy-naive men referred to a urologist with elevated prostate-specific antigen participated in a single-institution , prospect i ve , investigator-blinded , diagnostic study from July 2012 through January 2013 . INTERVENTION All participants had mpMRI and TRUSGB . Men with equivocal or suspicious lesions on mpMRI also underwent MRGB . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary outcome was PCa detection . Secondary outcomes were histopathologic details of biopsy and radical prostatectomy specimens , adverse events , and MRI reader performance . Sensitivity , specificity , negative predictive values ( NPVs ) , and positive predictive values were estimated and basic statistics presented by number ( percentage ) or median ( interquartile range ) . RESULTS AND LIMITATIONS Of 223 men , 142 ( 63.7 % ) had PCa . TRUSGB detected 126 cases of PCa in 223 men ( 56.5 % ) including 47 ( 37.3 % ) classed as low risk . MRGB detected 99 cases of PCa in 142 men ( 69.7 % ) with equivocal or suspicious mpMRI , of which 6 ( 6.1 % ) were low risk . The MRGB pathway reduced the need for biopsy by 51 % , decreased the diagnosis of low-risk PCa by 89.4 % , and increased the detection of intermediate/high-risk PCa by 17.7 % . The estimated NPVs of TRUSGB and MRGB for intermediate/high-risk disease were 71.9 % and 96.9 % , respectively . The main limitation is the lack of long follow-up . CONCLUSIONS We found that mpMRI/MRGB reduces the detection of low-risk PCa and reduces the number of men requiring biopsy while improving the overall rate of detection of intermediate/high-risk PCa . PATIENT SUMMARY We compared the results of st and ard prostate biopsies with a magnetic resonance ( MR ) image-based targeted biopsy diagnostic pathway in men with elevated prostate-specific antigen . Our results suggest patient benefits of the MR pathway . Follow-up of negative investigations is required BACKGROUND AND OBJECTIVE Publication bias and other sample size effects are issues for meta-analyses of test accuracy , as for r and omized trials . We investigate limitations of st and ard funnel plots and tests when applied to meta-analyses of test accuracy and look for improved methods . METHODS Type I and type II error rates for existing and alternative tests of sample size effects were estimated and compared in simulated meta-analyses of test accuracy . RESULTS Type I error rates for the Begg , Egger , and Macaskill tests are inflated for typical diagnostic odds ratios ( DOR ) , when disease prevalence differs from 50 % and when thresholds favor sensitivity over specificity or vice versa . Regression and correlation tests based on functions of effective sample size are valid , if occasionally conservative , tests for sample size effects . Empirical evidence suggests that they have adequate power to be useful tests . When DORs are heterogeneous , however , all tests of funnel plot asymmetry have low power . CONCLUSION Existing tests that use st and ard errors of odds ratios are likely to be seriously misleading if applied to meta-analyses of test accuracy . The effective sample size funnel plot and associated regression test of asymmetry should be used to detect publication bias and other sample size related effects BACKGROUND Wide variations in acquisition protocol s and the lack of robust diagnostic criteria make magnetic resonance imaging ( MRI ) detection of prostate cancer ( PCa ) one of the most challenging fields in radiology and urology . OBJECTIVE To vali date the recently proposed European Society of Urogenital Radiology ( ESUR ) scoring system for multiparametric MRI ( mpMRI ) of the prostate . DESIGN , SETTING , AND PARTICIPANTS An institutional review board-approved multicentric prospect i ve study ; 129 consecutive patients ( 1514 cores ) referred for mpMRI after at least one set of negative biopsies . INTERVENTION Transfer of mpMRI-suspicious areas on three-dimensional ( 3D ) transrectal ultrasound images by 3D elastic surface registration ; r and om systematic and targeted cores followed by core-by-core analysis of pathology and mpMRI characteristics of the core locations . The ESUR scores were assigned after the procedure on annotated Digital Imaging and Communications in Medicine archives . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Relationships between ESUR scores and biopsy results were assessed by the Mann-Whitney U test . The Yates correction and Pearson χ(2 ) tests evaluated the association between categorical variables . A teaching set was r and omly drawn to construct the receiver operating characteristic curve of the ESUR score sum ( ESUR-S ) . The threshold to recommend biopsy was obtained from the Youden J statistics and tested in the remaining validation set in terms of sensitivity , specificity , positive predictive value , negative predictive value , and accuracy . RESULTS AND LIMITATIONS Higher T2-weighted , dynamic weighted imaging and dynamic contrast-enhanced ESUR scores were observed in areas yielding cancer-positive cores . The proportion of positive cores increased with the ESUR-S aggregated in five increments ( ESUR-S 3 - 5 : 2.9 % ; ESUR-S 6 - 8 : 11.1 % ; ESUR-S 9 - 10 : 38.2 % ; ESUR-S 11 - 12 : 63.4 % ; and ESUR-S 13 - 15 : 83.3 % ; p<0.0001 ) . A threshold of ESUR-S ≥ 9 exhibited the following characteristics : sensitivity : 73.5 % ; specificity : 81.5 % ; positive predictive value : 38.2 % ; negative predictive value : 95.2 % ; and accuracy : 80.4 % . Although the study was not design ed to compare repeat biopsy strategies , more targeted cores than r and om systematic cores were found to be positive for cancer ( 36.3 % compared with 4.9 % , p<0.00001 ) . CONCLUSIONS In the challenging situation of repeat biopsies , the ESUR scoring system was shown to provide clinical ly relevant stratification of the risk of showing PCa in a given location AIM To assess the role of multiparametric 3 T magnetic resonance ( 3TMRI ) of the prostate in detection of the prostatic carcinoma in a male population with elevated prostatic-specific antigen ( PSA ) and to compare the results with those of transrectal biopsies . MATERIAL S AND METHODS A prospect ively collected cohort of 191 men underwent 3 T MRI before transrectal biopsy . The evaluation consisted of the assessment of T2-weighted images , diffusion-weighted images , MR spectroscopy and the pharmacokinetic evaluation of the data obtained during the dynamic post-contrast T1 imaging . The assessment included the calculation of the blood volume and transfer constant evaluations . The diagnosis of prostate carcinoma was based on a minimum of three positive signs obtained from MR studies --hypointensive T2 lesion , diffusion restriction , elevated choline/creatine peak in spectrum and malignant type of saturation by contrast agents . All biopsies were evaluated by a specialist in uropathology . RESULTS 164 patients underwent biopsy , in 27 the biopsy was omitted due to a lack or low probability of carcinoma : Overall , 84 carcinomas were found . Based on the comparison of biopsy results , 3 T MRI reached a sensitivity of 97.6 % , specificity of 85.0 % , positive predictive value of 74.6 % and negative predictive value of 96,3 % respectively . There were only three false negative findings . In three patients with very suspicious MRI findings and PSA levels over 30 ng/ml , the biopsy did not confirm carcinoma , even though it was highly suspected . CONCLUSION The implementation of 3 T MRI in routine assessment of patients with elevated PSA should reduce the number of biopsies performed and improve the number of tumors detected due to better targeted biopsies OBJECTIVES To intraindividually compare image quality and diagnostic performance of multiparametric MRI ( mpMRI ) at 3 T for the detection of prostate cancer ( PCa ) using a pelvic phased-array coil ( PAC ) and a combined endorectal and pelvic phased-array coil ( ERC-PAC ) . METHODS Forty-five patients were prospect ively included and received mpMRI of the prostate using a PAC and an ERC-PAC during one imaging session . Two radiologists evaluated image quality and the most suspicious lesion according to the PI-RADS scoring system . Results of MRI-TRUS-fusion biopsy of the prostate served as reference st and ard . Patient comfort and acceptance were assessed using a st and ardized question naire . RESULTS Overall image quality for T2WI was rated significantly better with an ERC-PAC compared to a PAC ( p=0.0038 ) . The weighted kappa for PI-RADS scores for T2WI and DWI with a PAC and an ERC-PAC was 0.70 and 0.73 , respectively . For a PI-RADS sum score including T2WI and DWI the area under the curve with a PAC and an ERC-PAC were 0.95 - 0.99 and 0.93 - 0.97 , respectively ( p=0.1395 ) . CONCLUSION For T2WI and DWI performed at 3 T index PCa lesion identification and evaluation did not differ significantly with both coil setups . Patients preferred MRI without an ERC . Therefore , the use of an ERC may be omitted in a prostate cancer detection setting Can focal therapy successfully control prostate cancer ? Also , if so , which patients should be considered eligible ? With limited data available from relatively few patients , these questions are difficult to answer . At this writing , the most likely c and i date s for focal therapy are patients with low-risk , small-volume tumors , located in 1 region or sector of the prostate , who would benefit from early intervention . The difficulty lies in reliably identifying these men . The larger number of cores obtained in each needle biopsy session has increased both the detection of prostate cancer and the potential risk of overtreating many patients whose cancers pose very little risk to life or health . Urologists typically perform at least a 12-core template biopsy . Although the debate continues about the optimal template , laterally and peripherally directed biopsies have been shown to improve the diagnostic yield . However , as many as 25 % of tumors arise anteriorly and can be missed with peripherally directed techniques . Prostate cancer tends to be multifocal , even in its earliest stages . However , the secondary cancers are usually smaller and less aggressive than the index cancer . They appear similar to the incidental cancers found in cystoprostatectomy specimens and appear to have little effect on prognosis in surgical series . When a single focus of cancer is found in 1 core , physicians rightly suspect that more foci of cancer are present in the prostate . Assessing the risk in these patients is challenging when determined by the biopsy data alone . To predict the presence of a very low-risk or " indolent " cancer , nomograms have been developed to incorporate clinical stage , Gleason grade , prostate-specific antigen levels , and prostate volume , along with the quantitative analysis of the biopsy results . Transperineal " mapping " or " saturation " biopsies have been advocated to detect cancers missed or underestimated by previous transrectal biopsies . This approach could provide the accurate staging , grading , and tumor localization needed for a focal therapy program . Nevertheless , for men with minimal cancer who are amenable to active surveillance or focal therapy , consensus about the most accurate biopsy strategy has not yet been reached . Imaging , particularly magnetic resonance imaging and magnetic resonance spectroscopic imaging , has been used to assess men with early-stage prostate cancer . Large-volume cancers can be seen reasonably well , but small lesions have been difficult to detect reliably or measure accurately . Factors such as voxel resolution , organ movement , biopsy artifact , and benign changes have limited the consistent estimation of the quantitative tumor volume . Nevertheless , magnetic resonance imaging and magnetic resonance spectroscopic imaging can aid in evaluating patients with prostate cancer being considered for focal therapy by providing additional evidence that the patient does not harbor an otherwise undetected high-risk , aggressive cancer . In some cases , imaging can usefully identify the location of even a limited-sized index cancer . When imaging findings are substantiated by mapping biopsy results , confidence in the accurate characterization of the cancer is enhanced . Correlating the imaging results with tissue changes during and after treatment can be of use in monitoring the ablative effects in the prostate and in assessing for tumor recurrence . More work is necessary before staging studies can uniformly characterize a prostate cancer before therapy , much less reliably identify and locate small-volume cancer within the prostate . However , exploring the role of focal ablation as a therapeutic option for selected men with low-risk , clinical ly localized , prostate cancer need not await the emergence of perfectly accurate staging studies , any more than the application of radical surgery or radiotherapy have . Modern biopsy strategies , combined with optimal imaging and nomograms to estimate the pathologic stage and risk , taken together , provide a sound basis for the selection of appropriate patients for entry into prospect i ve clinical trials of focal therapy PURPOSE To compare the performance of pelvic phased-array ( PPA ) coils and integrated endorectal PPA coils in evaluation of local extent of prostate cancer . MATERIAL S AND METHODS Seventy-one men underwent magnetic resonance ( MR ) imaging within 3 weeks of radical prostatectomy . MR findings of tumor , extracapsular extension , seminal vesicle invasion , nodal involvement , and stage were compared with step-sectioned ( 3 - 4-mm intervals ) whole-mounted pathologic specimens . Prospect i ve consensus versus single-reader interpretation ( kappa statistics ) and PPA versus integrated endorectal PPA coils ( McNemar test ) were compared , and a rating scale of 1 - 6 was developed for analysis of receiver operating characteristics . Statistical significance was calculated at delta = .05 . RESULTS Comparison between consensus and single-reader image interpretation showed positive but poor agreement ( kappa = .38 ) and no statistical significance . Staging accuracy was better ( difference approached significance ) for integrated endorectal PPA coils ( 77 % ) than for PPA coils ( 68 % ) . CONCLUSION The integrated endorectal PPA coil is better for evaluation of local prostatic cancer than is the PPA coil PURPOSE We evaluated the usefulness of pre-biopsy multiparametric magnetic resonance imaging and clinical variables to decrease initial prostate biopsies . MATERIAL S AND METHODS We prospect ively evaluated 351 consecutive men with prostate specific antigen between 2.5 and 20 ng/ml , and /or digital rectal examination suspicious for clinical ly localized disease . All men underwent pre-biopsy multiparametric magnetic resonance imaging and initial 14 to 29-core biopsy , including anterior sampling . Three definitions of significant cancer were defined based on Gleason score and cancer volume ( percent positive core and /or maximum cancer length ) . The overall cohort was divided into men at low risk-prostate specific antigen less than 10 ng/ml and normal digital rectal examination , and high risk-prostate specific antigen 10 ng/ml or greater and /or abnormal digital rectal examination . We evaluated the frequency of significant cancer according to magnetic resonance imaging and risk categories . Clinical variables as significant cancer predictors were analyzed using logistic regression . The sensitivity , specificity , and positive and negative predictive values of magnetic resonance imaging were calculated with or without clinical variables for significant cancer . RESULTS The frequency of significant cancer in men with negative vs positive magnetic resonance imaging was 9 % to 13 % vs 43 % to 50 % in the low risk group and 47 % to 51 % vs 68 % to 71 % in the high risk group . In men at low risk with negative magnetic resonance imaging prostate volume was the only significant predictor of significant cancer . In the low risk group the negative predictive value for significant cancer of a combination of positive magnetic resonance imaging and lower prostate volume ( less than 33 ml ) was 93.7 % to 97.5 % . CONCLUSIONS Pre-biopsy multiparametric magnetic resonance imaging along with prostate volume decreases the number of initial prostate biopsies by discriminating between significant cancer and other cancer in men with prostate specific antigen less than 10 ng/ml and normal digital rectal examination To compare prospect ively the diagnostic performance of a biparametric ( T2‐weighted imaging [ T2WI ] and diffusion‐weighted imaging [ DWI ] ) 1.5‐T fast magnetic resonance imaging ( fMRI ) protocol with the st and ard 3.0‐T multiparametric MRI ( mpMRI ) protocol of the European Society of Urological Imaging ( ESUR ) in men referred for a prostate biopsy Background Only sparse literature investigates the reproducibility and repeatability of relaxometry methods in MRI . However , statistical data on reproducibility and repeatability of any quantitative method is essential for clinical application . Purpose To evaluate the reproducibility and repeatability of two-dimensional fast imaging with steady-state free precession MR fingerprinting in vivo in human brains . Material s and Methods Two-dimensional section-selective MR fingerprinting based on a steady-state free precession sequence with an external radiofrequency transmit field , or B1 + , correction was used to generate T1 and T2 maps . This prospect i ve study was conducted between July 2017 and January 2018 with 10 scanners from a single manufacturer , including different models , at four different sites . T1 and T2 relaxation times and their variation across scanners ( reproducibility ) as well as across repetitions on a scanner ( repeatability ) were analyzed . The relative deviations of T1 and T2 to the average ( 95 % confidence interval ) were calculated for several brain compartments . Results Ten healthy volunteers ( mean age ± st and ard deviation , 28.5 years ± 6.9 ; eight men , two women ) participated in this study . Reproducibility and repeatability of T1 and T2 measures in the human brain varied across brain compartments ( 1.8%-20.9 % ) and were higher in solid tissues than in the cerebrospinal fluid . T1 measures in solid tissue brain compartments were more stable compared with T2 measures . The half-widths of the confidence intervals for relative deviations were 3.4 % for mean T1 and 8.0 % for mean T2 values across scanners . Intrascanner repeatability half-widths of the confidence intervals for relative deviations were in the range of 2.0%-3.1 % for T1 and 3.1%-7.9 % for T2 . Conclusion This study provides values on reproducibility and repeatability of T1 and T2 relaxometry measured with fast imaging with steady-state free precession MR fingerprinting in brain tissues of healthy volunteers . Reproducibility and repeatability are considerably higher in solid brain compartments than in cerebrospinal fluid and are higher for T1 than for T2 . © RSNA , 2019 Online supplemental material is available for this article . See also the editorial by Barkhof and Parker in this issue BACKGROUND Multiparametric magnetic resonance imaging ( mpMRI ) may have a role in detecting clinical ly significant prostate cancer in men with raised serum prostate-specific antigen levels . Variations in technique and the interpretation of images have contributed to inconsistency in its reported performance characteristics . OBJECTIVE Our aim was to make recommendations on a st and ardised method for the conduct , interpretation , and reporting of prostate mpMRI for prostate cancer detection and localisation . DESIGN , SETTING , AND PARTICIPANTS A consensus meeting of 16 European prostate cancer experts was held that followed the UCLA-R AND Appropriateness Method and facilitated by an independent chair . MEASUREMENT Before the meeting , 520 items were scored for " appropriateness " by panel members , discussed face to face , and rescored . RESULTS AND LIMITATIONS Agreement was reached in 67 % of 260 items related to imaging sequence parameters . T2-weighted , dynamic contrast-enhanced , and diffusion-weighted MRI were the key sequences incorporated into the minimum requirements . Consensus was also reached on 54 % of 260 items related to image interpretation and reporting , including features of malignancy on individual sequences . A 5-point scale was agreed on for communicating the probability of malignancy , with a minimum of 16 prostatic regions of interest , to include a pictorial representation of suspicious foci . Limitations relate to consensus methodology . Dominant personalities are known to affect the opinions of the group and were countered by a neutral chairperson . CONCLUSIONS Consensus was reached on a number of areas related to the conduct , interpretation , and reporting of mpMRI for the detection , localisation , and characterisation of prostate cancer . Before optimal dissemination of this technology , these outcomes will require formal validation in prospect i ve trials |
12,930 | 28,666,319 | The extent of SCD in CRT-P patients significantly increased in studies with higher percentage of males , ischaemic cardiomyopathy and NYHA class 3 .
Conclusion Overall , compared with CRT-D patients , unadjusted mortality rate was almost two-fold higher in CRT-P recipients , with SCD representing one third of the excess mortality .
Rate of SCD was significantly higher in certain subgroups ( males , ischaemic cardiomyopathy , NYHA class 3 ) , where a CRT-D may be of more pronounced benefit . | Aims The additional benefit of a defibrillator in cardiac resynchronization therapy ( CRT ) patients is a matter of debate .
Cause-of-death analysis in a CRT population has been recently proposed as a useful approach to gain insight into this problem .
We performed a systematic review and meta- analysis looking at cause of death in studies involving CRT subjects with ( CRT-D ) or without ( CRT-P ) a defibrillator . | BACKGROUND Biventricular ( BiV ) stimulation is the preferred means of delivering cardiac resynchronization therapy ( CRT ) , although left ventricular (LV)-only stimulation might be as safe and effective . B-LEFT HF is a prospect i ve , multicenter , r and omized , double-blind study aim ed to examine whether LV-only is noninferior to BiV pacing regarding clinical and echocardiographic responses . METHODS B-LEFT HF r and omly assigned 176 CRT-D recipients , in New York Heart Association class III or IV , with an LV ejection fraction < or = 35 % and QRS > or = 130 milliseconds , to a BiV ( n = 90 ) versus LV ( n = 86 ) stimulation group . Clinical status and echocardiograms were analyzed at baseline and 6 months after CRT-D implant to test the noninferiority of LV-only compared with BiV stimulation . RESULTS The proportion of responders was in line with current literature on CRT , with improvement in heart failure composite score in 76.2 % and 74.7 % of patients in BiV and LV groups , respectively . Comparing LV versus BiV pacing , the small differences in response rates and corresponding 95 % CI indicated that LV pacing was noninferior to BiV pacing for a series of response criteria ( combination of improvement in New York Heart Association and reverse remodeling , improvement in heart failure composite score , reduction in LV end-systolic volume of at least 10 % ) , both at intention-to-treat and at per- protocol analysis . CONCLUSIONS Left ventricular-only pacing is noninferior to BiV pacing in a 6-month follow-up with regard to clinical and echocardiographic responses . Left ventricular pacing may be considered as a clinical alternative option to BiV pacing Aims The choice of resynchronization therapy between with ( CRT-D ) and without ( CRT-P ) a defibrillator remains a contentious issue . Cause-of-death analysis among CRT-P , compared with CRT-D , patients could help evaluate the extent to which CRT-P patients would have additionally benefited from a defibrillator in a daily clinical practice . Methods and results A total of 1705 consecutive patients implanted with a CRT ( CRT-P : 535 and CRT-D : 1170 ) between 2008 and 2010 were enrolled in CeRtiTuDe , a multicentric prospect i ve follow-up cohort study , with specific adjudication for causes of death at 2 years . Patients with CRT-P compared with CRT-D were older ( P < 0.0001 ) , less often male ( P < 0.0001 ) , more symptomatic ( P = 0.0005 ) , with less coronary artery disease ( P = 0.003 ) , wider QRS ( P = 0.002 ) , more atrial fibrillation ( P < 0.0001 ) , and more co-morbidities ( P = 0.04 ) . At 2-year follow-up , the annual overall mortality rate was 83.80 [ 95 % confidence interval ( CI ) 73.41–94.19 ] per 1000 person-years . The crude mortality rate among CRT-P patients was double compared with CRT-D ( relative risk 2.01 , 95 % CI 1.56–2.58 ) . In a Cox proportional hazards regression analysis , CRT-P remained associated with increased mortality ( hazard ratio 1.54 , 95 % CI 1.07–2.21 , P = 0.0209 ) , although other potential confounders may persist . By cause-of-death analysis , 95 % of the excess mortality among CRT-P subjects was related to an increase in non-sudden death . Conclusion When compared with CRT-D patients , excess mortality in CRT-P recipients was mainly due to non-sudden death . Our findings suggest that CRT-P patients , as currently selected in routine clinical practice , would not potentially benefit with the addition of a defibrillator Background — The Sudden Cardiac Death in Heart Failure Trial ( SCD-HeFT ) demonstrated that implantable cardioverter-defibrillator ( ICD ) therapy reduces all-cause mortality in patients with New York Heart Association class II/III heart failure and a left ventricular ejection fraction ≤35 % on optimal medical therapy . Whether ICD therapy reduced sudden death caused by ventricular tachyarrhythmias without affecting heart failure deaths in this population is unknown . Methods and Results — SCD-HeFT r and omized 2521 subjects to placebo , amiodarone , or shock-only , single-lead ICD therapy . Over a median follow-up of 45.5 months , a total of 666 deaths occurred , which were review ed by an Events Committee and initially categorized as cardiac or noncardiac . Cardiac deaths were further adjudicated as result ing from sudden death presumed to be ventricular tachyarrhythmic , bradyarrhythmia , heart failure , or other cardiac causes . ICD therapy significantly reduced cardiac mortality compared with placebo ( adjusted hazard ratio , 0.76 ; 95 % confidence interval , 0.60 to 0.95 ) and tachyarrhythmia mortality ( adjusted hazard ratio , 0.40 ; 95 % confidence interval , 0.27 to 0.59 ) and had no impact on mortality result ing from heart failure or noncardiac causes . The cardiac and tachyarrhythmia mortality reductions were evident in subjects with New York Heart Association class II but not in subjects with class III heart failure . The reduction in tachyarrhythmia mortality with ICD therapy was similar in subjects with ischemic and nonischemic disease . Compared with placebo , amiodarone had no significant effect on any mode of death . Conclusions — ICD therapy reduced cardiac mortality and sudden death presumed to be ventricular tachyarrhythmic in SCD-HeFT and had no effect on heart failure mortality . Amiodarone had no effect on all-cause mortality or its cause-specific components , except an increase in non-cardiac mortality in class III patients . Clinical Trial Registration Information— URL : http://www . clinical trials.gov . Unique identifier : NCT00000609 The number needed to treat ( NNT ) is a simple measure of a treatment 's impact , increasingly reported in r and omized trials and observational studies . Its calculation in studies involving varying follow-up times or recurrent outcomes has been criticized . We discuss the NNT in these context s , illustrating using several published studies . The computation of the NNT is founded on the cumulative incidence of the outcome . Instead , several published studies use simple proportions that do not account for varying follow-up times , or use incidence rates per person-time . We show that these approaches can lead to erroneous values of the NNT and misleading interpretations . For example , after converting the incidence rate to a cumulative incidence , we show that a trial reporting a NNT of 4 " to prevent one exacerbation in 1 year " should have reported a NNT of 9 . A survey of all papers reporting NNT , published in four major medical journals in 2009 , found that 6 out of all 10 papers involving varying follow-up times did not correctly estimate the NNT . As the " number needed to treat " becomes increasingly used in complex studies and in the comparative effectiveness of therapies , its accurate estimation and interpretation become crucial to avoid erroneous clinical and public health decisions Objective : To compare the effects of cardiac resynchronisation therapy ( CRT ) in patients with heart failure ( HF ) in either atrial fibrillation ( AF ) or sinus rhythm ( SR ) . Design : Prospect i ve observational study . Patients : 295 consecutive patients with HF ( permanent AF in 66 , paroxysmal AF in 20 , SR in 209 ; New York Heart Association ( NYHA ) class III or IV ; left ventricular ejection fraction ( LVEF ) ⩽35 % , QRS ⩾120 ms ) . Interventions : All patients underwent CRT without atrioventricular junction ablation . Main outcome measures : The primary end point was the composite of cardiovascular death or unplanned hospitalisation for major cardiovascular events . Secondary end points included the composite of cardiovascular death or hospitalisation for worsening HF . Cardiovascular mortality , total mortality and changes in NYHA class , 6-minute walking distance , quality of life ( Minnesota Living with Heart Failure question naire ) and echocardiographic variables were also considered . Results : Over a follow-up period of up to 6.8 years , no differences emerged between patients in AF or SR in any of the mortality or morbidity end points . The AF and SR groups derived similar improvements in mean NYHA class ( −1.3 vs –1.2 ) , 6-minute walking distance ( 92.3 vs 78.4 m ) and quality of life scores ( −25.2 vs –18.7 ) ( all p<0.001 ) . In both the AF and the SR groups , reductions were seen in left ventricular end-systolic ( −25.9 vs –34.5 ml , both p<0.001 ) and end-diastolic ( −20.2 ml , p = 0.001 vs 26.2 ml , p<0.001 ) volumes and improvements in LVEF ( 4.69 % vs 7.86 % , both p<0.001 ) . Conclusions : Cardiac resynchronisation therapy leads to similar prognostic and symptomatic benefits in patients in AF and SR , even without atrioventricular junction ablation . Echocardiographic improvements are also comparable Background —Cardiac resynchronization therapy ( CRT ) decreases mortality , improves functional status , and induces reverse left ventricular remodeling in selected population s with heart failure . These benefits have been noted with both CRT-pacemakers as well as those devices with defibrillator backup ( CRT-D ) . However , there are little data comparing mortality between these 2 device types . Methods and Results —REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction ( REVERSE ) was a multicenter , r and omized trial of CRT among patients with mild heart failure . Long-term annual follow-up for 5 years was preplanned . The present analysis was confined to the 419 patients who were r and omized to active CRT group . CRT-pacemakers or CRT-D devices were implanted based on national guidelines at the time of enrollment , with 74 patients receiving CRT pacemaker devices and the remaining 345 patients receiving CRT-D devices . After 12 months of CRT , changes in the clinical composite score , left ventricular end systolic volume index , 6-minute walk time , and quality of life indices were similar between CRT pacemaker and CRT-D patients . However , long-term follow-up showed lower morality in the CRT-D group . Specifically , multivariable analysis showed that CRT-D ( hazard ratio , 0.35 ; P=0.003 ) was a strong independent predictor of survival . Female sex , longer unpaced QRS duration , and smaller baseline left ventricular end systolic volume index also were also associated with better survival . Conclusions —REVERSE demonstrated that the addition of implantable cardioverter-defibrillator therapy to CRT is associated with improved long-term survival compared with CRT pacing alone in mild heart failure . Clinical Trial Registration —URL : http:// clinical trials.gov . Unique Identifier : NCT00271154 AIMS The CArdiac REsynchronization-Heart Failure study r and omized patients with left ventricular ejection fraction < or = 35 % , markers of cardiac dyssynchrony , and persistent moderate or severe symptoms of heart failure despite pharmacological therapy , to implantation of a cardiac resynchronization therapy ( CRT ) device or not . The main study observed substantial benefits on morbidity and mortality during a mean follow-up of 29.4 months [ median 29.6 , interquartile range ( IQR ) 23.6 - 34.6 ] . Prior to study closure , an extension phase lasting a further 8 months ( allowing time for data analysis and presentation ) was declared during which cross-over was discouraged . METHODS AND RESULTS This was an extension of the already reported open-label r and omized trial described above . The primary outcome of the extension phase was all-cause mortality from the time of r and omization to completion of the extension phase . The secondary outcome was mode of death . The mean follow-up was 37.4 months ( median 37.6 , IQR 31.5 - 42.5 , range 26.1 - 52.6 months ) . There were 154 deaths ( 38.1 % ) in 404 patients assigned to medical therapy and 101 deaths ( 24.7 % ) in 409 patients assigned to CRT ( hazard ratio 0.60 , 95 % CI 0.47 - 0.77 , P<0.0001 ) without evidence of heterogeneity in pre-specified subgroups . A reduction in the risk of death due to heart failure ( 64 vs. 38 deaths ; hazard ratio 0.55 , 95 % CI 0.37 - 0.82 , P=0.003 ) and sudden death was observed ( 55 vs. 32 ; hazard ratio 0.54 , 95 % CI 0.35 - 0.84 , P=0.005 ) . CONCLUSION The benefits of CRT observed in the main trial persist or increase with longer follow-up . Reduction in mortality was due to fewer deaths both from worsening heart failure and from sudden death BACKGROUND Cardiac resynchronization reduces symptoms and improves left ventricular function in many patients with heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony . We evaluated its effects on morbidity and mortality . METHODS Patients with New York Heart Association class III or IV heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony who were receiving st and ard pharmacologic therapy were r and omly assigned to receive medical therapy alone or with cardiac resynchronization . The primary end point was the time to death from any cause or an unplanned hospitalization for a major cardiovascular event . The principal secondary end point was death from any cause . RESULTS A total of 813 patients were enrolled and followed for a mean of 29.4 months . The primary end point was reached by 159 patients in the cardiac-resynchronization group , as compared with 224 patients in the medical-therapy group ( 39 percent vs. 55 percent ; hazard ratio , 0.63 ; 95 percent confidence interval , 0.51 to 0.77 ; P<0.001 ) . There were 82 deaths in the cardiac-resynchronization group , as compared with 120 in the medical-therapy group ( 20 percent vs. 30 percent ; hazard ratio 0.64 ; 95 percent confidence interval , 0.48 to 0.85 ; P<0.002 ) . As compared with medical therapy , cardiac resynchronization reduced the interventricular mechanical delay , the end-systolic volume index , and the area of the mitral regurgitant jet ; increased the left ventricular ejection fraction ; and improved symptoms and the quality of life ( P<0.01 for all comparisons ) . CONCLUSIONS In patients with heart failure and cardiac dyssynchrony , cardiac resynchronization improves symptoms and the quality of life and reduces complications and the risk of death . These benefits are in addition to those afforded by st and ard pharmacologic therapy . The implantation of a cardiac-resynchronization device should routinely be considered in such patients CONTEXT Cardiac resynchronization therapy ( CRT ) through biventricular pacing is an effective treatment for heart failure ( HF ) with a wide QRS ; however , the outcomes of patients requiring CRT and implantable cardioverter defibrillator ( ICD ) therapy are unknown . OBJECTIVE To examine the efficacy and safety of combined CRT and ICD therapy in patients with New York Heart Association ( NYHA ) class III or IV congestive HF despite appropriate medical management . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , parallel-controlled trial conducted from October 1 , 1999 , to August 31 , 2001 , of 369 patients with left ventricular ejection fraction of 35 % or less , QRS duration of 130 ms , at high risk of life-threatening ventricular arrhythmias , and in NYHA class III ( n = 328 ) or IV ( n = 41 ) despite optimized medical treatment . INTERVENTIONS Of 369 r and omized patients who received devices with combined CRT and ICD capabilities , 182 were controls ( ICD activated , CRT off ) and 187 were in the CRT group ( ICD activated , CRT on ) . MAIN OUTCOME MEASURES The primary double-blind study end points were changes between baseline and 6 months in quality of life , functional class , and distance covered during a 6-minute walk . Additional outcome measures included changes in exercise capacity , plasma neurohormones , left ventricular function , and overall HF status . Survival , incidence of ventricular arrhythmias , and rates of hospitalization were also compared . RESULTS At 6 months , patients assigned to CRT had a greater improvement in median ( 95 % confidence interval ) quality of life score ( -17.5 [ -21 to -14 ] vs -11.0 [ -16 to -7 ] , P = .02 ) and functional class ( -1 [ -1 to -1 ] vs 0 [ -1 to 0 ] , P = .007 ) than controls but were no different in the change in distance walked in 6 minutes ( 55 m [ 44 - 79 ] vs 53 m [ 43 - 75 ] , P = .36 ) . Peak oxygen consumption increased by 1.1 mL/kg per minute ( 0.7 - 1.6 ) in the CRT group vs 0.1 mL/kg per minute ( -0.1 to 0.8 ) in controls ( P = .04 ) , although treadmill exercise duration increased by 56 seconds ( 30 - 79 ) in the CRT group and decreased by 11 seconds ( -55 to 12 ) in controls ( P<.001 ) . No significant differences were observed in changes in left ventricular size or function , overall HF status , survival , and rates of hospitalization . No proarrhythmia was observed and arrhythmia termination capabilities were not impaired . CONCLUSIONS Cardiac resynchronization improved quality of life , functional status , and exercise capacity in patients with moderate to severe HF , a wide QRS interval , and life-threatening arrhythmias . These improvements occurred in the context of underlying appropriate medical management without proarrhythmia or compromised ICD function Background — The Multicenter Automatic Defibrillator Implantation Trial II ( MADIT-II ) showed a significant 31 % reduction in the risk of death with primary implantable cardioverter-defibrillator ( ICD ) therapy during a median follow-up of 1.5 years . However , currently there are no data on the long-term efficacy of primary defibrillator therapy . Methods and Results — MADIT-II enrolled 1232 patients with ischemic left ventricular dysfunction who were r and omized to ICD and non-ICD medical therapy and were followed up through November 2001 . For the present long-term study , we acquired posttrial mortality data through March 2009 for all study participants ( median follow-up , 7.6 years ) . Multivariate Cox proportional hazards regression modeling was performed to calculate the hazard ratio for ICD versus non-ICD therapy during long-term follow-up . At 8 years of follow-up , the cumulative probability of all-cause mortality was 49 % among patients treated with an ICD compared with 62 % among non-ICD patients ( P<0.001 ) . Multivariate analysis demonstrated that ICD therapy was associated with a significant long-term survival benefit ( hazard ratio for 0- through 8-year mortality=0.66 [ 95 % confidence interval , 0.56 to 0.78 ] ; P<0.001 ) . Treatment with an ICD was shown to be associated with a significant reduction in the risk of death during the early phase of the extended follow-up period ( 0 through 4 years : hazard ratio=0.61 [ 95 % confidence interval , 0.50 to 0.76 ] ; P<0.001 ) and with continued life-saving benefit during the late phase of follow-up ( 5 through 8 years : hazard ratio=0.74 [ 95 % confidence interval , 0.57 to 0.96 ] ; P=0.02 ) . Conclusions — Our findings demonstrate a sustained 8-year survival benefit with primary ICD therapy in the MADIT-II population BACKGROUND Sudden death from cardiac causes remains a leading cause of death among patients with congestive heart failure ( CHF ) . Treatment with amiodarone or an implantable cardioverter-defibrillator ( ICD ) has been proposed to improve the prognosis in such patients . METHODS We r and omly assigned 2521 patients with New York Heart Association ( NYHA ) class II or III CHF and a left ventricular ejection fraction ( LVEF ) of 35 percent or less to conventional therapy for CHF plus placebo ( 847 patients ) , conventional therapy plus amiodarone ( 845 patients ) , or conventional therapy plus a conservatively programmed , shock-only , single-lead ICD ( 829 patients ) . Placebo and amiodarone were administered in a double-blind fashion . The primary end point was death from any cause . RESULTS The median LVEF in patients was 25 percent ; 70 percent were in NYHA class II , and 30 percent were in class III CHF . The cause of CHF was ischemic in 52 percent and nonischemic in 48 percent . The median follow-up was 45.5 months . There were 244 deaths ( 29 percent ) in the placebo group , 240 ( 28 percent ) in the amiodarone group , and 182 ( 22 percent ) in the ICD group . As compared with placebo , amiodarone was associated with a similar risk of death ( hazard ratio , 1.06 ; 97.5 percent confidence interval , 0.86 to 1.30 ; P=0.53 ) and ICD therapy was associated with a decreased risk of death of 23 percent ( 0.77 ; 97.5 percent confidence interval , 0.62 to 0.96 ; P=0.007 ) and an absolute decrease in mortality of 7.2 percentage points after five years in the overall population . Results did not vary according to either ischemic or nonischemic causes of CHF , but they did vary according to the NYHA class . CONCLUSIONS In patients with NYHA class II or III CHF and LVEF of 35 percent or less , amiodarone has no favorable effect on survival , whereas single-lead , shock-only ICD therapy reduces overall mortality by 23 percent BACKGROUND Chronic right ventricular pacing has been reported to promote cardiac dyssynchrony . The PAVE trial prospect ively compared chronic biventricular pacing to right ventricular pacing in patients undergoing ablation of the AV node for management of atrial fibrillation with rapid ventricular rates . METHODS AND RESULTS One hundred and eighty-four patients requiring AV node ablation were r and omized to receive a biventricular pacing system ( n = 103 ) or a right ventricular pacing system ( n = 81 ) . The study endpoints were change in the 6-minute hallway walk test , quality of life , and left ventricular ejection fraction . Patient characteristics were similar ( 64 % male ; age : 69 + /- 10 years , ejection fraction : 0.46 + /- 0.16 ; 83 % , NYHA Class II or III ) . At 6 months postablation , patients treated with cardiac resynchronization had a significant improvement in 6-minute walk distance , ( 31 % ) above baseline ( 82.9 + /- 94.7 m ) , compared to patients receiving right ventricular pacing , ( 24 % ) above baseline ( 61.2 + /- 90.0 m ) ( P = 0.04 ) . There were no significant differences in the quality -of-life parameters . At 6 months postablation , the ejection fraction in the biventricular group ( 0.46 + /- 0.13 ) was significantly greater in comparison to patients receiving right ventricular pacing ( 0.41 + /- 0.13 , P = 0.03 ) . Patients with an ejection fraction < or=45 % or with NYHA Class II/III symptoms receiving a biventricular pacemaker appear to have a greater improvement in 6-minute walk distance compared to patients with normal systolic function or Class I symptoms . CONCLUSION For patients undergoing AV node ablation for atrial fibrillation , biventricular pacing provides a significant improvement in the 6-minute hallway walk test and ejection fraction compared to right ventricular pacing . These beneficial effects of cardiac resynchronization appear to be greater in patients with impaired systolic function or with symptomatic heart failure AIMS The aim of this study was to determine the relationship between improved ejection fraction ( EF ) and occurrence of arrhythmias in patients with cardiac resynchronization therapy devices with defibrillator function ( CRT-D ) . The hypothesis was that patients who experienced a marked improvement in EF also had fewer appropriate defibrillator interventions . METHODS AND RESULTS We analysed data of 270 patients from 2 prospect i ve registries with follow-up of ≥12 months and echocardiography performed ≥8 months after CRT-D implantation . The discriminator was whether left ventricular ejection fraction ( LVEF ) improved to > 35 % [ cut-off for primary prevention implantable cardioverter-defibrillator ( ICD ) implantation ] . Mean age was 61±11 years , LVEF 22±5 % , and follow-up 40±22 months . Ischaemic cardiomyopathy was present in 48 % , and secondary prevention indication was present in 25 % . Implantable cardioverter-defibrillator interventions were delivered to 35 % of patients . Echocardiography ( 20±15 months after implantation ) showed an improvement in LVEF from 22 % ( SD 5.4 % ) to 30 % ( SD 9.8 % ) . Improvement to > 35 % was seen in 21 % of patients . Those who improved to > 35 % had fewer ICD interventions than those who did not ( 23 vs.38 % ; P-value 0.03 ) . Analysing only patients with a primary prevention indication and stratifying again in patients with and without improvement of LVEF to > 35 % , the latter had highly significant more ICD-therapies ( 6 vs. 31 % ; P-value 0.0008 ) . CONCLUSION Patients with CRT-D for primary prevention , whose LVEF improved to > 35 % during mid-term follow-up , are at low risk of first ICD therapies beyond year 1 . If similar findings are reported in other patient cohorts , this might impact on decision-making at the time of battery depletion BACKGROUND Although data on the mode of death of implantable cardioverter-defibrillator ( ICD ) and cardiac resynchronization therapy with defibrillator ( CRT-D ) patients have been examined in r and omized clinical trials , in routine clinical practice data are scarce . To provide reasonable expectations and prognosis for patients and physicians , this study assessed the mode of death in routine clinical practice . OBJECTIVE To assess the mode of death in ICD/CRT-D recipients in routine clinical practice . METHODS All patients who underwent an ICD or CRT-D implantation at the Leiden University Medical Center , the Netherl and s , between 1996 and 2010 were included . Patients were divided into primary prevention ICD , secondary prevention ICD , and CRT-D patients . For patients who died during follow-up , the mode of death was retrieved from hospital and general practitioner records and categorized according to a predetermined classification : heart failure death , other cardiac death , sudden death , noncardiac death , and unknown death . RESULTS A total of 2859 patients were included in the analysis . During a median follow-up of 3.4 years ( interquartile range 1.7 - 5.7 years ) , 107 ( 14 % ) primary prevention ICD , 253 ( 28 % ) secondary prevention ICD , and 302 ( 25 % ) CRT-D recipients died . The 8-year cumulative incidence of all-cause mortality was 39.9 % ( 95 % confidence interval 37.0%-42.9 % ) . Heart failure death and noncardiac death were the most common modes of death for all groups . Sudden death accounted for approximately 7%-8 % of all deaths . CONCLUSION For all patients , heart failure and noncardiac death are the most common modes of death . The proportion of patients who died suddenly was low and comparable for primary and secondary ICD and CRT-D patients AIMS The aim of this study was to investigate the 12-month incidence , predictive factors , and prognosis of sustained ventricular tachycardia ( VT ) in chronic heart failure patients implanted with biventricular pacemakers without a back-up defibrillator ( CRT-P ) , assessed by continuous intracardiac ventricular electrograms . METHODS AND RESULTS The Mona Lisa study , a prospect i ve , multicentre , cohort study , design ed to determine the incidence of sustained VT and its prognostic impact in CRT-P recipients within the year after implant enrolled 198 patients with moderate or severe chronic heart failure , despite optimal pharmacological therapy . An independent committee review ed the data from all arrhythmic episodes as well as causes of death according to predefined criteria . During a mean follow-up of 9.8 + /- 3.1 months after implantation , 8 patients experienced at least one episode of sustained VT [ 4.3 % ; 95 % confidence interval ( CI ) , 1.1 - 7.5 ] and 21 deaths occurred , giving a 12-month mortality rate of 11.7 % ( 95 % CI , 6.4 - 16.9 ) . The presence of sustained VT was associated with a high risk of sudden cardiac death ( SCD ) and the lowest 12-month overall survival ( P < 0.0001 ) . CONCLUSION The incidence of sustained VT remains relatively low in the first year after CRT-P implantation , but when present appears closely associated with short-term adverse outcomes , especially SCD . This emphasizes the possible value of remote monitoring to detect high-risk patients for urgent upgrading Cardiac resynchronization therapy ( CRT ) leads to reverse ventricular remodelling , improved functional capacity , and better clinical outcome in patients with advanced chronic heart failure , reduced ejection fraction , and evidence of ventricular conduction delay , who are under optimal medical therapy . This study investigated whether these benefits can be extrapolated to older patients , typically not included in r and omized clinical trials OBJECTIVES To assess in patients with chronic heart failure the effect of cardiac resynchronization therapy ( CRT ) over 12 months ' follow-up the time course of the changes in functional and neurohormonal indices and to identify responders to CRT . METHODS Eighty-nine patients ( 74.1 + /- 1 years , left ventricular ejection fraction [ LVEF ] < 35 % ) , QRS complex duration > 150 ms , in stable New York Heart Association ( NYHA ) class III or IV on optimal medical treatment were prospect ively r and omized either in a control ( n = 45 ) or CRT ( n = 44 ) group and underwent clinical evaluation , cardiopulmonary exercise testing ( CPET ) , 2D-Echo , heart rate variability ( HRV ) , carotid baroreflex ( BRS ) , and BNP assessment s before and at 6- and 12-month follow-up . RESULTS In the CRT group , improvement of cardiac indices and BNP concentration were evident at medium term ( over 6 months ) follow-up , and these changes persisted on a longer term ( 12 months ) ( all P < 0.05 ) . Instead CPET indices and NYHA class improved after 12 months associated with restoration of HRV and BRS ( all P < 0.05 ) . We identified 26 responders to CRT according to changes in LVEF and diameters . Responders presented less depressed hemodynamic ( LVEF 25 + /- 1.0 vs 22 + /- 0.1 % ) , functional ( peak VO(2 ) 10.2 + /- 0.2 vs 6.9 + /- 0.3 ml/kg/min ) , and neurohormonal indices ( HRV 203.6 + /- 15.7 vs 147.6 + /- 10.ms , BRS 4.9 + /- 0.2 vs 3.6 + /- 0.3 ms/mmHg ) ( all P < 0.05 ) . In the multivariate analysis , peak VO(2 ) was the strongest predictor of responders . CONCLUSIONS Improvement in functional status is associated with restoration of neurohormonal reflex control at medium term . Less depressed functional status ( peak VO(2 ) ) was the strongest predictor of responders to CRT BACKGROUND We tested the hypothesis that prophylactic cardiac-resynchronization therapy in the form of biventricular stimulation with a pacemaker with or without a defibrillator would reduce the risk of death and hospitalization among patients with advanced chronic heart failure and intraventricular conduction delays . METHODS A total of 1520 patients who had advanced heart failure ( New York Heart Association class III or IV ) due to ischemic or nonischemic cardiomyopathies and a QRS interval of at least 120 msec were r and omly assigned in a 1:2:2 ratio to receive optimal pharmacologic therapy ( diuretics , angiotensin-converting-enzyme inhibitors , beta-blockers , and spironolactone ) alone or in combination with cardiac-resynchronization therapy with either a pacemaker or a pacemaker-defibrillator . The primary composite end point was the time to death from or hospitalization for any cause . RESULTS As compared with optimal pharmacologic therapy alone , cardiac-resynchronization therapy with a pacemaker decreased the risk of the primary end point ( hazard ratio , 0.81 ; P=0.014 ) , as did cardiac-resynchronization therapy with a pacemaker-defibrillator ( hazard ratio , 0.80 ; P=0.01 ) . The risk of the combined end point of death from or hospitalization for heart failure was reduced by 34 percent in the pacemaker group ( P<0.002 ) and by 40 percent in the pacemaker-defibrillator group ( P<0.001 for the comparison with the pharmacologic-therapy group ) . A pacemaker reduced the risk of the secondary end point of death from any cause by 24 percent ( P=0.059 ) , and a pacemaker-defibrillator reduced the risk by 36 percent ( P=0.003 ) . CONCLUSIONS In patients with advanced heart failure and a prolonged QRS interval , cardiac-resynchronization therapy decreases the combined risk of death from any cause or first hospitalization and , when combined with an implantable defibrillator , significantly reduces mortality BACKGROUND Biventricular ( BiV ) stimulation lowers morbidity and mortality in patients with drug-refractory congestive heart failure ( CHF ) , depressed left ventricular ( LV ) function , and ventricular dyssynchrony in absence of indication for permanent cardiac pacing . This pilot , single-blind , r and omized , cross-over study examined the safety and efficacy of upgrading conventional pacing systems to BiV stimulation in patients with advanced CHF . METHODS We included 56 patients in New York Heart Association ( NYHA ) functional classes III or IV despite optimal drug treatment and ventricular dyssynchrony ( interventriclar delay > 40 ms or LV preejection delay > 140 ms ) in need of pacemaker replacement . We compared the patients ' functional status , arrhythmias , and st and ard echocardiographic measurements during 3 months of conventional , single right ventricular ( RV ) versus 3 months of BiV stimulation . RESULTS There were 44 patients in the cross-over phase . QRS duration was shortened by 23 % and LV preejection delay by 16 % with BiV stimulation . NYHA functional class , 6-minute hall walk and quality of life score were significantly improved with BiV stimulation compared with single RV pacing by 18 % , 29 % , and 19 % , respectively . No significant difference was observed in the ventricular arrhythmia burden or LV reverse remodeling between the 2 periods . CONCLUSIONS This pilot study showed that upgrading from RV pacing to BiV pacing significantly improves symptoms and exercise tolerance in chronically paced patients with advanced CHF and mechanical dyssynchrony This multicenter longitudinal observational trial was design ed to analyze the long-term outcome of patients with heart failure ( HF ) treated with cardiac resynchronization therapy ( CRT ) alone or with implantable cardioverter-defibrillator ( ICD ) backup in a daily practice scenario . It is unknown whether the magnitude of survival benefits conferred by CRT in a daily practice scenario is comparable to what has been observed in r and omized controlled trials and whether this benefit is sustained over the long term . The outcome of 1,303 consecutive patients with ischemic or nonischemic cardiomyopathy on optimal pharmacologic therapy treated from August 1 , 1995 to August 1 , 2004 at 4 European centers with CRT alone ( 44 % ) or with ICD backup for symptomatic HF and prolonged QRS duration was assessed . Cumulative event-free survival was evaluated for a combined end point , defined as death from any cause , urgent transplantation , or implantation of a left ventricular assist device . The cumulative incidence of competing events , HF , sudden cardiac death , and noncardiac death , was also assessed . Event-free survival was similar across the different centers . At 1 and 5 years , cumulative event-free survivals were 92 % ( 95 % confidence interval [ CI ] 91 to 94 ) and 56 % ( 95 % CI 48 to 64 ) , respectively . The cumulative incidence of HF deaths was 25.1 % ( 95 % CI 19 to 31.7 ) , whereas that of sudden death was 9.5 % ( 95 % CI 5.1 to 15.7 ) . Using multivariate analysis , CRT with an ICD backup was associated with a nonsignificant decrease in mortality by 20 % ( hazard ratio 0.83 , 95 % CI 0.58 to 1.17 , p = 0.284 ) , with a highly significant protective effect against sudden cardiac death ( hazard ratio 0.04 , 95 % CI 0.04 to 0.28 , p < 0.002 ) . In conclusion , patients with advanced HF and a wide QRS complex routinely treated with CRT have a favorable long-term outcome that was reproducible at different centers . The leading cause of death in these patients remained HF , and this mode of death was competing with other causes in determining outcome . Total mortality was 20 % lower with ICD backup ( 95 % CI 42 % lower to 17 % higher ) due to a protective effect against sudden cardiac death BACKGROUND Previous studies have suggested that cardiac resynchronization achieved through atrial-synchronized biventricular pacing produces clinical benefits in patients with heart failure who have an intraventricular conduction delay . We conducted a double-blind trial to evaluate this therapeutic approach . METHODS Four hundred fifty-three patients with moderate-to-severe symptoms of heart failure associated with an ejection fraction of 35 percent or less and a QRS interval of 130 msec or more were r and omly assigned to a cardiac-resynchronization group ( 228 patients ) or to a control group ( 225 patients ) for six months , while conventional therapy for heart failure was maintained . The primary end points were the New York Heart Association functional class , quality of life , and the distance walked in six minutes . RESULTS As compared with the control group , patients assigned to cardiac resynchronization experienced an improvement in the distance walked in six minutes ( + 39 vs. + 10 m , P=0.005 ) , functional class ( P<0.001 ) , quality of life ( -18.0 vs. -9.0 points , P= 0.001 ) , time on the treadmill during exercise testing ( + 81 vs. + 19 sec , P=0.001 ) , and ejection fraction ( + 4.6 percent vs. -0.2 percent , P<0.001 ) . In addition , fewer patients in the group assigned to cardiac resynchronization than control patients required hospitalization ( 8 percent vs. 15 percent ) or intravenous medications ( 7 percent vs. 15 percent ) for the treatment of heart failure ( P<0.05 for both comparisons ) . Implantation of the device was unsuccessful in 8 percent of patients and was complicated by refractory hypotension , bradycardia , or asystole in four patients ( two of whom died ) and by perforation of the coronary sinus requiring pericardiocentesis in two others . CONCLUSIONS Cardiac resynchronization results in significant clinical improvement in patients who have moderate-to-severe heart failure and an intraventricular conduction delay AIMS To evaluate the long-term changes of clinical and echocardiographic parameters , the incidence of cardiac events and parameters associated with late cardiac events in ' super-responders ' to cardiac resynchronization therapy ( CRT ) with [ CRT defibrillator ( CRT-D ) ] or without defibrillator back-up . METHODS AND RESULTS In all consecutive patients treated with CRT in two Italian centres ( Trieste and Udine ) with left ventricular ejection fraction ( LVEF ) ≤0.35 at implantation ( Timp ) and LVEF > 0.50 1 and /or 2 years ( Tnorm ) after implantation , the long-term outcome and the evolution of echocardiographic parameters were assessed ; factors associated with a higher risk of cardiac events , defined as hospitalization or death for heart failure ( HF ) , sudden death , or CRT-D appropriate interventions , were also analysed . Among the 259 patients evaluated , 62 ( 24 % ) had LVEF ≥ 0.50 at Tnorm ( n = 44 with at 1 year , n = 18 at 2 years ) . During a mean follow-up of 68 ± 30 months , one cardiac death ( for HF ) and eight cardiovascular events ( two hospitalization for HF and six appropriate CRT-D interventions ) occurred . At the last echo evaluation ( Tfup ) performed 51 ± 26 months after Timp , LVEF was < 0.50 in five patients ( > 0.45 in four of them ) . At univariable analysis , only LV end-systolic volume evaluated at Tfup was associated with a higher risk of cardiac events during follow-up . CONCLUSION In ' super-responders ' to CRT long-term outcome is excellent . However , cardiac events , mainly CRT-D appropriate interventions , can occur despite the persistence of LVEF > 0.50 . Early identification of these patients is still an unsolved issue BACKGROUND The benefit of an implantable cardioverter-defibrillator ( ICD ) in patients with symptomatic systolic heart failure caused by coronary artery disease has been well documented . However , the evidence for a benefit of prophylactic ICDs in patients with systolic heart failure that is not due to coronary artery disease has been based primarily on subgroup analyses . The management of heart failure has improved since the l and mark ICD trials , and many patients now receive cardiac resynchronization therapy ( CRT ) . METHODS In a r and omized , controlled trial , 556 patients with symptomatic systolic heart failure ( left ventricular ejection fraction , ≤35 % ) not caused by coronary artery disease were assigned to receive an ICD , and 560 patients were assigned to receive usual clinical care ( control group ) . In both groups , 58 % of the patients received CRT . The primary outcome of the trial was death from any cause . The secondary outcomes were sudden cardiac death and cardiovascular death . RESULTS After a median follow-up period of 67.6 months , the primary outcome had occurred in 120 patients ( 21.6 % ) in the ICD group and in 131 patients ( 23.4 % ) in the control group ( hazard ratio , 0.87 ; 95 % confidence interval [ CI ] , 0.68 to 1.12 ; P=0.28 ) . Sudden cardiac death occurred in 24 patients ( 4.3 % ) in the ICD group and in 46 patients ( 8.2 % ) in the control group ( hazard ratio , 0.50 ; 95 % CI , 0.31 to 0.82 ; P=0.005 ) . Device infection occurred in 27 patients ( 4.9 % ) in the ICD group and in 20 patients ( 3.6 % ) in the control group ( P=0.29 ) . CONCLUSIONS In this trial , prophylactic ICD implantation in patients with symptomatic systolic heart failure not caused by coronary artery disease was not associated with a significantly lower long-term rate of death from any cause than was usual clinical care . ( Funded by Medtronic and others ; DANISH Clinical Trials.gov number , NCT00542945 . ) OBJECTIVES The authors investigated predictors of left ventricular ejection fraction ( LVEF ) super-response to cardiac resynchronization therapy with defibrillator ( CRT-D ) and whether super-response translated into improved event-free survival in patients with mildly symptomatic heart failure ( HF ) . BACKGROUND Few data exist on predictors of super-response to CRT-D and associated morbidity and mortality in mildly symptomatic HF population s. METHODS Patients were assigned to CRT-D with paired echocardiograms at baseline and at 12 months ( n = 752 ) . Super-response was defined by the top quartile of LVEF change . Best-subset regression analysis identified predictors of LVEF super-response . Kaplan-Meier survival analysis and Cox proportional hazards regression were performed to investigate associations of response category with development of nonfatal HF event or all-cause death . RESULTS All 191 super-responders experienced an LVEF increase of ≥14.5 % ( mean LVEF increase 17.5 ± 2.7 % ) . Six predictors were associated with LVEF super-response to CRT-D therapy : female sex ( odds ratio [ OR ] : 1.96 ; p = 0.001 ) , no prior myocardial infa rct ion ( OR : 1.80 ; p = 0.005 ) , QRS duration ≥150 ms ( OR : 1.79 ; p = 0.007 ) , left bundle branch block ( OR : 2.05 ; p = 0.006 ) , body mass index < 30 kg/m(2 ) ( OR : 1.51 ; p = 0.035 ) , and smaller baseline left atrial volume index ( OR : 1.47 ; p < 0.001 ) . Cumulative probability of HF or all-cause death at 2 years was 4 % in super-responders , 11 % in responders , and 26 % in hypo-responders ( log-rank p < 0.001 overall ) . In multivariate analysis , hyporesponse was associated with increased risk of HF or all-cause death , compared with super-response ( hazard ratio : 5.25 ; 95 % confidence interval : 2.01 to 13.74 ; p = 0.001 ) . CONCLUSIONS Six baseline factors predicted LVEF super-response in CRT-D-treated patients with mild HF . Super-response was associated with reduced risk of subsequent cardiac events . ( Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy [ MADIT-CRT ] ; NCT00180271 ) |
12,931 | 29,405,918 | Mindfulness-Based Cognitive Therapy ( MBCT ) , Mindfulness-Based Stress Reduction ( MBSR ) , Acceptance and Commitment Therapy ( ACT ) , Dialectical Behavior Therapy ( DBT ) , and extended Behaviour Activation ( eBA ) showed acceptable cost-effectiveness and cost-utility ratios .
There is some evidence that MBCT , MBSR , ACT , DBT , and eBA are efficient from a societal or a third-party payer perspective .
No economic analysis was found for many third-wave therapies . | The term third-wave cognitive behavioral therapy ( CBT ) encompasses new forms of CBT that both extend and innovate within CBT .
Most third-wave therapies have been subject to r and omized controlled trials ( RCTs ) focused on clinical effectiveness ; however , the number and quality of economic evaluations in these RCTs has been unknown and may be few .
Evidence about efficiency of these therapies may help support decisions on efficient allocation of re sources in health policies .
The main aim of this study was to systematic ally review the economic impact of third-wave therapies in the treatment of patients with physical or mental conditions . | OBJECTIVE Our aim was to assess cost-effectiveness of mindfulness-based cognitive therapy ( MBCT ) compared with enhanced usual care ( EUC ) in treating patients with persistent medically unexplained symptoms(MUS ) . METHODS A full economic evaluation with a one year time horizon was performed from a societal perspective . Costs were assessed by prospect i ve cost diaries . Health-related Quality of Life was measured using SF-6D . Outcomes were costs per Quality -Adjusted Life Year ( QALY ) . Bootstrap simulations were performed to obtain mean costs , QALY scores and incremental cost-effectiveness ratios ( ICERs ) . RESULTS MBCT participants ( n=55 ) had lower hospital costs and higher mental health care costs than patients who received EUC ( n=41 ) . Mean bootstrapped costs for MBCT were € 6269 , and € 5617 for EUC ( 95 % uncertainty interval for difference : -€1576 ; € 2955 ) . QALYs were 0.674 for MBCT and 0.663 for EUC . MBCT was on average more effective and more costly than EUC , result ing in an ICER of € 56,637 per QALY gained . At a willingness to pay of € 80,000 per QALY , the probability that MBCT is cost-effective is 57 % . CONCLUSION Total costs were not statistically significantly different between MBCT and EUC . However , MBCT seemed to cause a shift in the use of health care re sources as mental health care costs were higher and hospital care costs lower in the MBCT condition . Due to the higher drop-out in the EUC condition the cost-effectiveness of MBCT might have been underestimated . The shift in health care use might lead to more effective care for patients with persistent MUS . The longer-term impact of MBCT for patients with persistent MUS needs to be further studied Summary Background Depression is a common , debilitating , and costly disorder . Many patients request psychological therapy , but the best- evidence d therapy — cognitive behavioural therapy (CBT)—is complex and costly . A simpler therapy — behavioural activation (BA)—might be as effective and cheaper than is CBT . We aim ed to establish the clinical efficacy and cost-effectiveness of BA compared with CBT for adults with depression . Methods In this r and omised , controlled , non-inferiority trial , we recruited adults aged 18 years or older meeting Diagnostic and Statistical Manual of Mental Disorders IV criteria for major depressive disorder from primary care and psychological therapy services in Devon , Durham , and Leeds ( UK ) . We excluded people who were receiving psychological therapy , were alcohol or drug dependent , were acutely suicidal or had attempted suicide in the previous 2 months , or were cognitively impaired , or who had bipolar disorder or psychosis or psychotic symptoms . We r and omly assigned participants ( 1:1 ) remotely using computer-generated allocation ( minimisation used ; stratified by depression severity [ Patient Health Question naire 9 ( PHQ-9 ) score of < 19 vs ≥19 ] , antidepressant use , and recruitment site ) to BA from junior mental health workers or CBT from psychological therapists . R and omisation done at the Peninsula Clinical Trials Unit was concealed from investigators . Treatment was given open label , but outcome assessors were masked . The primary outcome was depression symptoms according to the PHQ-9 at 12 months . We analysed all those who were r and omly allocated and had complete data ( modified intention to treat [ mITT ] ) and also all those who were r and omly allocated , had complete data , and received at least eight treatment sessions ( per protocol [ PP ] ) . We analysed safety in the mITT population . The non-inferiority margin was 1·9 PHQ-9 points . This trial is registered with the ISCRTN registry , number IS RCT N27473954 . Findings Between Sept 26 , 2012 , and April 3 , 2014 , we r and omly allocated 221 ( 50 % ) participants to BA and 219 ( 50 % ) to CBT . 175 ( 79 % ) participants were assessable for the primary outcome in the mITT population in the BA group compared with 189 ( 86 % ) in the CBT group , whereas 135 ( 61 % ) were assessable in the PP population in the BA group compared with 151 ( 69 % ) in the CBT group . BA was non-inferior to CBT ( mITT : CBT 8·4 PHQ-9 points [ SD 7·5 ] , BA 8·4 PHQ-9 points [ 7·0 ] , mean difference 0·1 PHQ-9 points [ 95 % CI −1·3 to 1·5 ] , p=0·89 ; PP : CBT 7·9 PHQ-9 points [ 7·3 ] ; BA 7·8 [ 6·5 ] , mean difference 0·0 PHQ-9 points [ –1·5 to 1·6 ] , p=0·99 ) . Two ( 1 % ) non-trial-related deaths ( one [ 1 % ] multidrug toxicity in the BA group and one [ 1 % ] cancer in the CBT group ) and 15 depression-related , but not treatment-related , serious adverse events ( three in the BA group and 12 in the CBT group ) occurred in three [ 2 % ] participants in the BA group ( two [ 1 % ] patients who overdosed and one [ 1 % ] who self-harmed ) and eight ( 4 % ) participants in the CBT group ( seven [ 4 % ] who overdosed and one [ 1 % ] who self-harmed ) . Interpretation We found that BA , a simpler psychological treatment than CBT , can be delivered by junior mental health workers with less intensive and costly training , with no lesser effect than CBT . Effective psychological therapy for depression can be delivered without the need for costly and highly trained professionals . Funding National Institute for Health Research The aim of this study was to analyze the cost utility of a group-based form of acceptance and commitment therapy ( GACT ) in patients with fibromyalgia ( FM ) compared with patients receiving recommended pharmacological treatment ( RPT ) or on a waiting list ( WL ) . The data were derived from a previously published study , a r and omized controlled trial that focused on clinical outcomes . Health economic outcomes included health-related quality of life and health care use at baseline and at 6-month follow-up using the EuroQoL and the Client Service Receipt Inventory , respectively . Analyses included quality -adjusted life years , direct and indirect cost differences , and incremental cost effectiveness ratios . A total of 156 FM patients were r and omized ( 51 GACT , 52 RPT , 53 WL ) . GACT was related to significantly less direct costs over the 6-month study period compared with both control arms ( GACT € 824.2 ± 1,062.7 vs RPT € 1,730.7 ± 1,656.8 vs WL € 2,462.7 ± 2,822.0 ) . Lower direct costs for GACT compared with RPT were due to lower costs from primary care visits and FM-related medications . The incremental cost effectiveness ratios were dominant in the completers ' analysis and remained robust in the sensitivity analyses . In conclusion , acceptance and commitment therapy appears to be a cost-effective treatment compared with RPT in patients with FM . PERSPECTIVE Decision-makers have to prioritize their budget on the treatment option that is the most cost effective for the management of a specific patient group . From government as well as health care perspectives , this study shows that a GACT is more cost effective than pharmacological treatment in management of FM Objective To explore participant views on acceptability , mechanisms of change and impact of behavioural activation ( BA ) delivered by junior mental health workers ( MHWs ) versus cognitive behavioural therapy ( CBT ) delivered by professional psychotherapists . Design Semistructured qualitative interviews analysed using a framework approach . Participants 36 participants with major depressive disorder purposively sample d from a r and omised controlled trial of BA versus CBT ( the COBRA trial ) . Setting Primary care psychological therapies services in Devon , Durham and Leeds , UK . Results Elements of therapy considered to be beneficial included its length and regularity , the opportunity to learn and not dwelling on the past . Homework was an important , although challenging aspect of treatment . Therapists were perceived as experts who played an important role in treatment . For some participants the most important element of therapy was having someone to talk to , but for others the specific factors associated with BA and CBT were crucial , with behavioural change considered important for participants in both treatments , and cognitive change unsurprisingly discussed more by those receiving CBT . Both therapies were considered to have a positive impact on symptoms of depression and other areas of life including feelings about themselves , self-care , work and relationships . Barriers to therapy included work , family life and emotional challenges . A subset ( n=2 ) of BA participants commented that therapy felt too simple , and MHWs could be perceived as inexperienced . Many participants saw therapy as a learning experience , providing them with tools to take away , with work on relapse prevention essential . Conclusions Despite barriers for some participants , BA and CBT were perceived to have many benefits , to have brought about cognitive and behavioural change and to produce improvements in many domains of participants ’ lives . To optimise the delivery of BA , inexperienced junior MHWs should be supported through good quality training and ongoing supervision . Trial registration number IS RCT N27473954 , Background : A primary goal of dialectical behaviour therapy ( DBT ) is to reduce self-harm , but findings from empirical studies are inconclusive . The aim of this study was to assess the effectiveness and cost-effectiveness of DBT in reducing self-harm in patients with personality disorder . Methods : Participants with a personality disorder and at least 5 days of self-harm in the previous year were r and omised to receive 12 months of either DBT or treatment as usual ( TAU ) . The primary outcome was the frequency of days with self-harm ; secondary outcomes included borderline personality disorder symptoms , general psychiatric symptoms , subjective quality of life , and costs of care . Results : Forty patients each were r and omised to DBT and TAU . In an intention-to-treat analysis , there was a statistically significant treatment by time interaction for self-harm ( incidence rate ratio 0.91 , 95 % CI 0.89–0.92 , p < 0.001 ) . For every 2 months spent in DBT , the risk of self-harm decreased by 9 % relative to TAU . There was no evidence of differences on any secondary outcomes . The economic analysis revealed a total cost of a mean of 5,685 GBP ( 6,786 EUR ) in DBT compared to a mean of 3,754 GBP ( 4,481 EUR ) in TAU , but the difference was not significant ( 95 % CI –603 to 4,599 GBP ) . Forty-eight per cent of patients completed DBT . They had a greater reduction in self-harm compared to dropouts ( incidence rate ratio 0.78 , 95 % CI 0.76–0.80 , p < 0.001 ) . Conclusions : DBT can be effective in reducing self-harm in patients with personality disorder , possibly incurring higher total treatment costs . The effect is stronger in those who complete treatment . Future research should explore how to improve treatment adherence A general approach is discussed to assess the uncertainty surrounding the cost effectiveness ratio ( C/E-ratio ) estimated on the basis of data from a r and omised clinical trial . The approach includes the calculation of a 95 % probability ellipse and introduces the concept of a so called C/E-acceptability curve . This last curve defines for each predefined C/E-ratio the probability that the C/E-ratio found in the study is acceptable . The approach is illustrated by estimates of costs per life saved and costs per patient discharged alive on the basis of data from a phase II trial addressing the value of anakinra in treating sepsis syndrome Ost ( 2008 ) recently compared the method ological rigor of studies of acceptance and commitment therapy ( ACT ) and traditional cognitive behavior therapy ( CBT ) . He concluded that the ACT studies had more method ological deficiencies , and thus the treatment did not qualify as an " empirically supported treatment . " Although Ost noted several important limitations that should be carefully considered when evaluating early ACT research , his attempt to devise an empirical matching strategy by creating a comparison sample of CBT studies to bolster his conclusions was itself problematic . The sample s were clearly mismatched in terms of the population s being treated , leading to differences in study design and methodology . Furthermore , re analysis showed clear differences in grant support favoring CBT compared with ACT studies that were not reported in the original article . Given the actual mismatch between the sample s , Ost 's method ological ratings are difficult to interpret and provide little useful information beyond what could already be gathered by a qualitative review of ACT study limitations . Such limitations are characteristic of the earlier r and omized controlled trials of any emerging psychotherapeutic approach Background : Mindfulness-based interventions have been shown to effectively reduce anxiety , depression and pain in patients with chronic physical illnesses . Objectives : We assessed the potential effectiveness and cost-effectiveness of a specially adapted Skype distant-delivered mindfulness intervention , design ed to reduce distress for people affected by primary and secondary progressive MS . Methods Forty participants were r and omly assigned to the eight-week intervention ( n = 19 ) or a waiting-list control group ( n = 21 ) . Participants completed st and ardised question naires to measure mood , impact of MS and symptom severity , quality of life and service costs at baseline , post-intervention and three-month follow-up . Results : Distress scores were lower in the intervention group compared with the control group at post-intervention and follow-up ( p < 0.05 ) , effect size −0.67 post-intervention and −0.97 at follow-up . Mean scores for pain , fatigue , anxiety , depression and impact of MS were reduced for the mindfulness group compared with control group at post-therapy and follow-up ; effect sizes ranged from −0.27 to −0.99 post-intervention and −0.29 to −1.12 at follow-up . There were no differences in quality -adjusted life years , but an 87.4 % probability that the intervention saves on service costs and improves outcome . Conclusions : A mindfulness intervention delivered through Skype video conferences appears accessible , feasible and potentially effective and cost-effective for people with progressive MS Objective : While mindfulness-based cognitive therapy is effective in reducing depressive relapse/recurrence , relatively little is known about its health economic properties . We describe the health economic properties of mindfulness-based cognitive therapy in relation to its impact on depressive relapse/recurrence over 2 years of follow-up . Method : Non-depressed adults with a history of three or more major depressive episodes were r and omised to mindfulness-based cognitive therapy + depressive relapse active monitoring ( n = 101 ) or control ( depressive relapse active monitoring alone ) ( n = 102 ) and followed up for 2 years . Structured self-report instruments for service use and absenteeism provided cost data items for health economic analyses . Treatment utility , expressed as disability-adjusted life years , was calculated by adjusting the number of days an individual was depressed by the relevant International Classification of Diseases 12-month severity of depression disability weight from the Global Burden of Disease 2010 . Intention-to-treat analysis assessed the incremental cost – utility ratios of the interventions across mental health care , all of health-care and whole-of-society perspectives . Per protocol and site of usual care subgroup analyses were also conducted . Probabilistic uncertainty analysis was completed using cost – utility acceptability curves . Results : Mindfulness-based cognitive therapy participants had significantly less major depressive episode days compared to controls , as supported by the differential distributions of major depressive episode days ( modelled as Poisson , p < 0.001 ) . Average major depressive episode days were consistently less in the mindfulness-based cognitive therapy group compared to controls , e.g. , 31 and 55 days , respectively . From a whole-of-society perspective , analyses of patients receiving usual care from all sectors of the health-care system demonstrated dominance ( reduced costs , demonstrable health gains ) . From a mental health-care perspective , the incremental gain per disability-adjusted life year for mindfulness-based cognitive therapy was AUD83,744 net benefit , with an overall annual cost saving of AUD143,511 for people in specialist care . Conclusion : Mindfulness-based cognitive therapy demonstrated very good health economic properties lending weight to the consideration of mindfulness-based cognitive therapy provision as a good buy within health-care delivery |
12,932 | 26,608,703 | Their clinical outcomes seem currently acceptable in general , and external flexible annuloplasty has been performed more frequently with favorable outcomes .
However , they are still performed for a minority of patients by special experienced teams with limited follow-up periods . | Annuloplasty is considered to play a key role to control aortic valve regurgitation ( AR ) and prevent recurrence of AR after aortic valve repair , because aortic root dilatation has emerged as a risk factor for recurrence of AR .
Various modifications of annuloplasty have been advocated , however , none of them has become st and ardized .
Thus in this review they are outlined and classified ( internal/external , with/without ring , rigid/flexible ring ) , and their advantages and disadvantages are clarified . | OBJECTIVE The study objective was to compare the 30-day outcomes of a st and ardized aortic valve repair technique ( REPAIR group ) associating root remodeling with an expansible aortic ring annuloplasty versus mechanical composite valve and graft ( CVG group ) replacement in treating aortic root aneurysms . METHODS A total of 261 consecutive patients with aortic root aneurysm were enrolled in this multicentric prospect i ve cohort ( 131 in the CVG group , 130 in the REPAIR group ) in 20 centers . The main end point is a composite criterion including mortality ; reoperation ; thromboembolic , hemorrhagic , or infectious events ; and heart failure . Secondary end points were major adverse valve-related events . Crude and propensity score adjusted estimates are provided . RESULTS The mean age was 56.1 years , and the valve was bicuspid in 115 patients ( 44.7 % ) . The median ( interquartile range ) preoperative aortic insufficiency grade was 2.0 ( 1.0 - 3.0 ) in the REPAIR group and 3.0 ( 2.0 - 3.0 ) in the CVG group ( P = .0002 ) . Thirty-day mortality was 3.8 % ( n = 5 ) in both groups ( P = 1.00 ) . Despite a learning curve and longer crossclamp times for valve repair ( 147.7 vs 99.8 minutes , P < .0001 ) , the 2 groups did not differ significantly for the main criterion ( odds ratio , 1.31 ; 95 % confidence interval , 0.72 - 2.40 ; P = .38 ) or 30-day mortality ( odds ratio , 0.99 ; 95 % confidence interval , 0.28 - 3053 ; P = .99 ) , with a trend toward more frequent major adverse valve-related events in the CVG group ( odds ratio , 2.52 ; 95 % confidence interval , 0.86 - 7.40 ; P = .09 ) . At discharge , 121 patients ( 96.8 % ) in the REPAIR group had grade 0 or 1 aortic insufficiency . CONCLUSIONS A new st and ardized approach to valve repair , combining an expansible aortic annuloplasty ring with the remodeling technique , presented similar 30-day results to mechanical CVG with a trend toward reducing major adverse valve-related events . Analysis of late outcomes is in process for 3- and 10-year follow-ups BACKGROUND Refining leaflet reconstruction has become a primary issue in aortic valve repair . This descriptive analysis review s leaflet pathology , repair techniques , and early results in a prospect i ve regulatory trial of aortic valve repair . METHODS Sixty-five patients underwent valve repair for predominant moderate to severe aortic insufficiency ( AI ) . The mean age was 63 ± 13 years , and 69 % of the patients were male . Ascending aortic/root replacement was required in 62 % . As a first step , ring annuloplasty was performed , and then leaflet repair included leaflet plication for prolapse , nodular unfolding , double pericardial patching of commissural defects or holes , complete pericardial leaflet replacement , leaflet extension , and Gore-Tex reinforcement . Leaflet techniques and causes of adverse outcomes were evaluated . RESULTS The follow-up time was 2-years maximal and 0.9 years mean , with a survival of 97 % . Eighty percent of patients required repair of leaflet defects : leaflet prolapse ( 52/65 - 80 % ) , ruptured commissures ( 6/65 - 9 % ) , leaflet holes ( 4/65 - 6 % ) , and nodular retraction ( 6/65 - 9 % ) . The average preoperative AI grade of 2.9 ± 0.8 fell to 0.7 ± 0.7 ( p < 0.0001 ) . Three patients ( 4.6 % ) required interval valve replacement because of ( 1 ) suture untying , ( 2 ) iatrogenic leaflet tear , or ( 3 ) diphtheroid endocarditis . Five other patients experienced grade 2 or grade 3 AI : probable suture untying in 1 patient , ineffective leaflet extensions in 2 patients , and unsuccessful Gore-Tex reinforcements in 2 patients . Two patients with single pericardial leaflet replacements and all those with double pericardial reconstructions did well . CONCLUSIONS Leaflet defects are common in patients with moderate to severe AI . Leaflet plication , nodular unfolding , and double pericardial patching performed well . Gore-Tex and leaflet extension seemed less satisfactory . St and ardization and experience with leaflet reconstruction will be important for optimizing the outcomes of aortic valve repair Comprehensive aortic root and valve repair ( CARVAR ) is a recently introduced surgical technique for aortic valve disease . The National Evidence -based Health Care Collaborating Agency was offered by the ministry of Health and Welfare , Korea to perform a restrospective outcome analysis for this surgical procedure . The aims of this study were to evaluate the safety of patients who underwent CARVAR surgery and to provide a rationale for further prospect i ve r and omized study . During the period of March 2007 to November 2009 , 397 patients received this procedure and enrolled in this study . Clinical events including major bleeding , endocarditis , re-operation and death were followed-up till March 2010 by medical records . During the follow-up periods , 1-year cumulative incidence of major bleeding , re-operation , endocarditis and death were 3.55 , 5.65 , 5.05 and 5.33%/year respectively . This study showed that the CARVAR technique is not beneficial , and is indeed even more harmful than conventional valve replacement surgery OBJECTIVES A geometric annuloplasty ring could improve efficacy and stability of aortic valve repair . Toward this goal , a 1-piece 3-dimensional titanium annuloplasty ring with Dacron covering was developed and tested successfully in animals . The purpose of this study was to define hemodynamic outcomes with this device used as the annuloplasty component of human aortic valve repair . METHODS In a 4-center pilot trial with informed consent , 16 patients underwent aortic valve repair for aortic insufficiency , with the annuloplasty device sutured into the annulus beneath the leaflets . Preoperative annular diameter averaged 26.5 ± 2.0 ( mean ± st and ard deviation ) mm , and average ring size was 22.3 ± 1.2 mm . After annuloplasty , leaflet defects were easy to identify , and 14 of 16 patients ( 88 % ) required leaflet plication and /or autologous pericardial reconstruction for leaflet defects . Three patients had ascending aortic replacement , and 2 had remodeling root replacement . One had ultrasonic leaflet decalcification and another tricuspid valve annuloplasty . Follow-up data were from site-specific studies at the 6-month postoperative time point . RESULTS There were no in-hospital mortalities or major complications . Preoperative aortic insufficiency grade ( 0 - 4 scale ) was 3.6 ± 1.0 and fell to 1.0 ± 0.8 at 6 months ( P < .0001 ) . New York Heart Association class fell from 2.5 ± 0.5 to 1.1 ± 0.3 ( P < .0001 ) . Postrepair valve area was 2.7 ± 0.2 cm(2 ) , and 6-month mean systolic gradient was 11.3 ± 3.3 mm Hg . Left ventricular end-diastolic diameter and ejection fraction both normalized ( both P < .0001 ) . CONCLUSIONS Geometric ring annuloplasty facilitated aortic valve repair , allowing more precise reconstruction of leaflet defects . Aortic insufficiency reduction and systolic gradients were excellent , and expansion of valve reconstruction into broader categories of aortic valve disease seems indicated |
12,933 | 26,215,198 | Conclusions A practical approach to performance improvement was used by the American Society of Breast Surgeons to create a toolbox of options to reduce lumpectomy reoperations and improve cosmetic outcomes | Background Multiple recent reports have documented significant variability of reoperation rates after initial lumpectomy for breast cancer .
To address this issue , a multidisciplinary consensus conference was convened during the American Society of Breast Surgeons 2015 annual meeting .
Methods The conference mission statement was to “ reduce the national reoperation rate in patients undergoing breast conserving surgery for cancer , without increasing mastectomy rates or adversely affecting cosmetic outcome , thereby improving value of care . ”
The goal was to develop a toolbox of recommendations to reduce the variability of reoperation rates and improve cosmetic outcomes . | With the increasing use of magnetic resonance imaging ( MRI ) , the physician is more frequently confronted with nonpalpable breast lesions that are only visible on MRI . In these cases , it is often difficult to obtain adequate material for pathological examination . One of the methods that may be performed is excisional biopsy after MRI-guided wire localization . This study intends to examine the feasibility and added benefit of this method . It appears to be a reliable and useful tool that is , therefore , of additional benefit to surgical practice Background Few published studies have shown the benefits of intraoperative ultrasound in avoiding inadequate margins in breast-conserving surgery . The aim of this study is to quantify intraoperative ultrasound margin size and assess its relationship to tumor size , multifocality , palpability , histology , and presence of intraductal component . Methods Patients with breast cancer undergoing breast-conserving surgery in whom the operating surgeon visualized the tumor by ultrasound were included . Ultrasound margins measured intraoperatively were prospect ively recorded and compared with pathology margins . Results Forty-five patients with 48 tumors were included . Twenty five patients ( 56 % ) had palpable tumors . Pathologic mean tumor size was 1.9 cm [ 95 % confidence interval ( CI ) 1.6–2.2 cm , range 0.5–4.8 cm ] . There was good correlation between closest margins recorded by ultrasound and pathology margins ( r = 0.4674 , P < 0.0008 ) . Fourteen patients ( 31 % ) had margins re-excised intraoperatively , 12 of them in the direction of the closest pathological margin . Three patients ( 7 % ) , all of whom had intraoperative re-excision , had a second operation for involved margins without residual cancer on pathological examination of the reoperative specimens . Ultrasound margins ≥0.5 cm achieved adequate pathology margins of ≥0.2 cm in 95 % of margins . Overestimation of pathology margins by ultrasound measurement was significantly affected by multifocality ( P = 0.0473 ) . Tumor size , palpability , invasive lobular histology , and presence of ductal carcinoma in situ ( DCIS ) did not cause significant overestimation of pathology margins by ultrasound . Conclusions Intraoperative ultrasound may help maintain a low level of reoperation after breast-conserving surgery . Ultrasound margins < 0.5 cm should be re-excised intraoperatively . Reliability of ultrasound in predicting the closest pathology margins was diminished in patients with multifocal tumors Abstract Background : Wire localization ( WL ) is the current st and ard for surgical diagnosis of nonpalpable breast lesions . Many disadvantages inherent to WL are solved with radioactive seed localization ( RSL ) . This trial investigated the ability of RSL to reduce the need for specimen radiographs and operating room delays associated with WL . Methods : A total of 134 women were entered onto an institutional review board – approved study . RSL was performed by placing a titanium seed containing .29 to 20 mCi of iodine-125 to within 1 cm of the suggestive breast lesion . The surgeon used a h and held gamma detector to locate and excise the iodine-125 seed and the lesion . Results : Specimen radiographs were eliminated in 98 ( 79 % ) of 124 patients . Surgical seed retrieval was 100 % in 124 patients . No seed migration occurred after correct radiographical placement . A total of 26 ( 21 % ) of 124 patients required a specimen radiograph ; 22 ( 85 % ) of these 26 were performed for microcalcifications . Conclusions : After surgical removal , RSL can eliminate specimen radiographs when the radiologist accurately places the seed and the pathologist grossly identifies the lesion . If small microcalcifications are noted before surgery , then specimen radiographs may be necessary . RSL reduced requirements for specimen radiographs , decreased OR time , improved incision placement , and improved resections to clear margins Background The wire-guided excision of nonpalpable breast cancer often results in tumor resections with inadequate margins . This prospect i ve , r and omized trial was undertaken to investigate whether intraoperative ultrasound ( US ) guidance enables a better margin clearance than the wire-guided technique in the breast-conserving treatment of nonpalpable breast cancers . Methods Patients with a preoperative histological diagnosis of nonpalpable breast cancer that could be visualized both with US and mammography were included . Patients were r and omized to undergo either a wire-guided or a US-guided excision . Adequate margins were defined as ≥1 mm . Results Of 49 included patients , 23 were assigned to undergo wire-guided excision and 26 to undergo US-guided excision . One patient crossed over to US-guided excision after inadvertent wire displacement . Mean tumor diameter , specimen weight , and operating time were similar in both groups . The excision was adequate in 24 ( 89 % ) of 27 US-guided excisions and 12 ( 55 % ) of 22 wire-guide excisions ( P=.007 ) . Conclusions US-guided excision seems to be superior to wire-guided excision with respect to margin clearance of mammographically detected and US-visible nonpalpable breast cancers . Patients do not have to undergo the unpleasant wire placement before surgery BACKGROUND Routine resection of cavity shave margins ( additional tissue circumferentially around the cavity left by partial mastectomy ) may reduce the rates of positive margins ( margins positive for tumor ) and reexcision among patients undergoing partial mastectomy for breast cancer . METHODS In this r and omized , controlled trial , we assigned , in a 1:1 ratio , 235 patients with breast cancer of stage 0 to III who were undergoing partial mastectomy , with or without resection of selective margins , to have further cavity shave margins resected ( shave group ) or not to have further cavity shave margins resected ( no-shave group ) . R and omization occurred intraoperatively after surgeons had completed st and ard partial mastectomy . Positive margins were defined as tumor touching the edge of the specimen that was removed in the case of invasive cancer and tumor that was within 1 mm of the edge of the specimen removed in the case of ductal carcinoma in situ . The rate of positive margins was the primary outcome measure ; secondary outcome measures included cosmesis and the volume of tissue resected . RESULTS The median age of the patients was 61 years ( range , 33 to 94 ) . On final pathological testing , 54 patients ( 23 % ) had invasive cancer , 45 ( 19 % ) had ductal carcinoma in situ , and 125 ( 53 % ) had both ; 11 patients had no further disease . The median size of the tumor in the greatest diameter was 1.1 cm ( range , 0 to 6.5 ) in patients with invasive carcinoma and 1.0 cm ( range , 0 to 9.3 ) in patients with ductal carcinoma in situ . Groups were well matched at baseline with respect to demographic and clinicopathological characteristics . The rate of positive margins after partial mastectomy ( before r and omization ) was similar in the shave group and the no-shave group ( 36 % and 34 % , respectively ; P=0.69 ) . After r and omization , patients in the shave group had a significantly lower rate of positive margins than did those in the no-shave group ( 19 % vs. 34 % , P=0.01 ) , as well as a lower rate of second surgery for margin clearance ( 10 % vs. 21 % , P=0.02 ) . There was no significant difference in complications between the two groups . CONCLUSIONS Cavity shaving halved the rates of positive margins and reexcision among patients with partial mastectomy . ( Funded by the Yale Cancer Center ; Clinical Trials.gov number , NCT01452399 . ) The role of cavity shaves in reducing re-excision rates in breast conserving surgery ( BCS ) remains unclear . We compared rates of close margins and re-excision following cavity shaves based on either intraoperative radiology or systematic cavity shaves . Data was recorded prospect ively from 1999 to 2003 for 217 patients undergoing BCS . For the first 106 cases , cavity shaves were performed when intraoperative radiological margins appeared close ( < 10 mm ) . The remaining 111 cases had systematic superior and inferior cavity shaves ( SSICS ) . Close margins and re-excision rates were compared between groups . The median weight of excised tissue was less in group two : 82.8 g versus 100.5 g , P=0.001 . SSICS reduced close margins by 83 % ( 18/106 versus 8/111 ) , OR 0.17 , 95 % CI 0.08 - 0.48 , P=0.001 . Multivariate analysis showed SSICS also reduced re-excision rates ( 15 versus 8 cases ) , OR 0.26 , 95 % CI 0.09 - 0.74 , P=0.012 . SSICS reduces close margins and re-excision rates . This approach has additional cosmetic benefits because less tissue is excised Background Studies suggest radioguided seed localization ( RSL ) yields fewer positive margins than wire-guided localization ( WL ) . The goal of this study is to determine whether RSL is superior to WL . Methods Women with confirmed invasive or ductal carcinoma in situ ( DCIS ) undergoing localization and breast conserving surgery were enrolled . Outcomes measured include positive margin and reoperation rates , specimen weight , operative and localization times , and surgeon and radiologist ranking of procedural difficulty . Results R and omization was central ized , concealed , and stratified by surgeon with 153 patients in the WL group and 152 in RSL group . Localizations were performed using either ultrasound ( 70 % ) or mammographic guidance ( 30 % ) . Pathology was either DCIS ( 18 % ) or invasive carcinoma ( 82 % ) . Procedures were performed at 3 sites , by 7 surgeons . Only difference found for patient and tumor characteristics was more multifocal disease in RSL group . Using intention-to-treat analysis , there were no differences in positive margins rates for RSL ( 10.5 % ) and WL ( 11.8 % ) , ( P = .99 ) or for positive or close margins ( < 1 mm ) ( RSL 19 % and WL 22 % ; P = .61 ) . Mean operative time ( minutes ) was shorter for RSL ( RSL 19.4 vs WL 22.2 ; P < .001 ) . Specimen volume , weight , reoperation and localization times were similar . Surgeons ranked the seed technique as easier ( P = .008 ) , while radiologists ranked them similarly . Patient ’s pain rankings during wire localization were higher ( P = .038 ) . Conclusions In contrast to other trials positive margin and reoperation rates were similar for RSL and WL . However , for RSL operative times were shorter , and the technique was preferred by surgeons , making it an acceptable method for localization Objective : To develop an intraoperative method for margin status evaluation during breast conservation therapy ( BCT ) using an automated analysis of imprint cytology specimens . Study Design : Imprint cytology sample s were prospect ively taken from 47 patients undergoing either BCT or breast reduction surgery . Touch preparations from BCT patients were taken on cut sections through the tumor to generate positive margin controls . For breast reduction patients , slide imprints were taken at cuts through the center of excised tissue . Analysis results from the presented technique were compared against st and ard pathologic diagnosis . Slides were stained with cytokeratin and Hoechst , imaged with an automated fluorescent microscope , and analyzed with a fast algorithm to automate discrimination between epithelial cells and noncellular debris . Results : The accuracy of the automated analysis was 95 % for identifying invasive cancers compared against final pathologic diagnosis . The overall sensitivity was 87 % while specificity was 100 % ( no false positives ) . This is comparable to the best reported results from manual examination of intraoperative imprint cytology slides while reducing the need for direct input from a cytopathologist . Conclusion : This work demonstrates a proof of concept for developing a highly accurate and automated system for the intraoperative evaluation of margin status to guide surgical decisions and lower positive margin rates Lumpectomy specimens are commonly divided into six sides : superficial , deep , superior , inferior , medial , and lateral . Orienting stitches are placed on the specimen during surgery to allow reorientation by pathology . Despite those efforts , specimen disorientation may occur . The aim of this study was to assess the correlation in orientation between surgeons and pathologists . Lumpectomy specimens were routinely oriented . An additional Prolene suture was r and omly placed by the surgeon on one side to be localized by pathology . The results were recorded and the disorientation rate calculated . Specimen size and presence of skin and /or muscle were also recorded . There were 122 lumpectomy specimens prospect ively entered . Average specimen volume was 95.5 cm3 . Twenty-four specimens had segments of skin or muscle . The additional sutures were evenly divided between the six sides . The overall disorientation rate was 31.1 % ( 95 % confidence interval , 23.1–40.2).The side-specific disorientation rates were 43 % , 40 % , 35 % , 29 % , 28 % , and 14 % for the deep , superficial , lateral , medial , superior , and inferior surfaces , respectively ( no statistical difference ) . Presence of skin or muscle on the specimen did not contribute to better orientation . Specimen volumes , however , were highly associated with orientation . Specimens of < 20 cm3 had a disorientation rate of 78 % , while larger specimen had a disorientation rate of 20 % ( p < .001 ) . Specimen orientation with stitches placed on two surfaces is associated with a high disorientation rate . Better orientation techniques are necessary to minimize the specimen disorientation Introduction : Oncoplastic reconstructive surgery is performed in select patients with breast cancer to allow conservation treatment when the lumpectomy would be expected to have a poor cosmetic outcome . These techniques not only rearrange the breast tissue but may also shift the position of the tumor bed . The oncoplastic incision may have no relationship to the tumor bed . Although use of whole-breast radiation therapy ( RT ) is straightforward , difficulties in localization of the tumor bed for the local RT boost have not been investigated . Material s and Methods : A retrospective review was performed of 25 patients with 26 cancers who received RT after breast conservation surgery with oncoplastic reconstruction . Results : Among 11 patients with a minimum of 4 surgical clips placed at tumor resection , 8 ( 73 % ) had the final tumor bed extend beyond the original breast quadrant or be completely relocated into a different region . In 3 ( 27 % ) cases , the clinical treatment volume was 2 to 3 separated regions within the breast . Discussion : For breast cancer patients who have had oncoplastic surgery , the tumor bed is frequently more extensive and possibly relocated compared with original presentation . Placement of surgical clips after tumor resection and before oncoplastic reconstruction may be the most accurate method to localize the RT local boost field INTRODUCTION Non-palpable breast tumors represent an increasing management problem in modern Breast Units . Therefore , a simple and accurate procedure to localize these lesions is needed . To date , the most commonly used technique is wire localization , but there are some disadvantages . METHODS We conducted a prospect i ve study on patients with malignant or benign non-palpable breast tumors who were surgically treated and underwent intraoperative ultrasound ( IOUS ) from May 2006 to June 2007 . Margins of excision were inked and specifically assessed by the pathologist , and were considered positive if < or=1 mm . RESULTS There were 77 patients ( 60 malignant and 17 benign lesions ) , with a median age of 54 years ( 36 - 87 ) , and a median diameter of 9 mm ( 4 - 17 ) . All lesions were correctly identified and localized by IOUS , and free margins of excision were obtained in 75/77 cases ( 97 % ) . Only two patients required a re-excision , one for multifocal disease and one for margins of excision of 1 mm . In the remaining cases , the median distance from the tumor to the closest margins of excision , with exclusion of the posterior ( fascial ) and anterior ( skin ) margins , was 1.3 cm ( 0.3 - 3.2 ) . CONCLUSIONS IOUS is a simple and accurate procedure that can be used to identify most non-palpable breast tumors , and has many advantages over the more commonly used wire-localization technique Abstract Background The presence of tumor cells at the margins of breast lumpectomy specimens is associated with an increased risk of ipsilateral tumor recurrence . Twenty to 30 % of patients undergoing breast-conserving surgery require second procedures to achieve negative margins . This study evaluated the adjunctive use of the MarginProbe device ( Dune Medical Devices Ltd , Caesarea , Israel ) in providing real-time intraoperative assessment of lumpectomy margins . Methods This multicenter r and omized trial enrolled patients with nonpalpable breast malignancies . The study evaluated MarginProbe use in addition to st and ard intraoperative methods for margin assessment . After specimen removal and inspection , patients were r and omized to device or control arms . In the device arm , MarginProbe was used to examine the main lumpectomy specimens and direct additional excision of positive margins . Intraoperative imaging was used in both arms ; no intraoperative pathology assessment was permitted . Results In total , 596 patients were enrolled . False-negative rates were 24.8 and 66.1 % and false-positive rates were 53.6 and 16.6 % in the device and control arms , respectively . All positive margins on positive main specimens were resected in 62 % ( 101 of 163 ) of cases in the device arm , versus 22 % ( 33 of 147 ) in the control arm ( p < 0.001 ) . A total of 19.8 % ( 59 of 298 ) of patients in the device arm underwent a reexcision procedure compared with 25.8 % ( 77 of 298 ) in the control arm ( 6 % absolute , 23 % relative reduction ) . The difference in tissue volume removed was not significant . Conclusions Adjunctive use of the MarginProbe device during breast-conserving surgery improved surgeons ’ ability to identify and resect positive lumpectomy margins in the absence of intraoperative pathology assessment , reducing the number of patients requiring reexcision . MarginProbe may aid performance of breast-conserving surgery by reducing the burden of reexcision procedures for patients and the health care system Background Mammogram-directed wire localization for nonpalpable cancer requires surgeon ’s time and coordination and some patient discomfort . Up to half of these nonpalpable lesions can be visualized by ultrasound . Use of intraoperative ultrasound streamlines the process of image-guided surgery . Methods We prospect ively visualized 69 nonpalpable breast cancers between January 1998 and July 2001 . Ultrasound localization was performed in the operating room immediately before definitive surgery . Breast cancers were localized using either blue dye or a guide wire . Results Ultrasound correctly localized all lesions at surgery . Negative margins for invasive carcinoma were found in 97 % ( 67 of 69 ) of patients . Re-excisions were performed in only 6 % ( 4 of 69 ) of patients . Overall negative margins were found in 90 % ( 62 of 69 ) of patients . Most positive margins ( 71 % ) were due to the presence of noncalcified ductal carcinoma in situ . Mastectomy was necessary in 4 % of patients , usually due to multifocal invasive carcinoma . Conclusions Increased familiarity with ultrasound has allowed the surgeon to localize breast cancer in the operating room , improving the process of image-guided surgery . Ultrasound localization is accurate , time efficient , technically feasible , and easier for the patient . The re-excision rate is very low and is similar to that for mammographic localization . Intraoperative ultrasound localization should be considered whenever a breast cancer needs image-guided excision Intraoperative ultrasound ( IOUS ) can be used in the operation theatre for localization of non-palpable breast cancers . In this prospect i ve cohort study , we compared the yield of IOUS to guidewire localization ( GWL ) . A total of 258 consecutive patients with non-palpable invasive breast cancer underwent breast conserving surgery between 1999 and 2010 . GWL was performed in 138 ( 54 % ) and IOUS in 120 ( 46 % ) patients . Tumor dimensions , resection volume , margin status and re-excision rates were compared by means of multivariate regression analysis . The groups were similar in terms of age , histological subtype and presence of DCIS . Lesions in the IOUS group were larger ( 1.24 vs. 0.98 cm , P < 0.001 ) , while microcalcifications were more common in the GWL group ( 19 vs. 3 % , P < 0.001 ) . Even after stratification for tumor diameter , presence of DCIS and findings on mammography , resection volumes were similar in both groups . Tumor-free resection margins were obtained in > 93 % of patients ( 93.5 % with GWL vs. 93.3 % with IOUS , P = 0.958 ) and re-excision was performed in 11 % of patients undergoing GWL and 12.5 % of patients undergoing IOUS ( P = 0.684 ) . For localization of non-palpable breast cancer , IOUS is a reliable alternative to GWL , as it achieves similar results in terms of complete tumor removal , re-excision rate and excised volume Background Accurate preoperative localization of nonpalpable breast cancer is essential to achieve complete resection . Radioguided occult lesion localization ( ROLL ) has been introduced as an alternative for wire-guided localization ( WGL ) . Although efficacy of ROLL has been established in a r and omized controlled trial , cost-effectiveness of ROLL compared with WGL is not yet known . The objective of this study was to determine whether ROLL has acceptable cost-effectiveness compared with WGL . Methods An economic evaluation was performed along with a r and omized controlled trial ( Clinical Trials.gov , No. NCT00539474 ) . Women ( > 18 years ) with histologically proven nonpalpable breast cancer and eligible for breast conserving treatment with sentinel node procedure were r and omized to ROLL ( n = 162 ) or WGL ( n = 152 ) . Empirical data on direct medical costs were collected , and changes in quality of life were measured over a 6-month period . Bootstrapping was used to assess uncertainty in cost-effectiveness estimates , and sensitivity of the results to the missing data approach was investigated . Results In total , 314 patients with 316 invasive breast cancers were enrolled . On average ROLL required the same time as WGL for the surgical procedure ( 119 vs 118 min ) , result ed in a 7 % higher re interventions risk , and 13 % more complications . Quality of life effects were similar ( difference 0.00 QALYs 95 % CI ( −0.04–0.05 ) . Total costs were also similar for ROLL and WGL ( + € 26 per patient 95 % CI € −250–311 ) . Conclusion ROLL is comparable to WGL with respect to both costs and quality of life effects as measured with the EQ5D and will therefore not lead to more cost-effective medical care BACKGROUND It is important to optimize the localization technique for non-palpable breast lesions . METHODS One hundred consecutive women with non-palpable breast lesions were r and omized to radioguided occult lesion localization ( ROLL ) or wire localization ( WL ) . For ROLL technique (99m)Tc-labeled particles of human serum albumin were injected under breast-imaging control . Localization of the lesion was done in the operating room with the aid of a gamma-probe . All lesions were identified in an X-ray control of the surgical specimen . Categorical variables were analyzed with the Chi-square method . Significance was considered at P < 0.05 . RESULTS All procedures were performed on the same day of excision , on ambulatory basis . Both techniques result ed in 100 % retrieval of the lesions . Localization time was reduced with ROLL ( P < 0.001 ) . Clear margins were achieved in 88.9 % ROLLs and 62.5 % WLs ( P < 0.05 ) reducing the requirement of re-excision . There were significant differences in the subjective ease of the procedures in favor of ROLL technique as rated by surgeons and radiologists . CONCLUSIONS ROLL technique is as effective as WL for excision of non-palpable breast lesions , reduce localization time and probably the incidence of pathologically involved margins of excision . ROLL appears to improve the learning curve for surgical residents and cosmesis . ROLL is an attractive alternative to WL BACKGROUND Despite recent developments in preoperative breast cancer imaging , intraoperative localization of tumor tissue can be challenging , result ing in tumor-positive resection margins during breast conserving surgery . Based on certain physicochemical similarities between Technetium((99m)Tc)-sestamibi ( MIBI ) , an SPECT radiodiagnostic with a sensitivity of 83 - 90 % to detect breast cancer preoperatively , and the near-infrared ( NIR ) fluorophore Methylene Blue ( MB ) , we hypothesized that MB might detect breast cancer intraoperatively using NIR fluorescence imaging . METHODS Twenty-four patients with breast cancer , planned for surgical resection , were included . Patients were divided in 2 administration groups , which differed with respect to the timing of MB administration . N = 12 patients per group were administered 1.0 mg/kg MB intravenously either immediately or 3 h before surgery . The mini-FLARE imaging system was used to identify the NIR fluorescent signal during surgery and on post-resected specimens transferred to the pathology department . Results were confirmed by NIR fluorescence microscopy . RESULTS 20/24 ( 83 % ) of breast tumors ( carcinoma in N = 21 and ductal carcinoma in situ in N = 3 ) were identified in the resected specimen using NIR fluorescence imaging . Patients with non-detectable tumors were significantly older . No significant relation to receptor status or tumor grade was seen . Overall tumor-to- background ratio ( TBR ) was 2.4 ± 0.8 . There was no significant difference between TBR and background signal between administration groups . In 2/4 patients with positive resection margins , breast cancer tissue identified in the wound bed during surgery would have changed surgical management . Histology confirmed the concordance of fluorescence signal and tumor tissue . CONCLUSIONS This feasibility study demonstrated an overall breast cancer identification rate using MB of 83 % , with real-time intraoperative guidance having the potential to alter patient management Introduction Measuring and improving quality of care is of primary interest to patients , clinicians , and payers . The National Consortium of Breast Centers ( NCBC ) has created a unique program to assess and compare the quality of interdisciplinary breast care provided by breast centers across the country . Methods In 2005 the NCBC Quality Initiative Committee formulated their initial series of 37 measurements of breast center quality , eventually called the National Quality Measures for Breast Centers ( NQMBC ) . Measures were derived from published literature as well as expert opinion . An interactive website was created to enter measurement data from individual breast centers and to provide customized comparison reports . Breast centers su bmi t information using data they collect over a single month on consecutive patients . Centers can compare their results with centers of similar size and demographic or compare themselves to all centers who supplied answers for individual measures . New data may be su bmi tted twice yearly . Serially su bmi tted data allow centers to compare themselves over time . NQMBC r and om audits confirm accuracy of su bmi tted data . Early results on several initial measures are reported here . Results Over 200 centers are currently su bmi tting data to the NQMBC via the Internet without charge . These measures provide insight regarding timeliness of care provided by radiologists , surgeons , and pathologists . Results are expressed as the mean average , as well as 25th , 50th , and 75th percentiles for each metric . This sample of seven measures includes data from over 30,000 patients since 2005 , representing a powerful data base . In addition , comparison results are available every 6 months , recognizing that benchmarks may change over time . Conclusions A real-time web-based quality improvement program facilitates breast center input , providing immediate comparisons with other centers and results serially over time . Data may be used by centers to recognize high- quality care they provide or to identify areas for quality improvement . Initial results demonstrate the power and potential of web-based tools for data collection and analysis from hundreds of centers who care for thous and s of patients Abstract Backround : Breast conservation therapy is controversial for ductal carcinoma in situ ( DCIS ) due to recently reported high recurrence rates . We believe that cytologic evaluation of lumpectomy margins improves efficiency and leads to a lower recurrence rate following lumpectomy for DCIS . Methods : A prospect ively accrued data base of 1255 breast cancer patients at the H. Lee Moffitt Cancer Center and Research Institute was found to have 218 patients with DCIS ( 17.4 % ) . Of those 218 cases , 114 were treated with lumpectomy , axillary dissection , and radiation therapy ; the remaining 104 patients were treated with mastectomy with or without reconstruction . Imprint cytology was used to evaluate all lumpectomy margins . Permanent sections and imprint cytology were review ed by the same pathologist . Results : All lumpectomy specimens ( 116 tumors in 114 patients ) were evaluated . The median follow up was 57.5 months ( range 2–110 months ) . One hundred and three patients with 104 tumors were selected on the basis of pure DCIS ( with or without microinvasion ) , and treated with lumpectomy , axillary dissection and radiation therapy . Of the 104 tumors utilizing attempted breast conservation therapy , 7 ( 6.6 % ) required mastectomy . There were 6 recurrences ( 6.1 % ) with a median time for recurrence of 47.5 months ( range 27–85 months ) ; four recurrences were comedo and two were noncomedo at original diagnosis . Conclusions : The determination of lumpectomy margins in DCIS patients using imprint cytology leads to an overall recurrence rate of 6.1 % with reduction in operative time , and re-excision rate . Significant recurrence rates were associated with microinvasion and multifocal tumors ( 28 % ) versus simple DCIS at 5 years . Breast conservation therapy and surgical margin determination with imprint cytology for DCIS is a cost-effective and reliable method of treatment for simple DCIS AIMS To evaluate the patients ' satisfaction with breast reconstruction using the autologous latissimus dorsi technique and the impact of the procedure on the quality of life and body image of women who had mastectomy for breast cancer . METHODS A retrospective transversal study was conducted at the Georges François Leclerc Cancer Care Center in Dijon , France . From 1990 to 2008 , 193 women underwent reconstruction ( RW ) , among these , 141 were matched for age at diagnosis and the date of the mastectomy with women who did not undergo reconstruction ( NRW ) identified using data from the Côte d'Or breast cancer registry . Question naires concerning quality of life , body image and satisfaction ( MBROS-S , MBROS-BI , EORTC QLQ-C30 , EORTC QLQ-BR23 ) were sent through the post following surgery . RESULTS The overall response rate was 77 % and the mean ( MBROS-S ) satisfaction score was 3.36 . The quality of life ( EORTC QLQ-C30 , EORTC QLQ-BR23 ) in RW was no better than that in NRW , but body image was better ( p = 0.0247 ) especially before 60 years ( p = 0.0192 ) , in obese patients ( p = 0.03 ) and when the breasts of RW were heavy ( p = 0.0197 ) . Moreover , when the time from the mastectomy was less than 4 years , body image ( p = 0.0008 ) and the sexual activity score ( p = 0.0078 ) were higher in RW . CONCLUSIONS The level of satisfaction was higher in RW , and breast reconstruction made a strong contribution in terms of improvement in body image . A prospect i ve study to evaluate quality of life in the long term is now necessary As breast cancer screening rates increase , smaller and more numerous lesions are being identified earlier , leading to more breast-conserving surgical procedures . Achieving a clean surgical margin represents a technical challenge with important clinical implication s. Optical coherence tomography ( OCT ) is introduced as an intraoperative high-resolution imaging technique that assesses surgical breast tumor margins by providing real-time microscopic images up to 2 mm beneath the tissue surface . In a study of 37 patients split between training and study groups , OCT images covering 1 cm(2 ) regions were acquired from surgical margins of lumpectomy specimens , registered with ink , and correlated with corresponding histologic sections . A 17-patient training set used to establish st and ard imaging protocol s and OCT evaluation criteria showed that areas of higher scattering tissue with a heterogeneous pattern were indicative of tumor cells and tumor tissue in contrast to lower scattering adipocytes found in normal breast tissue . The remaining 20 patients were enrolled into the feasibility study . Of these lumpectomy specimens , 11 were identified with a positive or close surgical margin and 9 were identified with a negative margin under OCT . Based on histologic findings , 9 true positives , 9 true negatives , 2 false positives , and 0 false negatives were found , yielding a sensitivity of 100 % and specificity of 82 % . These results show the potential of OCT as a real-time method for intraoperative margin assessment in breast-conserving surgeries The ultimate goal of breast conserving surgery ( BCS ) is to achieve survival and local control rates similar to those for mastectomy while providing improved cosmetic and functional results . The volume of breast tissue removed is the most significant determinant of the final cosmetic outcome of BCS . We hypothesised that intra-operative specimen radiograph ( IOSR ) during BCS may guide the surgeon to achieve clear radiographic and histological margins with minimum normal breast tissue excision , thus preserving cosmetic appearance . The aim of this study was to evaluate the effect of introducing the policy of IOSR on the weight of specimens of wide local excision of palpable invasive breast cancer . All consecutive patients who underwent therapeutic wide local excision for palpable invasive breast cancer from 01/01/02 to 31/03/03 were included in this study . A policy of IOSR was introduced in October 2002 , thus all BCS done after 01/10/2002 underwent IOSR . The mean ( S.D. ) specimen weight for the no intra-operative specimen radiograph ( NIOSR ) group was 74 grams compared to 46 g in the IOSR group , ( P = 0.0241 , unpaired t-test with Welch 's correction ) and the mean tumour size for the NIOSR was 23(13)mm and for IOSR was 21(8)mm ( P = ns , unpaired t-test with Welch 's correction ) . A histologically clear circumferential margin rate in the IOSR group was 96 % compared to 82 % in the NIOSR group . Five patients in the IOSR group and 11 in NIOSR group had positive anterior or posterior margin . For these patients no further surgical excision was possible as BCS was performed from skin to pectoral fascia . Therefore a radiation boost was given to the site of excision . Only one patient in the IOSR group needed further breast surgery ( mastectomy ) for a positive inferior ( toward nipple ) margin for a mammographically occult tumour , while 11 patients in the NIOSR group required further breast surgery . In conclusion , IOSR is a simple , effective and economical way of assessing adequacy of margins while minimising the breast tissue excised during wide local excision of palpable breast cancers Objective Breast carcinoma is the most frequently diagnosed malignancy in women of North America . The combination of breast conservation surgery and radiotherapy has become a st and ard of treatment for the majority of breast cancers . It is critical to obtain clear margins to minimize local recurrence . However , avoiding multiple re-excisions for margin clearance helps optimize cosmetic results in patients undergoing breast conservation surgery . Intra-operative touch preparation cytology ( IOTPC ) may decrease the need for multiple re-excisions and thereby improve cosmesis . The literature suggests that IOTPC can be useful in evaluation of margins . Klimberg et al. evaluated the touch preparation technique prospect ively in 428 patients undergoing breast biopsy for undiagnosed breast masses . Margin evaluation was correct in 100 % of the lesions and was used to re-excise the margins when touch prep results were positive . They reported a diagnostic accuracy , sensitivity , specificity , positive predictive value , and negative predictive value of 100 % for the touch prep technique . To the best of our knowledge , there has been no published data on the role of IOTPC for evaluation of margins in re-excision cases . This report describes our experience with IOTPC for margin assessment for re-excision partial mastectomy at Beth Israel Medical Center ( BIMC ) . The purpose of this study is to determine whether IOTPC is reliable for evaluating margins in patients undergoing re-excision for involved or close margins . Methods A prospect i ve study of 30 patients , who have undergone re-excision partial mastectomy for involved or close margins after breast conservation surgery with the use of IOTPC for margin assessment at BIMC was performed . The re-excision lumpectomy specimens were oriented by the surgeon intra-operatively and were su bmi tted fresh to pathology for cytologic assessment . The touch prep method consisted of touching the corresponding margin onto the glass slide . The principle of this technique is that if cancer cells are present they will stick to the slide , while fat cells will not . A slide was prepared for each re-excision specimen . Air-dried sample s were stained immediately using the Diff-Quik method and examined under the microscope by a cytopathologist . Results Thirty patients underwent re-excision lumpectomy for involved or close margins with touch preparation cytology for assessment of 68 margins . Twenty-six patients had invasive ductal carcinoma and /or ductal carcinoma in situ , three patients had invasive lobular carcinoma and the remaining one patient had a combination of invasive lobular and ductal carcinoma . There was a correlation between touch prep cytology and final pathology in 56/68 margins , which accounts for 82.4 % of the cases . Conclusion Intra-operative touch preparation cytology for assessment of margins in patients undergoing re-excision lumpectomy for involved or close margins has a sensitivity of 75 % , specificity of 82.8 % , positive predictive value of 21.4 % , and negative predictive value of 98.2 % . This high negative predictive value and a single false negative margin are quite significant . Therefore , based on our experience , IOTPC can be a useful tool for intra-operative assessment of margins for patients undergoing re-excision partial mastectomy PURPOSE Experience and practice setting vary greatly among surgeons who treat breast cancer patients . However , less is known about how these factors influence patient satisfaction with their care . PATIENTS AND METHODS We surveyed all ductal carcinoma in situ patients and a 20 % r and om sample of invasive breast cancer patients diagnosed in 2002 reported to the Detroit , MI , and Los Angeles , CA , Surveillance , Epidemiology , and End Results registries . Attending surgeons were surveyed , yielding dyad information for 64.6 % of patients ( n = 1,539 ) and 69.7 % of surgeons ( n = 318 ) . Logistic regression was used to examine the associations between surgeon specialization ( percentage of practice devoted to breast disease ) and hospital cancer program status , with four domains of patient satisfaction : ( 1 ) the surgical decision , ( 2 ) decision-making process , ( 3 ) surgeon-patient relationship , and ( 4 ) surgeon-patient communication , adjusting for patient and surgeon demographics and disease stage . RESULTS In this sample , 34.5 % of patients were treated by surgeons who devoted less than 30 % ( low volume ) of their practice to breast disease , 32.5 % by surgeons who devoted 30 % to 60 % ( medium volume ) of their practice to breast disease , and 33.0 % by surgeons who devoted more than 60 % ( high volume ) of their practice to breast disease . Compared to patients treated by low-volume surgeons , patients treated by higher volume surgeons were more satisfied with the decision-making process ( medium volume , odds ratio [ OR ] , 1.16 ; 95 % CI , 0.80 to 1.67 ; high volume : OR , 1.79 ; 95 % CI , 1.14 to 2.80 ) and with the surgeon-patient relationship ( medium volume : OR , 1.13 ; 95 % CI , 0.72 to 1.76 ; high volume : OR , 1.98 ; 95 % CI , 1.08 to 3.61 ) . Treatment setting was not associated with patient satisfaction after controlling for other factors . CONCLUSION Surgeon specialization is correlated with patient satisfaction . Examining the processes underlying these associations can inform strategies to improve breast cancer care BACKGROUND AND OBJECTIVE Most women with early stage breast cancer have the option of breast conserving therapy , which involves a partial mastectomy for removal of the primary tumor , usually followed by radiotherapy . The presence of tumor at or near the margin is strongly correlated with the risk of local tumor recurrence , so there is a need for a non-invasive , real-time tool to evaluate margin status . This study examined the use of autofluorescence and diffuse reflectance spectroscopy and spectral imaging to evaluate margin status intraoperatively . MATERIAL S AND METHODS Spectral measurements were taken from the surface of the tissue mass immediately following removal during partial mastectomies and /or from tissues immediately after sectioning by surgical pathology . A total of 145 normal spectra were obtained from 28 patients , and 34 tumor spectra were obtained from 12 patients . RESULTS After correlation with histopathology , a multivariate statistical algorithm classified the spectra as normal ( negative margins ) or tumor ( positive margins ) with 85 % sensitivity and 96 % specificity . A separate algorithm achieved 100 % classification between neo-adjuvant chemotherapy-treated tissues and non-treated tissues . Fluorescence and reflectance-based spectral images were able to demarcate a calcified lesion on the surface of a resected specimen as well . CONCLUSION Fluorescence and reflectance spectroscopy could be a valuable tool for examining the superficial margin status of excised breast tumor specimens , particularly in the form of spectral imaging to examine entire margins in a single acquisition CONTEXT Health care reform calls for increasing physician accountability and transparency of outcomes . Partial mastectomy is the most commonly performed procedure for invasive breast cancer and often requires reexcision . Variability in reexcision might be reflective of the quality of care . OBJECTIVE To assess hospital and surgeon-specific variation in reexcision rates following partial mastectomy . DESIGN , SETTING , AND PATIENTS An observational study of breast surgery performed between 2003 and 2008 intended to evaluate variability in breast cancer surgical care outcomes and evaluate potential quality measures of breast cancer surgery . Women with invasive breast cancer undergoing partial mastectomy from 4 institutions were studied ( 1 university hospital [ University of Vermont ] and 3 large health plans [ Kaiser Permanente Colorado , Group Health , and Marshfield Clinic ] ) . Data were obtained from electronic medical records and chart abstract ion of surgical , pathology , radiology , and outpatient records , including detailed surgical margin status . Logistic regression including surgeon-level r and om effects was used to identify predictors of reexcision . MAIN OUTCOME MEASURE Incidence of reexcision . RESULTS A total of 2206 women with 2220 invasive breast cancers underwent partial mastectomy and 509 patients ( 22.9 % ; 95 % CI , 21.2%-24.7 % ) underwent reexcision ( 454 patients [ 89.2 % ; 95 % CI , 86.5%-91.9 % ] had 1 reexcision , 48 [ 9.4 % ; 95 % CI , 6.9%-12.0 % ] had 2 reexcisions , and 7 [ 1.4 % ; 95 % CI , 0.4%-2.4 % ] had 3 reexcisions ) . Among all patients undergoing initial partial mastectomy , total mastectomy was performed in 190 patients ( 8.5 % ; 95 % CI , 7.2%-9.5 % ) . Reexcision rates for margin status following initial surgery were 85.9 % ( 95 % CI , 82.0%-89.8 % ) for initial positive margins , 47.9 % ( 95 % CI , 42.0%-53.9 % ) for less than 1.0 mm margins , 20.2 % ( 95 % CI , 15.3%-25.0 % ) for 1.0 to 1.9 mm margins , and 6.3 % ( 95 % CI , 3.2%-9.3 % ) for 2.0 to 2.9 mm margins . For patients with negative margins , reexcision rates varied widely among surgeons ( range , 0%-70 % ; P = .003 ) and institutions ( range , 1.7%-20.9 % ; P < .001 ) . Reexcision rates were not associated with surgeon procedure volume after adjusting for case mix ( P = .92 ) . CONCLUSION Substantial surgeon and institutional variation were observed in reexcision following partial mastectomy in women with invasive breast cancer BACKGROUND Breast-conserving surgery for palpable breast cancer is associated with tumour-involved margins in up to 41 % of cases and excessively large excision volumes . Ultrasound-guided surgery has the potential to resolve both of these problems , thereby improving surgical accuracy for palpable breast cancer . We aim ed to compare ultrasound-guided surgery with the st and ard for palpable breast cancer-palpation-guided surgery-with respect to margin status and extent of healthy breast tissue resection . METHODS In this r and omised controlled trial , patients with palpable T1-T2 invasive breast cancer were recruited from six medical centres in the Netherl and s between October , 2010 , and March , 2012 . Eligible participants were r and omly assigned to either ultrasound-guided surgery or palpation-guided surgery in a 1:1 ratio via a computer-generated r and om sequence and were stratified by study centre . Patients and investigators were aware of treatment assignments . Primary outcomes were surgical margin involvement , need for additional treatment , and excess healthy tissue resection ( defined with a calculated resection ratio derived from excision volume and tumour diameter ) . Data were analysed by intention to treat . This trial is registered at http://www.TrialRegister.nl , number NTR2579 . FINDINGS 134 patients were eligible for r and om allocation . Two ( 3 % ) of 65 patients allocated ultrasound-guided surgery had tumour-involved margins compared with 12 ( 17 % ) of 69 who were assigned palpation-guided surgery ( difference 14 % , 95 % CI 4 - 25 ; p=0·0093 ) . Seven ( 11 % ) patients who received ultrasound-guided surgery and 19 ( 28 % ) of those who received palpation-guided surgery required additional treatment ( 17 % , 3 - 30 ; p=0·015 ) . Ultrasound-guided surgery also result ed in smaller excision volumes ( 38 [ SD 26 ] vs 57 [ 41 ] cm(3 ) ; difference 19 cm(3 ) , 95 % CI 7 - 31 ; p=0·002 ) and a reduced calculated resection ratio ( 1·0 [ SD 0·5 ] vs 1·7 [ 1·2 ] ; difference 0·7 , 95 % CI 0·4 - 1·0 ; p=0·0001 ) compared with palpation-guided surgery . INTERPRETATION Compared with palpation-guided surgery , ultrasound-guided surgery can significantly lower the proportion of tumour-involved resection margins , thus reducing the need for re-excision , mastectomy , and radiotherapy boost . By achieving optimum resection volumes , ultrasound-guided surgery reduces unnecessary resection of healthy breast tissue and could contribute to improved cosmetic results and quality of life . FUNDING Dutch Pink Ribbon Foundation , Osinga-Kluis Foundation , Toshiba Medical Systems Mammographic screening increases the number of impalpable breast cancers requiring surgical excision . It is important to optimise the localisation technique to remove the smallest amount of tissue , still adequately excising the lesion . The last 65 wire-guided lumpectomies ( WGLs ) were compared vs. the first 65 radioguided occult lesion localisations ( ROLLs ) performed for impalpable breast cancers . Data collection included patient 's age , radiological abnormality , pre-operative core biopsy , type of primary surgery , length of localisation and excision , hospital stay , cancer size , weight and volume of the excised specimen , clearance margins . All patients were successfully localised with ROLL and WGL . Localisation time was reduced with ROLL ( P<0.001 ) . Clear margins were achieved in 83 % ROLLs and 57 % WGLs ( P=0.001 ) . Pathological cancer size and specimen weight were similar in both groups , although the specimen volume was slightly smaller for ROLL . A total of 74 % ROLLs had excellent cosmetic outcomes and 26 % good , vs. 55 % excellent and 45 % good in WGLs . A larger amount of normal breast tissue was excised with WGL , without achieving any better cancer clearance . ROLL provides a feasible alternative to WGL . This quick and simple technique achieves an improved rate of clear margins INTRODUCTION Twenty years ago prospect i ve r and omised controlled trials were initiated to compare conservative breast surgery plus radiation with radical mastectomy in the treatment of early-stage breast cancer . The results have shown no survival advantage for mastectomy over breast-conserving therapy ( BCT ) . However , local recurrence of cancer after BCT has been reported to be as high as 14 % , necessitating salvage mastectomy . METHODS This retrospective study was performed on 165 breast cancer patients undergoing BCT in the 12 years up to August 2002 . Resection and intraoperative cytological assessment were used to achieve clear excision margins . Adjuvant therapy ( hormones , chemotherapy ) was undertaken , and the incidence and times of local recurrence and distant metastases were recorded . RESULTS Ninety-four per cent of patients had clear margins at the initial operation . This was achieved irrespective of ductal carcinoma in situ alone or surrounding the cancer in 62 % of cases . At a median follow-up of 65 months one patient developed local recurrence ( LR ) in the breast synchronously with distant relapse . Two patients had non-nodal axillary recurrences but no patient suffered LR in isolation in the treated breast . CONCLUSION BCT is a safe alternative to mastectomy provided that the tumour is completely excised . The segment containing the cancer should be resected from the nipple to the periphery of the breast . Intraoperative cytological assessment helps to ensure clear margins . Reexcision is recommended for patients with close/involved margins Objective To evaluate the efficacy of intraoperative ultrasound in obtaining adequate surgical margins in women undergoing lumpectomy for palpable breast cancer . Summary Background Data Adequacy of surgical margins is a subject of debate in the literature for women undergoing breast-conserving therapy . The emerging technology of intraoperative ultrasound-guided surgery lends itself well to a prospect i ve study evaluating surgical accuracy and margin status after lumpectomy . Methods Two groups of women undergoing lumpectomy for palpable breast cancer were studied , one group using intraoperative ultrasound ( n = 27 ) and the other without ( n = 24 ) . Pathologic specimens were evaluated for size , margins , and accuracy , and patients were question ed about satisfaction with cosmetic results . Results Surgical accuracy was improved with intraoperative ultrasound-guided surgery . Margin status was improved , patient satisfaction was equivalent , and cost was not affected using ultrasound technology . Intraoperative ultrasound appears especially efficacious for women whose preoperative mammogram shows dense parenchyma surrounding the lesion . Conclusions The use of ultrasound-guided surgery optimizes the surgeon ’s ability to obtain satisfactory margins for breast-conserving techniques in patients with breast cancer . Patient satisfaction is excellent and a cost savings is most likely realized BACKGROUND The rate of involved margins after the excision of breast lesions using st and ard surgical techniques has historically ranged from approximately 20 % to 45 % . The localization and excision of breast lesions using intraoperative ultrasound has provided significant improvement . The authors report their collective experience with a novel technique utilizing the Phantom flexible loop electrosurgical device under ultrasound guidance for the intraoperative excision of breast lesions . METHODS Seventy-nine breast lesions were excised using the Phantom device with intraoperative ultrasound . Rate of reexcision , excised specimen size , and size of the lumpectomy incision were review ed . RESULTS Fifty-nine of 79 lesions were malignant . Fifty-one ( 86.4 % ) had noninvolved final margins ; 8 ( 13.6 % ) involved margins . The average specimen size was 21.3 cm3 , compared with a range of 60 to 100 cm3 in the literature . CONCLUSIONS These results demonstrate improved efficiency , a decrease in the volume of excision , smaller incision size , and very low need for reoperation secondary to involved margins using the Phantom device for real-time , ultrasound-guided lumpectomy Abstract Background : St and ard wire localization ( WL ) and excision of nonpalpable breast lesions has several shortcomings . Methods : Ninety-seven women with nonpalpable breast lesions were prospect ively r and omized to radioactive seed localization ( RSL ) or WL . For RSL , a titanium seed containing 125I was placed at the site of the lesion by using radiographical guidance . The surgeon used a h and held gamma detector to locate and excise the seed and lesion . Results : Both techniques result ed in 100 % retrieval of the lesions . Fewer RSL patients required resection of additional margins than WL patients ( 26 % vs. 57 % , respectively ; P = .02 ) . There were no significant differences in mean times for operative excision ( 5.4 vs. 6.1 minutes ) or radiographical localization ( 13.9 vs. 13.2 minutes ) . There were also no significant differences in the subjective ease of the procedures as rated by surgeons , radiologists , and patients . All WLs were carried out on the same day as the excision , whereas RSL was performed up to 5 days before the operative procedure . Conclusions : RSL is as effective as WL for the excision of nonpalpable breast lesions and reduces the incidence of pathologically involved margins of excision . RSL also reduces scheduling conflicts and may allow elimination of intraoperative specimen mammography . RSL is an attractive alternative to WL This study aims to vali date radioactive seed localization ( RSL ) as an alternative to wire localization ( WL ) in the operative excision of nonpalpable breast lesions . Eligible patients were recruited sequentially . A sample of 99 patients treated with WL was compared to the next 383 patients treated with RSL . Margins were considered " negative " if > or = 2 mm from in-situ and invasive disease . Pain and convenience scores were recorded on a 10-point scale . Patient characteristics and histology were similar . The lesion and localization device were retrieved in all patients . Margins of the first specimen were negative in 73 % of RSL patients , versus 54 % of WL patients ( p < 0.001 ) . A second operation was required in 8 % of RSL patients to achieve negative margins , versus 25 % of WL patients ( p < 0.001 ) . Pain scores were not statistically different . However , the RSL group had higher convenience scores ( p = 0.015 ) . RSL is safe , effective , and compared to WL , reduces the rates of intraoperative re-excision and reoperation for positive margins by 68 % . Patient satisfaction is improved with RSL . We strongly favor RSL over WL |
12,934 | 27,334,018 | Parent characteristics ( e.g. ethnicity , age , education , socioeconomic status ( SES ) ) were the most commonly reported predictors of participation for both recruitment and retention .
Being young , less educated , of an ethnic minority and having low SES appear to be barriers to participation in RCTs although there was little agreement between studies .
Conclusion Parent characteristics may predict participation of children and their families to RCTs ; however , there was a lack of consensus .
Whilst sociodemographic variables may be useful in identifying which groups are least likely to participate they do not provide insight into the processes and barriers to participation for children and families . | Background R and omised controlled trials ( RCTs ) are recommended as the ‘ gold st and ard ’ in evaluating health care interventions .
The conduct of RCTs is often impacted by difficulties surrounding recruitment and retention of participants in both adult and child population s. Factors influencing recruitment and retention of children to RCTs can be more complex than in adults .
There is little synthesis ed evidence of what influences participation in research involving parents and children .
Aim To identify predictors of recruitment and retention in RCTs involving children . | Background A commonly reported problem with the conduct of multicentre r and omised controlled trials ( RCTs ) is that recruitment is often slower or more difficult than expected , with many trials failing to reach their planned sample size within the timescale and funding originally envisaged . The aim of this study was to explore factors that may have been associated with good and poor recruitment in a cohort of multicentre trials funded by two public bodies : the UK Medical Research Council ( MRC ) and the Health Technology Assessment ( HTA ) Programme . Methods The cohort of trials was identified from the administrative data bases held by the two funding bodies . 114 trials that recruited participants between 1994 and 2002 met the inclusion criteria . The full scientific applications and subsequent trial reports su bmi tted by the trial teams to the funders provided the principal data sources . Associations between trial characteristics and recruitment success were tested using the Chi-squared test , or Fisher 's exact test where appropriate . Results Less than a third ( 31 % ) of the trials achieved their original recruitment target and half ( 53 % ) were awarded an extension . The proportion achieving targets did not appear to improve over time . The overall start to recruitment was delayed in 47 ( 41 % ) trials and early recruitment problems were identified in 77 ( 63 % ) trials . The inter-relationship between trial features and recruitment success was complex . A variety of strategies were employed to try to increase recruitment , but their success could not be assessed . Conclusion Recruitment problems are complex and challenging . Many of the trials in the cohort experienced recruitment difficulties . Trials often required extended recruitment periods ( sometimes supported by additional funds ) . While this is of continuing concern , success in addressing the trial question may be more important than recruitment alone This paper reports findings on parental engagement in a community-based parent training intervention . As part of a r and omized trial , 821 parents were offered group-based Triple P as a parenting skills prevention program . Program implementation was conducted by practitioners . The intervention was implemented between Waves 1 and 2 of a longitudinal study , with a participation rate of 69 % and a retention rate of 96 % . The study finds that a practitioner-led dissemination can achieve recruitment and completion rates that are similar to those reported in research er-led trials . Second , the study found that different factors are associated with the various stages of the parental engagement process . Family-related organizational and timing obstacles to participation primarily influence the initial stages of parental involvement . The strength of neighborhood networks plays a considerable role at the participation and completion stages of parental engagement . The general course climate and the intensity of program exposure predict the utilization of the program several months after the delivery Background As the number of r and omised controlled trials of medicines for children increases , it becomes progressively more important to underst and the experiences of parents who are asked to enrol their child in a trial . This paper presents a narrative review of research evidence on parents ' experiences of trial recruitment focussing on qualitative research , which allows them to articulate their views in their own words . Discussion Parents want to do their best for their children , and socially and legally their role is to care for and protect them yet the complexities of the medical and research context can challenge their fulfilment of this role . Parents are simultaneously responsible for their child and cherish this role yet they are dependent on others when their child becomes sick . They are keen to exercise responsibility for deciding to enter a child in a trial yet can be fearful of making the ' wrong ' decision . They make judgements about the threat of the child 's condition as well as the risks of the trial yet their interpretations often differ from those of medical and research experts . Individual parents will experience these and other complexities to a greater or lesser degree depending on their personal experiences and values , the medical situation of their child and the nature of the trial . Interactions at the time of trial recruitment offer scope for negotiating these complexities if practitioners have the flexibility to tailor discussion s to the needs and situation of individual parents . In this way , parents may be helped to retain a sense that they have acted as good parents to their child whatever decision they make . Summary Discussing r and omised controlled trials and gaining and providing informed consent is challenging . The unique position of parents in giving proxy consent for their child adds to this challenge . Recognition of the complexities parents face in making decisions about trials suggests lines for future research on the conduct of trials , and ultimately , may help improve the experience of trial recruitment for all parties PURPOSE Loss of participants in r and omized clinical trials threatens the validity of study findings . The purpose of this study was to determine pre-r and omization predictors of study completion status throughout the course of a r and omized clinical trial involving young children with type 1 diabetes and their primary caregivers . METHODS An intervention to improve adherence to the diabetes treatment regimen was delivered as part of the child 's regular 3-month diabetes clinic visit . The study protocol involved 7 clinic visits across 18 months for the Immediate Treatment group and 9 clinic visits across 24 months for the Delayed Treatment group . Among those who completed the study and regardless of treatment group , participants were categorized into two groups : On-Time Completers ( n=41 ) and Late Completers ( n=39 ) . Demographic , disease , and psychosocial characteristics of children and their primary caregivers measured prior to study r and omization were tested for their association with the participants ' completion status ( i.e. , On-Time Completers , Late Completers , or Withdrawals ) . RESULTS Of the 108 participants , 28 ( 25.9 % ) withdrew and 80 ( 74.1 % ) completed the study . On-Time Completers ( i.e. , study completed within 4 months of expected date ) were more likely to have private insurance and primary caregivers with some college education . Late Completers ( i.e. , study completion took longer than 4 months ) were more likely to be boys and to have primary caregivers who reported mild to moderate levels of depression . Children who subsequently withdrew from the study reported poorer diabetes-related quality of life and poorer school-related quality of life at study inception and were more likely to have primary caregivers who did not work outside the home . CONCLUSIONS Pre-r and omization screening of participants on both demographic and psychological variables may help identify those at greatest risk for study withdrawal or poor study protocol adherence , permitting the investigators to develop retention strategies aim ed at this high-risk group Background Despite important implication s for the budgets , statistical power and generalisability of research findings , detailed reports of recruitment and retention in r and omised controlled trials ( RCTs ) are rare . The NOURISH RCT evaluated a community-based intervention for first-time mothers that promoted protective infant feeding practice s as a primary prevention strategy for childhood obesity . The aim of this paper is to provide a detailed description and evaluation of the recruitment and retention strategies used . Methods A two stage recruitment process design ed to provide a consecutive sampling framework was used . First- time mothers delivering healthy term infants were initially approached in postnatal wards of the major maternity services in two Australian cities for consent to later contact ( Stage 1 ) . When infants were approximately four months old mothers were re-contacted by mail for enrolment ( Stage 2 ) , baseline measurements ( Time 1 ) and subsequent r and om allocation to the intervention or control condition . Outcomes were assessed at infant ages 14 months ( Time 2 ) and 24 months ( Time 3 ) . Results At Stage 1 , 86 % of eligible mothers were approached and of these women , 76 % consented to later contact . At Stage 2 , 3 % had become ineligible and 76 % could be recontacted . Of the latter , 44 % consented to full enrolment and were allocated . This represented 21 % of mothers screened as eligible at Stage 1 . Retention at Time 3 was 78 % . Mothers who did not consent or discontinued the study were younger and less likely to have a university education . Conclusions The consent and retention rates of our sample of first time mothers are comparable with or better than other similar studies . The recruitment strategy used allowed for detailed information from non-consenters to be collected ; thus selection bias could be estimated . Recommendations for future studies include being able to contact participants via mobile phone ( particularly text messaging ) , offering home visits to reduce participant burden and considering the use of financial incentives to support participant retention . Trial registration Australian and New Zeal and Clinical Trials Registry Number The hierarchy of evidence in assessing the effectiveness of interventions or treatments is explained , and the gold st and ard for evaluating the effectiveness of interventions , the r and omised controlled trial , is discussed . Issues that need to be considered during the critical appraisal of r and omised controlled trials , such as assessing the validity of trial methodology and the magnitude and precision of the treatment effect , and deciding on the applicability of research results , are discussed . Important terminologies such as r and omisation , allocation concealment , blinding , intention to treat , p values , and confidence intervals are explained OBJECTIVES To operationalize a comprehensive description of attrition , including pre- inclusion , dropout , and attrition due to intermittent missing data , and to test a predictive model of attrition using a data set from a r and omized controlled intervention in pediatric asthma . METHODS Participants included children , ages 4 - 12 , diagnosed with asthma and their caregivers . Demographic variables and outcome measures of asthma morbidity were examined in 327 families to determine their association with attrition . RESULTS Families who did not complete r and omization and the intervention tended to have younger caregivers than did completers . Caregiver age emerged as the most consistent predictor of pre- inclusion and dropout attrition . There were no significant predictors of attrition due to intermittent missing data . CONCLUSION Younger caregivers may be at particular risk for attrition in pediatric asthma intervention studies and warrant special attention by investigators OBJECTIVE To examine attrition variables in r and omized controlled trials of cognitive behavioral interventions for children with chronic illnesses . METHODS We examined attrition rates reported on 40 r and omized cognitive behavioral interventions published in six pediatric research journals , during the years 2002 - 2007 . Intervention focus was limited to children with a chronic medical condition , such as asthma , obesity , arthritis , diabetes , cancer , sickle cell disease , and cystic fibrosis . RESULTS Mean rate of enrollment refusal was 37 % ( range 0 - 75 % ) . Mean attrition rate was 20 % ( range 0 - 54 % ) for initial follow-up and 32 % ( range 0 - 59 % ) for extended follow-up . Of the review ed articles , 40 % included a CONSORT diagram . CONCLUSIONS Strategies that can be used to limit attrition include tailoring recruitment to the study population , providing personalized feedback , maintaining consistent study procedures , providing incentives , and using intensive tracking measures . There is a need for st and ardized definitions and reporting of attrition rates in r and omized cognitive behavioral intervention studies OBJECTIVES Survival rates for childhood cancer have improved substantially partly as a result of national and international r and omized clinical trials ( RCT ) . However , the decision for families is complex and emotional . Our aim was to describe the views of mothers of children newly diagnosed with ALL regarding consent to r and omized controlled trials . DESIGN Qualitative interview to explore mothers knowledge , and reasons for involving their child in RCTs . Interviews took place in mothers ' homes . PARTICIPANTS Fifty mothers of children with newly diagnosed ALL ( age 4 - 16 years ; mean = 7.4 ) recruited through research nurses at outpatient appointments . RESULTS All but three families had consented for their child to be treated in the RCT , although there was wide variation in their underst and ing of the aims , costs and benefits . Most mothers reported the aim of the trial to compare ' old ' and ' new ' treatments . CONCLUSION Despite detailed verbal and written information , mothers were poorly informed about the purpose of the trial , and possibility of side effects . Individual preferences for either st and ard or new treatment were routinely reported . The data raise questions about the extent to which families give truly informed consent to recruitment of their child to an RCT A significant percentage of children with disruptive behavior disorders do not receive mental health assistance . Utilization is lowest among groups whose children are at greatest risk . To increase the availability , accessibility , and cost efficacy of parent training programs , this prospect i ve r and omized trial compared a large group community-based parent training program to a clinic-based individual parent training ( PT ) programs . All families of junior kindergartners in the Hamilton public and separate school boards were sent a checklist regarding problems at home . Those returning question naires above the 90th percentile were block r and omly assigned to : ( 1 ) a 12-week clinic-based individual parent training ( Clinic/Individual ) , ( 2 ) a 12-week community-based large group parent training ( Community/Group ) , or ( 3 ) a waiting list control condition . Immigrant families , those using English as a second language , and parents of children with severe behaviour problems were significantly more likely to enroll in Community/Groups than Clinic/Individual PT . Parents in Community/Groups reported greater improvements in behaviour problems at home and better maintenance of these gains at 6-month follow-up . A cost analysis showed that , with groups of 18 families , Community/Groups are more than six times as cost effective as Clinic/Individual programs Women with inadequate prenatal care were recruited to a multi-component parenting intervention study . Because it was anticipated that this high-risk population might present challenges to retention , a variety of strategies were employed to maintain their participation in the study . This report review s the results of these retention efforts and compares the population that completed the study versus those that terminated prior to study completion . Two hundred and eighty-six women were r and omized to an intervention or control group . Careful tracking of the mothers , offering incentives for completing various study activities and providing a culturally competent staff were among the strategies employed to maintain participation . Comparison was made of those mothers terminating before study completion versus those retained , and of those terminating early in the study period versus later . Despite retention efforts , attrition at a level of 41 % occurred . A few characteristics of mothers terminating early from the study were significant including older maternal age , a larger number of children , and incidence of no prenatal care . Despite comprehensive tracking procedures , some mothers were lost to follow up after change of residence . Other reasons for attrition included child outplacement and refusal of services or data collection procedures OBJECTIVE To explore parents ' attitudes to children 's participation in r and omized controlled trials . STUDY DESIGN Qualitative analysis of focus group discussion s involving 33 parents from a pediatric teaching hospital and local school in Australia . Parents varied in age , gender , ethnicity , level of education , research experience , and child 's health status . The transcribed discussion s were analyzed by theme linkage using the constant comparative method . RESULTS Parents balance risks and benefits when deciding about trial participation for their child . Perceived benefits include the offer of hope , better care of their child , the opportunity to access new treatments , healthcare professionals and health information , meeting others in similar circumstances , and helping others . Perceived risks include potential side effects , being r and omized to ineffective treatments , and the inconvenience of participation . The decision for trial participation is also influenced by parental factors ( parents ' knowledge , beliefs , and emotional responses ) , child factors ( the child 's health status and preference about participation ) , trial factors ( the use of placebos and uncertainties of participation ) , and doctor factors ( doctor 's recommendations and communication of trial information ) . CONCLUSIONS Educating parents about trials , improving communication between trialists , pediatricians , and parents , increasing incentives while decreasing inconveniences , and providing decision aids for parents may increase parents ' willingness to participate in trials Predictors of attrition from individual parent – child interaction therapy were examined for 99 families of preschoolers with disruptive behavior disorders . Seventy-one percent of treatment dropouts were identified by lower SES , more maternal negative talk , and less maternal total praise at pretreatment . Following PCIT , families were r and omly assigned to an Assessment -Only or Maintenance Treatment condition . Higher maternal distress predicted 63 % of dropouts in the Assessment -Only condition . Lower maternal intellectual functioning predicted 83 % of dropouts from Maintenance Treatment . Findings highlight a continuing need for evidence -based retention strategies at various phases of engagement in PCIT OBJECTIVE The process of recruitment into r and omized controlled trials is not often reported . In the present paper , the methods used for recruitment into the Childhood Asthma Prevention Study are reported and the reasons why eligible subjects chose not to participate or withdrew from the trial are examined . METHODOLOGY Recruitment was conducted at the antenatal clinics of six hospitals in Sydney ( NSW , Australia ) . Pregnant women with a family history of asthma who consented to participate were r and omized into one of four groups and were asked to follow a set of interventions . The study will continue until the infants are 5 years old . RESULTS Of 7171 women screened , 2095 ( 29.2 % ) were eligible , of whom only 616 ( 29.4 % of eligible women ) were recruited . The main reasons for not taking part in the study were a lack of interest , in eligibility ( on further question ing ) , inability to be contacted and ' too busy ' . During the first 21/2 years of the trial , 10 % of participants withdrew . The most common reasons for withdrawal from the study were loss of contact , family moving interstate or overseas and medical reasons . In families that withdrew from the trial or who were eligible but did not participate , the parents were significantly younger , mothers were less educated and fathers were less likely to be in full-time employment . CONCLUSIONS By collecting demographic data on people who withdrew from the study and chose not to participate , we gained a better underst and ing of why our recruitment rate was low . The preferential recruitment of some sectors of the community has important implication s for the ways in which future studies will be planned Despite the potential of parent training as a prevention and behavioral family intervention strategy , there are a number of important issues related to implementation ( e.g. , recruitment and retention of families ) . This paper presents recruitment and retention data from families enrolling in a r and omized controlled universal prevention trial for child behavior problems conducted in Germany . The recruitment rate averaged 31 % ( general project participation ) , with families of lower socioeconomic status ( SES ) participating at a lower rate . Project-declining families most often reported intrusion of privacy as their primary concern . In contrast , once parents were enrolled in the project , participation among those r and omized to the parent training group averaged 77 % ( program/intervention participation ) ; non-participation was mostly due to logistical issues . Parents accepting the offer of parent training were more likely to report child behavior problems than did declining parents . Although parents from more disadvantaged areas had a lower overall level of participation in the project once recruited , parents with children having higher levels of behavior problems indeed were more likely to participate in the intervention . Different recruitment methods may be required to engage high-risk families from socioeconomically disadvantaged areas to further improve community-level impact on child mental health We report on recruiting and retaining a sample of low birth weight , premature infants for a clinical trial as well as results of tests evaluating sampling and retention biases . A total of 4551 infants were screened , and 1302 were found eligible . Consent was obtained for 1028 infants . After r and omization and the presentation of group assignment , the number of infants enrolled was 985 ( 75.7 % of those eligible ) . Of these , 92.7 % completed the 3-year study . Tests to evaluate recruitment bias revealed significant relationships between nonenrollment and site , maternal race , and infant birth weight . Tests to evaluate retention bias revealed a significant relationship between dropout and maternal education . Additionally , infant birth weight and maternal age interacted with treatment in predicting dropout . Despite these statistically significant recruitment and retention biases , there was no evidence of problems with sample representativeness to the population of interest or of treatment group differences on study -relevant background variables . J Dev Behav Pediatr 14:1–7 , 1993 . Index terms : bias , infant , recruitment , retention , sample Objective —To compare demographic and disease-specific characteristics of children included in a trial of the effectiveness of adenotonsillectomy with those of children who , although eligible , were not r and omized . Material and Methods —Characteristics were compared between ( i ) r and omized children ( n=270 ) ; ( ii ) eligible children whose parents immediately decided not to participate ( n=243 ) ; and ( iii ) eligible children whose parents were informed about the trial by a member of the study team but did not give their informed consent for participation in the trial ( n=406 ) . Results —Statistically significant but relatively small differences were observed between the groups . Notably , breathing difficulties at night and abnormal appearance of the tonsils were more prevalent among eligible children whose parents immediately refused participation in the trial than in the other two groups . In contrast , cervical lymphadenopathy and previous ENT surgery were less prevalent among eligible children whose parents immediately refused participation in the trial . Conclusion —Few and relatively small differences were observed between r and omized and eligible , non-r and omized children . The trial population appears to be representative of the relevant patient domain , i.e. children currently undergoing adenotonsillectomy in The Netherl and This study examined factors associated with the utilization of universally available school-based parent training . In a r and omly selected , prospect ively screened , unreferred community sample of 1,498 5- to 8-year-olds , 28 % to 46 % of families of children with high parent-reported externalizing problems enrolled . Externalizing problems , first-child status , and a high school education were associated with increased enrollment . Single-parent status , immigrant background , and limited extracurricular child activities were associated with lower enrollment . Economic disadvantage , stress , family dysfunction , and parental depressive symptoms were not associated with participation . Most families attributed nonparticipation to busy personal schedules , inconvenient times , and logistical difficulties BACKGROUND Subject dropout from a prospect i ve , longitudinal trial can produce biases in the remaining sample that affect study findings and their interpretation , yet little is known about factors contributing to dropout . OBJECTIVE To determine characteristics differentiating those who complete from those who drop out of a longitudinal multicenter clinical trial . METHODS In this study , 578 parents and other caretakers of infants at risk for cardiopulmonary arrest enrolled in a longitudinal trial investigating the psychosocial impact of cardiopulmonary resuscitation training . In this secondary analysis , the baseline sociodemographic , emotional , psychosocial , and infant characteristics of those who dropped from the trial were compared with those who completed the study . RESULTS The study was completed by 60 % ( n = 347 ) of the participants . Those most likely to drop out were fathers or other caretakers ( vs. mothers ) employed outside the home who spoke English ( vs. Spanish ) ; were assigned to an experimental group ( vs. a control group ) ; had higher levels of depression , hostility , and overall psychosocial distress ; and held negative views about health care . CONCLUSION Although a few sociodemographic characteristics differentiated dropouts from completers , personal , emotional and psychosocial factors were the predominant predictors of dropouts . Other reputed sources of retention difficulties ( e.g. , income , education , minority status , lack of social support , or problems with family functioning ) did not predict dropout BACKGROUND Recruitment and participation in clinical trials by minorities , particularly African Americans and rural underserved population s , are low . This report examines predictors of clinical trial recruitment and participation for adult Maryl and ers . METHODS A cross-sectional design was used to survey 5154 adults ( 18 years and older ) residing in 13 of the 24 jurisdictions in Maryl and , including urban Baltimore City , and the rural regions of Western Maryl and and the Eastern Shore . The survey , conducted between December 2001 and March 2003 , used Computer-Assisted Telephone Interviewing and r and om-digit dialing procedures . Primary dependent variables included " ever asked to participate " ( i.e. , recruited ) and " participated " in clinical trials . RESULTS 11.1 % of the respondents had been recruited to clinical trials . In addition , 59.4 % of the respondents recruited to clinical trials actually participated in a clinical trial . Among respondents recruited to clinical trials , black and middle income respondents were significantly less likely to actually participate in clinical trials ; whereas , respondents who received information about clinical trials from their health care provider , who were knowledgeable about clinical trials , and those who had the time commitment were significantly more likely to participate in clinical trials . CONCLUSIONS These results suggest serious gaps in efforts to recruit racial/ethnic minorities and residents of rural regions into clinical trials . The findings provide the basis for the development and implementation of community-based educational programs for both the general public and health care professionals , and to enhance availability of community-based clinical trials , especially in the rural areas of the state Recruitment and retention of subjects is critically important for the conduct of r and omized clinical trials . When significant effort is given toward recruiting members of ethnic minorities in a sample , a similar rate of retention for all subgroups of subjects is essential . Little is known about why research subjects withdraw consent to participate in research and whether attrition is influenced by ethnicity or other factors . The purpose of this study was to determine the reasons for withdrawal from a large , multicenter r and omized trial and whether these reasons differed among ethnic and gender subgroups . Additionally , we were interested in comparing withdrawn subjects to matched subjects who stayed in the trial to determine what factors encouraged full study completion . Using a cohort survey design , adult subjects ( n = 35 ) who withdrew from a large , multicenter r and omized trial and matched subjects who completed the study ( n = 35 ) were interviewed by telephone after study completion . Subjects who withdrew consent tended to be female and members of ethnic minorities . The most frequent problems-reported significantly more often by subjects who withdrew consent compared to matched retained subjects-were interference with work , lack of time , complicated and cumbersome record-keeping requirements , difficult study medicine regimens , and difficulty rescheduling appointments due to lack of flexibility on the part of study personnel . Only 17 % of withdrawn subjects were satisfied with the overall research experience compared to 52 % of matched retained subjects . Matched subjects who completed all required visits in the r and omized controlled trial reported three reasons that promoted completion : remuneration , commitment to finish , and belief that the study was important Subject loss in a cohort of 645 infants and their families , enrolled in a multicenter clinical trial , was described . Medical/biologic , socioeconomic and social support ( Environmental Quality Index [ EQI ] composite ) , and developmental outcome data were obtained . Dropout was evaluated by comparing infants who withdrew at any time throughout the study to those who remained , as well as at four different time periods between 40 weeks conceptional age and 36 months . A dropout profile was also developed . Overall dropout was predicted by EQI score , clinical center , gestational age category , and 18-month developmental status . In addition to these variables , the dropout profile included race , but not 18-month developmental status . Medical/biologic variables , environmental quality , and race and center were most influential in the first , second and third , and fourth time periods , respectively . The identification of factors which are associated with increased subject loss can help research ers project needed sample sizes in future studies Studies reporting clinical and non- clinical parameters of participants and non- participants of clinical trials are scarce . In the available studies non- participants were likely to show less favourable outcomes than participants on both socioeconomic parameters as well as on caries experience . However , the impact of non-participation on the total sample of the research population is not established . In the present study , as part of baseline data collection for a r and omized controlled trial on caries-preventive strategies , 346 parents of children 6.0 years ( ± 3 months ) of age were approached to let their child participate . Sixty parents refused , but 56 of them were willing to fill out the same set of question naires and to allow their child to be clinical ly examined once . Parents from participating children had higher socioeconomic status , were more often of autochthonous origin and scored better on knowledge questions than parents of non-participating children . Furthermore , parents of participating children reported a higher willingness to invest , were more likely to hold on to regular meals and their child had lower levels of plaque compared to non-participating children . Surprisingly , the participating children had higher dmfs scores than the non-participating children . Their care index ( fs/ds + fs ) was higher than that of non-participating children . Based on the findings of this study , the presumption that non-participating children will show less favourable clinical outcomes can not be supported . Although participants differed from non- participants , they did not differ from the total population . It is suggested that the external validity of a r and omized controlled trial on caries-preventive strategies is not necessarily affected by non-participation bias TARGET ( Trial of Alternative Regimens in Glue Ear Treatment ) is a multicentre UK r and omized controlled trial ( RCT ) comparing bilateral ventilation tubes with and without adjuvant adenoidectomy against non-surgical management in children with bilateral , persistent otitis media with effusion ( OME ) . This paper compares the recruited and r and omized children with those that , although eligible , were not included in the RCT for various reasons . This is necessary to identify any potential bias in the overall estimate of treatment effectiveness . At the first visit , 1315 children with OME satisfied the criteria of age ( 3 years 3 months-6 years 9 months ) , no previous ear or adenoid surgery , tympanometric evidence of fluid ( bilateral B or B + C2 ) and a hearing loss ( conductive loss in both ears of > or = 20 dBHL ) . Of these children , 151 ( 11 % ) were not followed up because of overriding concern and 70 ( 5 % ) because of parental refusal . Of the 506 children eligible for r and omization , because of persistence over 12 weeks of watchful waiting of bilateral OME with the same criteria , 20 ( 4 % ) were not r and omized because of overriding concern and 75 ( 15 % ) because of parental refusal . The distribution of the potential effect modifiers was determined for each group . At the first visit , the only significant differences ( P < 0.05 ) , comparing those not recruited because of overriding concern with those recruited , were in respect of sex ( 61 % girls compared with 52 % boys ) and hearing level ( 34.6 compared with 33.0 dBHL ) . At the second visit , the only significant difference involved less frequent upper respiratory tract infections ( URTIs ) in children whose parents refused to allow r and omization ( 8 % compared with 18 % had had episodic URTI more often than once every 3 months ) . It is probable that the findings from the TARGET trial will translate to the entire clinic population in this age group as long as they meet the same audiometric and tympanometric criteria . The differences found can be h and led by presentation of disaggregated results This is a protocol for a Cochrane Review ( Methodology ) . The objectives are as follows : To quantify the effect of strategies to reduce attrition in r and omised trials . To investigate if there is a variation in effect by type of strategy , trial setting and disease area Background Recruitment and retention in clinical trials of minorities is low , particularly in rural underserved population s. This has slowed progress in addressing racial/ethnic disparities in oral health . Purpose To describe factors associated with successful recruitment , and identify predictors of continued retention of pregnant women attending a community health center into a r and omized controlled clinical trial to prevent early childhood caries . Methods The Mothers and Youth Access ( MAYA ) Trial recruited women in the second trimester of pregnancy . At baseline , consenting women completed an oral health question naire and received a dental exam and oral health counseling . Four months postpartum , women returned with their babies for r and omization with follow up at 9- , 12- , 18- , 24- , 30- , and 36-month postpartum visits . To assess predictors of retention , data about respondents ' demographics , and oral health-related knowledge , attitudes , and behaviors were obtained by question naire and analyzed by logistic and discrete time-to-event regression analyses . Results Of 556 predominantly Mexican-American women recruited at baseline , 195 ( 35 % ) were excluded after baseline for not meeting inclusion criteria ; 361 ( 65 % ) continued to r and omization . Factors such as race/ethnicity , annual household income , household composition , oral health-related knowledge and behaviors significantly related to retention until r and omization . In multivariable models , women reporting a higher annual household income were less likely to be lost to attrition before r and omization ( odds ratio = 0.73 , 95 % confidence interval ( CI ) 0.60—0.89 ) ; while Mexican/Mexican-American women were less likely to be lost beyond r and omization ( hazard ratio = 0.53 , 95 % CI 0.26—1.08 ) . Limitations Factors not measured at baseline may have been important in predicting attrition . The MAYA Trial is expected to finish by November 2008 ; therefore , complete results for total retention may differ from those reported here . Conclusions Recruitment and retention efforts for pregnant Hispanic women should place heavy emphasis on culture as ethnicity remained the only borderline significant predictor in postr and omization retention . Clinical Trials 2008 ; 5 : 336—346 . |
12,935 | 22,672,854 | Antispasmodics were more effective than placebo in IBS , without any significant adverse events .
The addition of simethicone improved the properties of the antispasmodic agents , as seen with the alverine/simethicone and pinaverium/simethicone combinations | INTRODUCTION Irritable bowel syndrome ( IBS ) is characterized by recurrent abdominal pain , bloating , and changes in bowel habit .
AIMS To determine the clinical effectiveness of the antispasmodic agents available in Mexico for the treatment of IBS . | Seventy-two patients complaining of abdominal pain were studied in a double blind trial with otilonium bromide ( OB ) ( 40 mg tid or placebo ) . In our patients we performed , before and after the treatment , a clinical evaluation ( symptom variations ) and functional studies ( sigmoid manometry during bowel distension ) . As regards clinical parameters , otilonium bromide significantly reduced abdominal pain and bloating and significantly increased ( p less than 0.02 ) the pain threshold . However the comparison with the placebo group did not show any difference between the two groups . Sigmoid motility during distension was significantly reduced ( p less than 0.05 ) in OB group , whereas it did not change in the placebo group . We can conclude that , in irritable bowel syndrome ( IBS ) patients , OB is able to improve symptoms and to reduce stimulated motor activity of the sigmoid A double-blind controlled therapeutic trial of factorial design was used to study the therapeutic effects of lorazepam , hyoscine butylbromide , and ispaghula husk in 12 r and omised blocks of eight patients with the irritable bowel syndrome ( IBS ) . Each of the three agents caused a sustained symptomatic improvement in some of the patients , although only with ispaghula was the difference between the real and dummy preparation statistically significant . When the eight possible combinations of treatment were analysed none of the 12 patients who received only dummy preparations of the three agents had maintained any improvement over the three months of the trial . Seven patients improved among the 12 who received potent preparations of all three agents , and between four and six patients improved in the groups receiving one or two of the potent preparations . These therapeutic results , though far from perfect , show that the types of drug commonly used to treat IBS are of some value and may be additive in their effects . Similar combinations of other therapeutic agents may be more effective , but it will be possible to determine this only by carrying out factorial therapeutic trials As professionals , we want to use the best treatments ; as patients , we want to be given them . Knowing whether an intervention works ( or does not work ) is fundamental to clinical decision making . However , clinical decision making involves more than simply taking published results of research directly to the bedside . Physicians need to consider how similar their patients are to those in the published studies , to take the values and preferences of their patients into account , and to consider their own experience with a given test or treatment . Evidence from clinical research is becoming increasingly important in medical- practice decisions as more and better evidence is published . But when is the evidence strong enough to justify changing a practice ? Individual studies that involve only small numbers of patients may have results that are distorted by the r and om play of chance and thus lead to less than optimal decisions . As is clear from other papers in this series , systematic review s identify , critically appraise , and review all the relevant studies on a clinical question and are more likely to give a valid answer . They use explicit methods and quality st and ards to reduce bias . Their results are the closest we can come to reaching the truth given our current state of knowledge . The questions about an intervention that a systematic review should answer are the following : 1 . Does it work ? 2 . If it works , how well does it work in general and compared with placebo , no treatment , or other interventions that are currently in use ? 3 . Is it safe ? 4 . Will it be safe and effective for my patients ? Whereas the critical appraisal and qualitative synthesis provided by review articles can be interpreted directly , the numerical products of quantitative review s can be more difficult to underst and and apply in daily clinical practice . This paper provides guidance on how to interpret the numerical and statistical results of systematic review s , translate these results into more underst and able terms , and apply them directly to individual patients . Many of these principles can also be used to interpret the numerical results of individual clinical studies . They are particularly relevant to systematic review s , however , because such review s contain more information than do primary studies and often exert greater influence than do individual studies . Making Sense of the Numerical Results of Clinical Studies Although the results of clinical studies can be expressed in intuitively meaningful ways , such results do not always easily translate into clinical decision making . For example , results are frequently expressed in terms of risk , which is an expression of the frequency of a given outcome . ( Risks are probabilities , which can vary between 0.0 and 1.0 . A probability of 0.0 means that the event will never happen , and a probability of 1.0 means that it always happens . ) Consider a hypothetical study of the recurrence of migraine headaches in a control group receiving placebo and a treatment group receiving a new antimigraine preparation , drug M ( a secondary prevention trial ) . Suppose that at the end of the trial , migraines recurred in 30 % of the control group ( the risk for recurrence was 0.30 ) but in only 5 % of the drug M group ( risk of 0.05 ) ( Table 1 ) . Table 1 . Numerical Expression of Hypothetical Clinical Trial Results The outcomes of the study are clear enough for the two groups when they are examined separately . But clinicians and patients are more interested in the comparative results , that is , the outcome in one group relative to the outcome in the other group . This overall ( comparative ) result can be expressed in various ways . For example , the relative risk , which is the risk in the treatment group relative to that in the control group , is simply the ratio of the risks in the two groups . In other words , relative risk is the risk in the treatment group divided by that in the control group , 0.05 0.30 , or 0.17 . The comparison can also be expressed as the reduction in relative risk , which is the ratio between the decrease in risk ( in the treatment group ) and the risk in the control group , 0.25 0.30 , or 0.83 ( Table 1 ) . ( The relative risk reduction can also be calculated as 1 relative risk ) . Although the clinical meaning of relative risk ( and relative risk reduction ) is reasonably clear , relative risk has the distinct disadvantage that a given value ( for example , 0.17 ) is the same whether the risk with treatment decreases from 0.80 to 0.14 , from 0.30 to 0.05 , from 0.001 to 0.00017 , and so forth . The clinical implication s of these changes clearly differ from one another enormously and depend on the specific disease and intervention . An important alternate expression of comparative results , therefore , is the absolute risk reduction . Absolute risk reduction is determined by subtracting the risk in one group from the risk in the other ( for example , the risk in the treatment group is subtracted from the risk in the placebo group ) . In the case of our migraine study , the absolute risk reduction would be 0.30 0.05 , which equals 0.25 , or 25 percentage points . In contrast , for a study in which the risk decreased from 0.001 to 0.00017 , the absolute risk reduction would be only 0.00083 , or 0.083 percentage points , which is a trivial change in comparison ( Table 1 ) . This arithmetic emphasizes the difficulty of expressing the results of clinical studies in meaningful ways . Relative risk and relative risk reduction clearly give a quantitative sense of the effects of an intervention in proportional terms but provide no clue about the size of an effect on an absolute scale . In contrast , although it tells less about proportional effects , absolute risk says a great deal about whether an effect is likely to be clinical ly meaningful . Despite this benefit , even absolute risk is problematic because it is a dimensionless , abstract number ; that is , it lacks a direct connection with the clinical situation in which the patient and physician exist . However , another way of expressing clinical research results can provide that clinical link : the number needed to treat ( NNT ) . Number Needed To Treat The NNT for a given therapy is simply the reciprocal of the absolute risk reduction for that treatment [ 1 , 2 ] . In the case of our hypothetical migraine study ( in which risk decreased from 0.30 without treatment with drug M to 0.05 with treatment with drug M , for a relative risk of 0.17 , a relative risk reduction of 0.83 , and an absolute risk reduction of 0.25 ) , the NNT would be 1 0.25 , or 4 . In concrete clinical terms , an NNT of 4 means that you would need to treat four patients with drug M to prevent migraine from recurring in one patient . To emphasize the difference between the concepts embodied in NNT and relative risk , recall the various situations mentioned above , in all of which the relative risk was 0.17 but in which the absolute risk decreased from 0.80 to 0.14 in one case and from 0.001 to 0.00017 in another . Note that the corresponding NNTs in these two other cases are 1.5 and 1204 , respectively : that is , you would need to treat 1.5 and 1204 patients to obtain a therapeutic result in these two situations compared with 4 patients with drug M ( Table 1 ) . The NNT can be calculated easily and kept as a single numerical reminder of the effectiveness ( or , as we will see , the potential for harm ) of a particular therapy . As we suggested , the NNT has the crucial advantage of direct applicability to clinical practice because it shows the effort that is required to achieve a particular therapeutic target . The NNT has the additional advantage that it can be applied to any beneficial outcome or any adverse event ( when it becomes the number needed to harm [ NNH ] ) . The concept of NNT always refers to a comparison group ( in which patients receive placebo , no treatment , or some other treatment ) , a particular treatment outcome , and a defined period of treatment . In other words , the NNT is the number of patients that you will need to treat with drug or treatment A to achieve an improvement in outcome compared with drug or treatment B for a treatment period of C weeks ( or other unit of time ) . To be fully specified , NNT and NNH must always specify the comparator , the therapeutic outcome , and the duration of treatment that is necessary to achieve the outcome . Important Qualities of the Number Needed To Treat The NNT is treatment specific . It describes the difference between treatment and control in achieving a particular clinical outcome . Table 2 shows NNTs from a selection of systematic review s and large r and omized , controlled trials . Table 2 . Numbers Needed To Treat from Systematic Review s and R and omized , Controlled Trials A very small NNT ( that is , one that approaches 1 ) means that a favorable outcome occurs in nearly every patient who receives the treatment and in few patients in a comparison group . Although NNTs close to 1 are theoretically possible , they are almost never found in practice . However , small NNTs do occur in some therapeutic trials , such as those comparing antibiotics with placebo in the eradication of Helicobacter pylori infection or those examining the use of insecticide for head lice ( Table 2 ) . An NNT of 2 or 3 indicates that a treatment is quite effective . In contrast , such prophylactic interventions as adding aspirin to streptokinase to reduce 5-week vascular mortality rates after myocardial infa rct ion may have NNTs as high as 20 to 40 and still be considered clinical ly effective . Limitations of the Number Needed To Treat Although NNTs are powerful instruments for interpreting clinical effects , they also have important limitations . First , an NNT is generally expressed as a single number , which is known as its point estimate . As with all experimental measurements , however , the true value of the NNT can be higher or lower than the point estimate determined through clinical studies . The 95 % CIs of the NNT are useful in this regard because they provide an indication that Background : Alverine citrate has been used in the treatment of irritable bowel syndrome for many years 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 . To evaluate the efficacy of otilonium bromide , a spasmolytic agent , in the treatment of irritable bowel syndrome using modern and vali date d diagnostic criteria BACKGROUND & AIMS Irritable bowel syndrome ( IBS ) is subtyped as IBS with diarrhea ( IBS-D ) or IBS with constipation ( IBS-C ) based on Rome II guidelines . The remaining group is considered as having mixed IBS ( IBS-M ) . There is no st and ard definition of an alternator ( IBS-A ) , in which bowel habit changes over time . Our aim was to use Rome II criteria to prospect ively assess change in bowel habit for more than 1 year to underst and IBS-A. METHODS Female patients ( n=317 ) with IBS entering a National Institutes of Health treatment trial were studied at baseline with question naires and 2-week daily diary cards of pain and stool frequency and consistency . Studies were repeated at the end of treatment ( 3 months ) and at four 3-month intervals for one more year . Algorithms to classify subjects into IBS-D , IBS-C , and IBS-M groups used diary card information and modified Rome II definitions . Changes in bowel habit at 3-month intervals were then assessed using these surrogate diary card measures . RESULTS At baseline , 36 % had IBS-D , 31 % IBS-M , and 34 % IBS-C. Except for stool frequency , there were no differences between groups . While the proportion of subjects in each subgroup remained the same over the year , most individuals ( more than 75 % ) changed to either of the other 2 subtypes at least once . IBS-M was the least stable ( 50 % changed out by 12 weeks ) . Patients were more likely to transition between IBS-M and IBS-C than between IBS-D and IBS-M. Notably , only 29 % switched between the IBS-D and IBS-C subtypes over the year . CONCLUSIONS While the proportion of subjects in each of the IBS subtypes stays the same , individuals commonly transition between subtypes , particularly between IBS-M and IBS-C. We recommend that IBS-A be defined as at least one change between IBS-D and IBS-C by Rome II criteria over a 1-year period BACKGROUND AND OBJECTIVE The determinants of the placebo effect are not well established . Goal of this study was to explore likely predictive factors in an already published data set . METHODS We re-analysed data from a study in 120 patients with the irritable bowel syndrome ( IBS ) that were r and omly assigned to three arms of the study to receive ( double-blind ) either a drug ( mebeverin ) ( n = 40 ) or placebo ( n = 40 ) , or ( in an open trial ) dietary treatment ( fibre ) ( n = 40 ) for up to 16 week . Treatment was conducted by 3 different doctors ( A , B , C ) with 44 , 27 , and 18 patients , resp . A fourth group ( n = 31 ) was treated by different varying physicians . Symptoms were assessed every 4 weeks , and the degree of patient compliance and the number of drop-outs , the number of patients improved/not improved ( in % ) , symptom severity ( Kruis Score ) at enrolment , and age and gender as covariates were included into the analysis . RESULTS Drop-out rate was 30 % for placebo , 30 % for mebeverin , and 15 % for the diet . For the patients remaining in the study , average compliance was 75 % with placebo , but 89 % for the drug and 82 % for the diet . Response rates were 39 % for placebo , but 20 % for the drug ; response rate for the diet ( open trial ) was 43 % under all doctors . Response rates for drug and placebo combined were 32 % for doctor A ( female,43 years ) , but 19 % for doctors B and C together ( both males , 32 and 40 years ) ) ; this effect was not significant . Placebo responders were more often women ( 47 % ) than men ( 28 % ) , while age effects were only found with dietary treatment : responders were younger . Placebo responders had an overall lower Kruis Score than non-responders ( 45 vs 52 points ) , but this was also true for drug ( 52 vs. 62 points ) and diet responders ( 56 vs 68 points ) . CONCLUSION The major factors contributing to the placebo response are the treating physician ( gender , training ) , and the patients gender ( female ) . Patients with lower Kruis score ( more likely non-functionally disordered ) may be prone to higher ( placebo ) response rates OBJECTIVE To compare the sensitivity , precision , and the costs in time of search ing by h and and by MEDLINE to identify r and omized controlled trials ( RCTs ) for systematic review s. DESIGN Nine anesthetic and pain journals were search ed by both MEDLINE and by h and for the years 1970 , 1980 , and 1990 , recording number of publications and time taken to identify r and omized double-blind controlled trials in pain research . RESULTS Thirty-four volumes , containing 5583 full publications ( 24,417 pages ) and 2889 abstract s and letters ( 1755 pages ) were h and search ed ; 142 eligible ( definite RCTs ) full papers and 171 eligible abstract s and letters were identified . The MEDLINE search strategy yielded 274 reports of which 138 were eligible ; 125 of these were full papers , 1 was a letter and 12 were abstract s. Two full papers which were identified by the MEDLINE search strategy were missed by h and search . The overall sensitivity of the MEDLINE search strategy for full papers was 87 % ( [ 125/144 ] x 100 ) with a precision of 52 % ( [ 125/242 ] x 100 ) . This is the best combination of sensitivity and precision reported to date . Abstract s were mostly in supplement issues which were not indexed . Combining the MEDLINE search strategy with selective h and search of abstract s and letters gave a sensitivity of 94 % . CONCLUSIONS H and search of entire journals remains the most accurate method for identification of the eligible reports , but it is the most time-consuming . The MEDLINE search was faster , but it failed to identify at least 13 % of the indexed eligible reports . Ideally , both h and search and MEDLINE should be used . The combination of MEDLINE with h and search restricted to letters and abstract s might be an acceptable alternative for review ers with insufficient funds to support a full h and search process Assessing the quality of r and omized controlled trials ( RCTs ) is important and relatively new . Quality gives us an estimate of the likelihood that the results are a valid estimate of the truth . We present an annotated bibliography of scales and checklists developed to assess quality . Twenty-five scales and nine checklists have been developed to assess quality . The checklists are most useful in providing investigators with guidelines as to what information should be included in reporting RCTs . The scales give readers a quantitative index of the likelihood that the reported methodology and results are free of bias . There are several shortcomings with these scales . Future scale development is likely to be most beneficial if questions common to all trials are assessed , if the scale is easy to use , and if it is developed with sufficient rigor We are indebted to Professor R. C. Wofinden and Dr. J. F. Skone , of the Department of Public Health , for their help in arranging this investigation , and to the medical officers , Dr. J. Twomey , Dr. E. Bowles , and Dr. G. E. P. Lee , for allowing us to study patients under their care . We are particularly grateful to Sister R. A. Hill for her considerable help and to Mr. A. G. Smith for much administrative assistance . Miss E. Duncan ( statistics ) and Dr. A. Raper ( haematology ) gave valuable support . This investigation was aided by a grant from the Research Committee of the United Bristol Hospitals . The results of a study about the mebeverina administered in 45 cases of irritable colon are reported . The clinical and laboratory findings together with the results of colometrography under psychic stimulation , have shown the therapeutic efficacy of the new formulation , specially in irritable colon with abdominal pain . Its tolerance was excellent Three controlled trials were carried out in patients with irritable bowel syndrome to assess the effectiveness of trimebutine in controlling the symptoms of abdominal distension , pain , flatulence , constipation , diarrhoea and dyspepsia . In the first two trials , it was shown that 200 mg trimebutine 3-times daily for 3 days produced rapid relief of symptoms and was significantly ( p less than 0.001 ) more effective than placebo , but not significantly so when the dosage level was halved . In the third trial , the results showed that 200 mg trimebutine 3-times daily for 2 weeks was as effective as 100 mg mebeverine 4-times daily in relieving the major symptoms and in improving motility . No serious side-effects were reported with trimebutine at the dosage used In a double-blind crossover trial of three days duration on each drug , trimebutine in a dose of 200 mg three times daily was significantly more effective than placebo in relieving the symptoms of mild to moderate degrees of spastic colon ( p<0.001 ) . The only side-effect necessitating discontinuation of treatment was one case of vomiting Twenty adult Indian patients suffering from the spastic form of irritable colon , i.e. abdominal pain and constipation , were given trimebutine ( Mebutin ) , 2-phenyl , 2-dimethylamino-n-butyl 3 , 4 , 5-trimethoxybenzoate . Patients were given treatment with 200 mg trimebutine three times daily , or placebo for 4 weeks , and then crossed over . In addition , stool transit times were assessed by the single stool transit time ( SST ) method of Cummings . Results showed a statistical improvement in abdominal pain and constipation with both trimebutine and placebo after 4 weeks , but only with trimebutine after 8 weeks . Single stool transit time was significantly reduced after trimebutine There is no generally accepted treatment in the irritable bowel syndrome ( IBS ) , probably because of a lack of convincing therapeutic trials . In the present study , 120 out patients with IBS participated in a prospect i ve r and omized therapeutic trial . According to a double-blind design , 40 patients received 400 mg/day mebeverine and 40 patients received a placebo . In an open branch of the trial , 40 patients were treated with 15 g/day wheat bran . The effects of treatment on symptoms were noted after 4 , 8 , 12 and 16 weeks of therapy . A significantly superior symptomatic effect of bran in comparison to mebeverine and placebo was demonstrated after 12 weeks , but could not be confirmed at the end of the study . There was no significant difference between the symptomatic effect of mebeverine and placebo . The compliance with the therapy was about 80 % for 4 weeks , but dropped to about 50 % at the end of the trial . This points to a particular difficulty in the management of patients with IBS . The results of this trial suggest that bran and mebeverine are no ideal therapy for patients with IBS but they support the therapeutic use of bran in patients with IBS |
12,936 | 23,736,885 | Analysis of these motivators reveals that they can be categorized as social and personal benefits .
Social benefits were most frequently described on macroscopic , altruistic levels .
Personal benefits were most frequently psychological in nature .
Rates of participation were compared between the OECD and the non-OECD countries . | An examination of actual HIV vaccine trials can contribute to an underst and ing of motivators for participation in these studies .
Social benefits are generally altruistic , whereas personal benefits are psychological , physical , and financial . | BACKGROUND We conducted a phase I/II r and omized placebo-controlled trial with the aim of exploring whether priming with a low intradermal dose of a multiclade , multigene HIV-1 DNA vaccine could improve the immunogenicity of the same vaccine given intramuscularly prior to boosting with a heterologous HIV-1 MVA among healthy adults in Dar es Salaam , Tanzania . METHODS Sixty HIV-uninfected volunteers were r and omized to receive DNA plasmid vaccine 1 mg intradermally ( i d ) , n=20 , or 3.8 mg intramuscularly ( i m ) , n=20 , or placebo , n=20 , using a needle-free injection device . DNA plasmids encoding HIV-1 genes gp160 subtype A , B , C ; rev B ; p17/p24 gag A , B and Rtmut B were given at weeks 0 , 4 and 12 . Recombinant MVA ( 10(8)pfu ) expressing HIV-1 Env , Gag , Pol of CRF01_AE or placebo was administered i m at month 9 and 21 . RESULTS The vaccines were well tolerated . Two weeks after the third HIV-DNA injection , 22/38 ( 58 % ) vaccinees had IFN-γ ELISpot responses to Gag . Two weeks after the first HIV-MVA boost all 35 ( 100 % ) vaccinees responded to Gag and 31 ( 89 % ) to Env . Two to four weeks after the second HIV-MVA boost , 28/29 ( 97 % ) vaccinees had IFN-γ ELISpot responses , 27 ( 93 % ) to Gag and 23 ( 79 % ) to Env . The id-primed recipients had significantly higher responses to Env than i m recipients . Intracellular cytokine staining for Gag-specific IFN-γ/IL-2 production showed both CD8(+ ) and CD4(+ ) T cell responses . All vaccinees had HIV-specific lymphoproliferative responses . All vaccinees reacted in diagnostic HIV serological tests and 26/29 ( 90 % ) had antibodies against gp160 after the second HIV-MVA boost . Furthermore , while all of 29 vaccinee sera were negative for neutralizing antibodies against clade B , C and CRF01_AE pseudoviruses in the TZM-bl neutralization assay , in a P BMC assay , the response rate ranged from 31 % to 83 % positives , depending upon the clade B or CRF01_AE virus tested . CONCLUSIONS This vaccine approach is safe and highly immunogenic . Low dose , i d HIV-DNA priming elicited higher and broader cell-mediated immune responses to Env after HIV-MVA boost compared to a higher HIV-DNA priming dose given i m . Three HIV-DNA priming immunizations followed by two HIV-MVA boosts efficiently induced Env-antibody responses Abstract Background Evaluating experiences of volunteers in an HIV vaccine trial will be useful for the conduct of future trials . The purpose of this study among volunteers who participated in a phase I/II HIV vaccine trial in Dar es Salaam , Tanzania was to assess what characterized their experiences during the trial . Methods We conducted four focus group discussion s with 35 out of the 60 individuals ( women and men ) after the five scheduled vaccinations . An interpretive description approach was applied to data analysis . Results As a result of the trial interventions , both men and women gained confidence in their own abilities to have safer , less risky sexual behaviour . The participants experienced the trial as a way of accessing free [ insured ] medical services . Most of the men said they had gone from self-medication to professional medical consultation . Despite these benefits , the participants faced various challenges during the trial . Such challenges included mistrust of the trial shown by health care providers who were not connected to the trial and discouragement from friends , colleagues and family members who question ed the safety of the trial . However , they managed to cope with these doubts by using both personal and trial related interventions . Conclusion We found that during the phase I/II HIV vaccine trial , participants had both the opportunities and the ability to cope with the doubts from the surrounding community . Follow up visits enhanced the opportunities and individuals ' abilities to cope with the doubts during the trial . Underst and ing this discourse may be useful for the trial implementers when design ing future trials . Trials Registration IS RCT N : IS RCT N90053831 Pan African Clinical Trials Registry ( PACTR ) : Summary : Underst and ing why people join HIV vaccine efficacy trials is critical for trial recruitment and education efforts . We assessed participants ' motivations for joining the VaxGen VAX004 study , a r and omized , double-blind , placebo-controlled , phase 3 multicenter trial . Of 5417 participants , 94 % were men who have sex with men ( MSM ) and 6 % were women at risk for heterosexual transmission of HIV . Most participants gave altruistic reasons for trial participation : 99 % reported having joined to help find an HIV vaccine , and 98 % reported having joined to help their community . Some gave more personal reasons : 56 % joined to reduce risk behavior and 46 % joined to get protection from HIV . Additional reasons related to receiving services or compensation included to obtain information about HIV ( 75 % ) , to receive free HIV testing ( 34 % ) , and for financial reimbursement ( 14 % ) . Multivariate logistic regression analysis showed that female participants were significantly more motivated than male participants to join the trial for protection and to receive services or compensation ( all P < 0.05 ) . Participants with 13 or more sex partners in the 6 months before enrollment were more likely than those with fewer sex partners to report having joined the trial for protection but less likely to have joined to reduce risk behavior ( both P < 0.05 ) . Because many participants reported personal protection from HIV as their reason for joining , vaccine trial risk-reduction counseling should continue to emphasize the placebo-controlled trial design and unknown efficacy of the test product , particularly for women and persons with large numbers of sex partners . Because a significant minority of participants reported joining to receive HIV information , HIV testing , and financial reimbursement , a need is indicated for provision of HIV prevention services outside research trials and for monitoring to ensure that participants are not motivated to join trials for financial gain Live attenuated viral vectors that express human immunodeficiency virus ( HIV ) antigens are being developed as potential vaccines to prevent HIV infection . The first phase 2 trial with a canarypox vector ( vCP205 , which expresses gp120 , p55 , and protease ) was conducted in 435 volunteers with and without gp120 boosting , to exp and the safety data base and to compare the immunogenicity of the vector in volunteers who were at higher risk with that in volunteers at lower risk for HIV infection . Neutralizing antibodies to the MN strain were stimulated in 94 % of volunteers given vCP205 plus gp120 and in 56 % of volunteers given vCP205 alone . CD8(+ ) cytotoxic T lymphocyte cells developed at some time point in 33 % of volunteers given vCP205 , with or without gp120 . Phase 3 field trials with these or similar vaccines are needed , to determine whether efficacy in preventing HIV infection or in slowing disease progression among vaccinees who become infected is associated with the level and types of immune responses that were induced by the vaccines in this study Behavioral and social issues were investigated in 363 phase I/II preventive HIV-1 vaccine trial volunteers in Thail and . These issues included risk behavior , HIV knowledge , distress , and social consequences of vaccine trial participation . Data were collected at baseline and at 4- , 8- , and 12-month follow-up visits . Volunteers reported relatively low levels of risk behaviors at baseline and at follow-up . Overtly negative reactions from family or friends were reported by 5.9 % . No experiences of discrimination in employment , health care , or insurance were reported . Mean levels of distress were low throughout the trial , and HIV-related knowledge was high , although it was common to consider the possibility of HIV transmission through casual contact . Findings add to the evidence that preventive HIV vaccine trials are feasible in Thail and Objectives : To describe recruitment , screening and baseline characteristics of injection drug users ( IDU ) participating in a phase III HIV vaccine ( AIDSVAX ® B/E ; VaxGen , USA ) trial and to compare enrollment characteristics between trial participants and 1209 IDU from a 1995–1998 vaccine trial preparatory cohort for changes that might impact trial design assumptions . Methods : Enrollment for both studies was conducted at Bangkok narcotic treatment clinics , where a st and ardized question naire was administered on demographics , risk behavior and incarceration history over the previous 6 months . Results : During 1999–2000 , 4943 IDU were screened for enrollment ; successful sources of recruitment included clinic attendees ( 43.4 % ) , an IDU referral program ( 20.4 % ) and preparatory cohort participants ( 14.7 % ) . Of those screened , 1689 ( 34 % ) were HIV seropositive ( HIV subtype B 23.6 % ; subtype E 76.4 % ) . Of the 2545 enrolled , 93.4 % were male . Compared with cohort IDU , trial IDU were younger ( mean age : 28.8 versus 31.3 years ) , better educated ( secondary level or higher : 67.2 % versus 58.7 % ) , and less likely to inject drugs daily ( 39.4 % versus 90.4 % ) ; they were more likely to have been incarcerated ( 78.4 % versus 65.7 % ) , have recently injected stimulants ( 14.8 % versus 5.8 % ) and tranquilizers ( 11.5 % versus 2.3 % ) , and obtained needles/syringes from a source other than a pharmacist ( 7.2 % versus 3.9 % ) ( all P ⩽ 0.003 ) . Conclusions : IDU at high risk for HIV have been successfully enrolled in the AIDSVAX ® B/E efficacy trial . Only minor epidemiologic differences were found at enrollment between trial and preparatory cohort IDU . The latter has proven critical in guiding trial design ; results are expected in late 2003 Objective : To describe recruitment and baseline epidemiologic characteristics of volunteers in the first phase 3 placebo-controlled trial of a recombinant gp120 HIV vaccine ( AIDSVAX B/B ) . Methods : Volunteers were gay/bisexual men or women at risk for sexually transmitted HIV infection . Recruitment strategies , demographics , and risk factors were assessed . HIV status was determined by st and ard HIV-1 antibody assays . Seronegative/viremic HIV infection at enrollment was determined using the HIV-1 nucleic acid test . Results : From June 1998 through October 1999 , 5417 of 7185 volunteers screened were enrolled at 61 sites in the United States , Canada , and The Netherl and s. Successful recruitment methods included distribution of study information at gay venues , advertising and media coverage , and referrals from volunteers . Most volunteers were altruistically motivated , men ( 98 % ) , young ( median , 36 years ) , white ( 83 % ) , well educated ( 61 % college education or more ) , and at high risk for HIV during the 6 months before enrollment . At baseline , 14 were HIV infected ( 12 were seronegative but viremic ; 2 were seropositive and viremic ) . Conclusion : Men and women at high risk for sexually transmitted HIV infection were successfully recruited for the first phase 3 HIV vaccine efficacy trial . Knowledge of recruitment and baseline epidemiologic characteristics of participants in this trial will provide valuable guidance for design ing and conducting future trials Background : The first multicenter , international National Institutes of Allergy and Infectious Diseases (NIAID)-sponsored HIV vaccine trial took place in Brazil , Haiti , Peru and Trinidad . This r and omized , double-blind , placebo-controlled , phase 2 trial evaluated the safety and immunogenicity of a clade B-derived , live canarypox HIV vaccine , vCP1452 . vCP1452 was administered alone or with a heterologous boost of MN rgp120 glycoprotein . The trial was pivotal in deciding whether these vaccines advanced to phase 3 efficacy trials . Methods : Forty seronegative volunteers per site were r and omized to ALVAC alone , ALVAC plus MN rgp120 , or placebo in a 0 , 1 , 3 , and 6 month schedule . Immunogenicity was assayed by chromium-release cytotoxic T lymphocyte ( CTL ) responses ; interferon-gamma ( IFN-γ ) enzyme-linked immunosorbent spot assays ( ELISpot ) ; lymphocyte proliferation assays ( LPA ) ; neutralization ; and enzyme-linked immunosorbent assays ( ELISA ) . Results : Enrollment and follow-up were excellent . Both vaccines were well tolerated . Neutralizing antibody to the laboratory-adapted MN strain was detected . Cellular immune responses , as measured by CTL , ELISpot , and LPA , did not differ between vaccines and placebos . Conclusions : The observation of disappointing immunogenicity in this and a parallel domestic study has informed future vaccine development . Equally important , challenges to doing an integrated trial across countries , cultures , language s , and differing at-risk population s were overcome . The identification of specific safety , ethical , logistic , and immunological issues in this trial established the foundation for current larger international studies A r and omized , double blind , placebo controlled Phase I trial of a prototype human immunodeficiency virus type 1 ( HIV-1 ) synthetic peptide vaccine was conducted in Bangkok , Thail and , to evaluate the safety and immunogenicity of the vaccine in a population of healthy adults at low risk for HIV infection , and to establish essential infrastructure for future HIV vaccine trials in Thail and . Thirty volunteers ( 25 males ; 5 females ) were recruited and r and omized into 3 groups , receiving 3 intramuscular injections of either 100 micrograms vaccine ( N = 12 ) or 500 micrograms vaccine ( N = 12 ) or alum placebo ( N = 6 ) on weeks 0 , 4 and 25 . The vaccine was well tolerated without any serious adverse effects . HIV-1 specific ELISA responses were detected in 20/24 subjects who received the vaccine , with V3 binding antibody titers ranging from 1:69 to 1:5,041 . HIV-1 ( MN ) specific neutralizing antibody was detected in 19/20 of subjects with detectable HIV-1 specific binding antibody . Neutralization titers ranged from 1:14 to 1:1,294 , which were less than titers observed in HIV-infected subjects . The results of this study indicate that the vaccine was well tolerated , and that the vaccine stimulated anti-HIV humoral immune responses in Thai subjects . The successful undertaking of this first HIV vaccine trial conducted in Thail and provided important preparatory information surrounding volunteer recruitment and motivations , and paves the way for future trials of HIV vaccines in Thail and The purpose of this cross-sectional study was to examine relationships between belief in vaccine receipt , motivations for trial participation , and side effects in phase 1 vaccine trials . Anonymous question naires were completed by 125 active vaccine volunteers at two vaccine evaluation sites . Participants believing they had received the vaccine reported more side effects ( p < .01 ) , were less likely to report knowing someone with HIV/AIDS as a motivation for trial participation ( p < .01 ) , and endorsed greater concern about becoming HIV-infected as motivation for participation ( p < .05 ) . Results indicate that inferences made by trial participants in vaccine trials should be identified and addressed , and that greater efforts for maintaining the blinded nature of vaccine trials and educating trial participants about the meaning of side effects are warranted Data from recruitment and screening for a phase I/II preventive HIV-1 vaccine trial in Thail and were evaluated with respect to correlates of participation at each phase . Correlates included demographic variables , motivation for interest in the trial , and factors related to communication and contact . Participants were recruited at two sites through varied methods . The majority of prescreenees reported altruistic motives for interest in the trial and blood donors emerged as a group that may have been particularly altruistic . Findings indicated site differences in attrition during recruitment and screening , but not in enrollment into the vaccine trial . Blood donation and willingness to be contacted by phone at home were significantly related to making and keeping screening appointments |
12,937 | 22,161,425 | This review has demonstrated the feasibility and some potential benefits of orientation interventions .
There was a low level of evidence suggesting that orientation interventions can reduce distress in patients .
However , most of the other outcomes remain inconclusive ( patient knowledge recall/ satisfaction ) . | BACKGROUND Cancer patients experience distress and anxiety related to their diagnosis , treatment and the unfamiliar cancer centre .
Strategies with the aim of orienting patients to a cancer care facility may improve patient outcomes .
Although meeting patients ' information needs at different stages is important , there is little agreement about the type of information and the timing for information to be given .
Orientation interventions aim to address information needs at the start of a person 's experience with a cancer care facility .
The extent of any benefit of these interventions is unknown .
OBJECTIVES To assess the effects of information interventions which orient patients and their carers/family to a cancer care facility , and to the services available in the facility .
All four trials aim ed to investigate the effects of orientation programs for cancer patients to a cancer facility . | Abstract Objective : To compare chemotherapy given at home with outpatient treatment in terms of colorectal cancer patients ' safety , compliance , use of health services , quality of life , and satisfaction with treatment . Design : R and omised controlled trial . Setting : Large teaching hospital . Participants : 87 patients receiving adjuvant or palliative chemotherapy for colorectal cancer . Interventions : Treatment with fluorouracil ( with or without folinic acid or levamisole ) at outpatient clinic or at home . Main outcome measures : Treatment toxicity ; patients ' compliance with treatment , quality of life , satisfaction with care , and use of health re sources . Results : 42 patients were treated at outpatient clinic and 45 at home . The two groups were balanced in terms of age , sex , site of cancer , and disease stage . Treatment related toxicity was similar in the two groups ( difference 7 % ( 95 % confidence interval −12 % to 26 % ) ) , but there were more voluntary withdrawals from treatment in the outpatient group than in the home group ( 14 % v 2 % , difference 12 % ( 1 % to 24 % ) ) . There were no differences between groups in terms of quality of life scores during and after treatment . Levels of patient satisfaction were higher in the home treatment group , specifically with regard to information received and nursing care . There were no significant differences in use of health services . Conclusions : Home chemotherapy seemed an acceptable and safe alternative to hospital treatment for patients with colorectal cancer that may improve compliance and satisfaction with treatment . What is already known on this topic Home chemotherapy programmes have been proposed as an alternative to hospital treatment However , they are more costly , and there is little evidence on their impact on outcomes such as compliance , quality of life , or use of other health services What this study adds Home chemotherapy was not associated with an increased use of health services such as primary care or emergency departments Home chemotherapy had no effect on patients ' quality of life but increased their compliance with treatment and satisfaction , particularly with regard to nursing care Home chemotherapy seems an acceptable and safe alternative to outpatient treatment that may improve compliance with This quasi-experimental longitudinal study documented the impact of a comprehensive cancer informational intervention using information technology on healthcare service use among individuals newly diagnosed with cancer . Women with breast cancer ( n = 205 ) and men with prostate cancer ( n = 45 ) were recruited within 8 weeks of diagnosis at 4 university teaching hospitals in Montreal , Quebec , Canada . The intervention group ( n = 148 ) received a 1-hour training on information technology use , a CD-ROM on cancer , and a list of reputable cancer-related Web sites . The intervention material was available for a period of 8 weeks . The control group ( n = 102 ) received usual care . Self-reported question naires were completed at T1 ( baseline ) , T2 ( 1 week after intervention ) , and T3 ( 3 months after intervention ) . Using multivariate statistics , the experimental group reported significantly more satisfaction with cancer information received compared to the control group . No significant differences were found between experimental and control groups in their reliance on healthcare services . However , women as opposed to men spent more time with nurses , were more satisfied with cancer information received , and relied more heavily on health services . Future research would explore whether the latter observations reflect genuine sex differences or are more contingent on the specific cancer diagnosis The purpose of this study was to test a brief orientation program for reducing anxiety , depressive symptoms , and overall distress in cancer patients at their initial clinic visit . One hundred and fifty consecutively referred patients seen in an oncology outpatient clinic were r and omly assigned to an intervention or usual care control group . The intervention group received a clinic tour , general information about clinic operations , and a question and answer session with an oncology counselor . Outcome measures included the State-Trait Anxiety Inventory ( STAI ) , the Brief Profile of Mood States ( POMS ) , the Center for Epidemiologic Studies -Depression ( CES-D ) Scale , and an oncology clinic question naire which were administered at the initial clinic visit and follow-up . There were no statistically significant clinical or demographic differences between groups at initial assessment . At follow-up , the intervention group had lower state anxiety , lower overall distress , and fewer patients reporting depressive symptoms . Patients in the intervention group demonstrated significantly more knowledge about clinic operations and greater satisfaction with care . These data provide evidence that anxiety , distress and depressive symptoms can be reduced with an orientation program . This finding has particular relevance in the early stages of diagnosis where patients may suffer symptoms of anxiety and depression The purpose of this study was to evaluate the extent to which a new patient information package ( NPIP ) or a mini version of the same package ( mini-NPIP ) reduces emotional distress and meets the informational needs of patients arriving at a tertiary cancer centre for the first time . A comprehensive package , NPIP , consisting of procedural information regarding cancer centre location , description of the health care team , treatment services , research , educational activities , accommodation and community services provided at the centre ; and a condensed version of the same package , mini-NPIP , were developed . Consecutive patients with newly diagnosed breast , gynaecological , lung and prostate cancer , referred to the centre for the first time were prer and omised to receive NPIP , mini-NPIP or no information package . Patients r and omised to NPIP or mini-NPIP were mailed the information package at least one week before their first appointment . On arrival at the centre , patients were administered the Brief Symptom Inventory ( BSI ) which measures psychological distress , and interviewed regarding preferences for information and acceptability of the information packages . Of 465 r and omised patients , 161 were excluded post-r and omisation and 304 completed the entire interview : 100 were r and omised to the NPIP , 102 to the mini-NPIP and 102 to the control group . Emotional distress as measured by the BSI was similar for all groups ( P = 0.98 ) . Most patients preferred to receive the information ( 98 % ) , receive it before the first appointment ( 84 % ) and by mail ( 79 % ) . These preferences were more evident for those given the information packages . The majority of patients found the information packages easy to underst and ( 88 % ) and useful ( 89 % ) , and no differences were detected between packages . The cost of production and dissemination of NPIP was more than double the cost for mini-NPIP : $ 8.93 vs $ 3.98 ( Canadian dollars ) per patient . For patients presenting to a cancer centre for the first time , packages of procedural information do not appear to reduce psychological distress , but are preferred by patients . Given the cost of producing NPIP , mini-NPIP is the preferred approach Abstract Objective : To compare the use and effect of a computer based information system for cancer patients that is personalised using each patient 's medical record with a system providing only general information and with information provided in booklets . Design : R and omised trial with three groups . Data collected at start of radiotherapy , one week later ( when information provided ) , three weeks later , and three months later . Participants : 525 patients started radical radiotherapy ; 438 completed follow up . Interventions : Two groups were offered information via computer ( personalised or general information , or both ) with open access to computer thereafter ; the third group was offered a selection of information booklets . Outcomes : Patients ' views and preferences , use of computer and information , and psychological status ; doctors ' perceptions ; cost of interventions . Results : More patients offered the personalised information said that they had learnt something new , thought the information was relevant , used the computer again , and showed their computer printouts to others . There were no major differences in doctors ' perceptions of patients . More of the general computer group were anxious at three months . With an electronic patient record system , in the long run the personalised information system would cost no more than the general system . Full access to booklets cost twice as much as the general system . Conclusions : Patients preferred computer systems that provided information from their medical records to systems that just provided general information . This has implication s for the design and implementation of electronic patient record systems and reliance on general sources of patient information The primary objective of this study was to test whether specific information given prior to surgery can help patients obtain better pain relief after total knee arthroplasty ( TKA ) . Secondary objectives were to study the impact of preoperative information on state and trait anxiety , satisfaction with pain management and satisfaction with nursing care . The study was an intervention study with two groups of equal size ( n=30 ) . The intervention group was given specific information while the control group received routine information . Pain assessment s were made preoperatively and every 3h for the first three postoperative days , using the visual analogue scale ( VAS ) . The results of this study suggest that information does influence the experience of pain after surgery and related psychological factors . The postoperative pain declined more rapidly for patients in the treatment group , the degree of preoperative state anxiety was lower and they were more satisfied with the postoperative pain management Goals of workBased on meta-analyses regarding the preparation of patients for potentially threatening medical procedures , a DVD , incorporating behavioral role modelling , was developed to prepare patients for chemotherapy and assist them to self-manage side effects . It was hypothesized that patients who watched the DVD ( vs those who did not ) would report ( 1 ) lower anxiety ; ( 2 ) higher self-efficacy related to coping with treatment side effects ; ( 3 ) fewer supportive care needs ; and ( 4 ) higher satisfaction with information received . It was further hypothesized that these effects would be stronger in those perceiving their treatment intent to be curative rather than palliative . Material s and methods Quasi-experimental design using a historical control group was employed . Participants were scheduled to receive their first ever chemotherapy treatment . Group 1 ( usual care ; n = 50 ) was prospect ively recruited before the release of the DVD and group 2 ( DVD plus usual care ; n = 50 ) after the release . Before commencing chemotherapy , all patients completed reliable and valid measures of self-efficacy , anxiety , and supportive care needs . Data was stratified according to perceived treatment intent . Independent sample t tests were performed for each group ( curative vs palliative).Main results Significant differences were found between the usual care and intervention groups : for self-perceived curative patients in relation to self-efficacy for seeking social support ( p = 0.044 ) , with increased confidence in those watching the DVD , and for self-perceived palliative patients in relation to their satisfaction with information about side effects ( p = 0.026 ) , with increased satisfaction in those watching the DVD . Overall , significant differences were found between self-perceived curative vs palliative patients on measures of self-efficacy and supportive care needs , with self-perceived curative patients reporting more confidence and fewer needs . Conclusions The educational DVD was considered highly acceptable by patients and was found to increase self-efficacy and reduce supportive care needs . Hence , it is appropriate to give to patients before face-to-face chemotherapy education . Additional pretreatment education is recommended , particularly for self-perceived palliative patients , to reduce their pretreatment anxiety and enhance their confidence in coping with treatment AIM The aim of this project was to produce audiovisual patient information , which was user friendly and fit for purpose . The purpose of the audiovisual patient information is to inform patients about r and omized controlled trials , as a supplement to their trial-specific written information sheet . BACKGROUND Audiovisual patient information is known to be an effective way of informing patients about treatment . User involvement is also recognized as being important in the development of service provision . The aim of this paper is ( i ) to describe and discuss the process of developing the audiovisual patient information and ( ii ) to highlight the challenges and opportunities , thereby identifying implication s for practice . A future study will test the effectiveness of the audiovisual patient information in the cancer clinical trial setting . METHODS An advisory group was set up to oversee the project and provide guidance in relation to information content , level and delivery . An expert panel of two patients provided additional guidance and a dedicated operational team dealt with the logistics of the project including : ethics ; finance ; scriptwriting ; filming ; editing and intellectual property rights . RESULTS Challenges included the limitations of filming in a busy clinical environment , restricted technical and financial re sources , ethical needs and issues around copyright . There were , however , substantial opportunities that included utilizing creative skills , meaningfully involving patients , teamworking and mutual appreciation of clinical , multidisciplinary and technical expertise . CONCLUSION Developing audiovisual patient information is an important area for nurses to be involved with . However , this must be performed within the context of the multiprofessional team . Teamworking , including patient involvement , is crucial as a wide variety of expertise is required . RELEVANCE TO CLINICAL PRACTICE Many aspects of the process are transferable and will provide information and guidance for nurses , regardless of specialty , considering developing this format of patient information This study tested the efficacy of a pilot orientation program in reducing distress levels of patients with newly diagnosed cancer . Thirty-three consecutive patients were r and omly assigned to an intervention or to a usual-care control group . The intervention group received a clinic tour , general information , and the opportunity to pose questions to an oncology counselor . The dependent variables were measured by the Profile of Mood States-Short Form-Total Mood Disturbance Scale and the State Trait Anxiety Inventory . Scores on the dependent measures were significantly lower in the intervention group . These results suggest that a simple orientation can greatly benefit patients with newly diagnosed cancer . The orientation may reduce anxiety and overall distress by helping patients manage novelty and unpredictability in the unfamiliar clinic setting . This intervention can be delivered within the context of a busy hematology/oncology outpatient clinic Targeted treatment education for cancer patients has the potential to promote adjustment through assisting patients to participate in treatment decision making , comply with treatment regimens and cope more effectively with treatment side effects . A quasi-experimental longitudinal pre-test post-test and follow-up design was used to assess the effect of a patient education video about radiation therapy on patients ' psychological distress , knowledge about radiation therapy , self-efficacy about coping with treatment and physical symptoms . Patients with head and neck ( n=26 ) and breast cancer ( n=66 ) were recruited into the study and allocated into control and intervention groups . No significant differences were found between the control and intervention groups on any of the outcome variables . However , patients in the intervention group reported high levels of satisfaction with the video and all reported that they would recommend the video to other patients preparing for radiation therapy . As well , 90 % of patients in the intervention group reported that some or all of the information in the video was new to them . Education material s that have excellent face validity and that are well received by patients may fail to produce significant change using st and ard controlled study design s. Future research in this area may need to consider alternative paradigms for evaluating the helpfulness of such material BACKGROUND High levels of distress and need for self-care information by patients commencing chemotherapy suggest that current prechemotherapy education is suboptimal . We conducted a r and omised , controlled trial of a prechemotherapy education intervention ( ChemoEd ) to assess impact on patient distress , treatment-related concerns , and the prevalence and severity of and bother caused by six chemotherapy side-effects . PATIENTS AND METHODS One hundred and ninety-two breast , gastrointestinal , and haematologic cancer patients were recruited before the trial closing prematurely ( original target 352 ) . ChemoEd patients received a DVD , question -prompt list , self-care information , an education consultation≥24 h before first treatment ( intervention 1 ) , telephone follow-up 48 h after first treatment ( intervention 2 ) , and a face-to-face review immediately before second treatment ( intervention 3 ) . Patient outcomes were measured at baseline ( T1 : pre-education ) and immediately preceding treatment cycles 1 ( T2 ) and 3 ( T3 ) . RESULTS ChemoEd did not significantly reduce patient distress . However , a significant decrease in sensory/psychological ( P=0.027 ) and procedural ( P=0.03 ) concerns , as well as prevalence and severity of and bother due to vomiting ( all P=0.001 ) , were observed at T3 . In addition , subgroup analysis of patients with elevated distress at T1 indicated a significant decrease ( P=0.035 ) at T2 but not at T3 ( P=0.055 ) in ChemoEd patients . CONCLUSIONS ChemoEd holds promise to improve patient treatment-related concerns and some physical/psychological outcomes ; however , further research is required on more diverse patient population s to ensure generalisability Sixty cancer chemotherapy patients were r and omly assigned to one of four treatments : ( a ) relaxation training with guided relaxation imagery ( RT ) , ( b ) general coping preparation package ( PREP ) , ( c ) both RT and PREP , or ( d ) routine clinic treatment only . All patients were assessed on self-report , nurse observation , family observation , and physiological measures and were followed for five sequential chemotherapy treatments . Results indicate that the PREP intervention increased patients ' knowledge of the disease and its treatment , reduced anticipatory side effects , reduced negative affect , and improved general coping . RT patients showed some decrease in negative affect and vomiting , but not as great as in past studies . The data suggest that a relatively simple , one-session coping preparation intervention can reduce many different types of distress associated with cancer chemotherapy and may be more effective than often-used behavioral relaxation procedures PURPOSE / OBJECTIVES To determine which method of delivery of a cancer orientation program contributed to higher levels of satisfaction and lower levels of anxiety for newly diagnosed patients with cancer and each patient 's support person . DESIGN A r and omized study of patients with cancer and caregivers into one of three delivery methods for an orientation program or a control arm . SETTING A National Cancer Institute- design ated comprehensive cancer center in the midwestern United States . SAMPLE Newly registered patients with cancer diagnoses and their identified support people . METHODS The intervention consisted of an orientation video and booklet delivered by three separate methods : class , drop-in sessions , or information mailed to homes . Participants completed question naires before the intervention and three weeks after the intervention . MAIN RESEARCH VARIABLES State and trait anxiety , satisfaction , underst and ing of the organization , awareness and use of re sources , and stress and coping . FINDINGS The most successful accrual arms were the mailed intervention and control groups . The mailed intervention group compared to the control group reported higher levels of satisfaction with the cancer center , satisfaction with re sources , underst and ing of the cancer center 's structure , and satisfaction with healthcare professionals ' communication with them . Fewer intervention group participants reported a lack of awareness of specific re sources , and a larger percentage of the intervention group used available re sources . Fewer benefits were noted with caregivers . CONCLUSIONS The mailed intervention was successful in improving several patient outcomes . It was shown to be especially helpful to those with high trait anxiety . IMPLICATION S FOR NURSING A mailed orientation program can be a useful approach for increasing satisfaction with services |
12,938 | 15,106,149 | REVIEW ERS ' CONCLUSIONS ITNs are highly effective in reducing childhood mortality and morbidity from malaria . | BACKGROUND Malaria is an important cause of illness and death in many parts of the world , especially in sub-Saharan Africa .
There has been a renewed emphasis on preventive measures at community and individual levels .
Insecticide-treated nets ( ITNs ) are the most prominent malaria preventive measure for large-scale deployment in highly endemic areas .
OBJECTIVES To assess the impact of insecticide-treated bed nets or curtains on mortality , malarial illness ( life-threatening and mild ) , malaria parasitaemia , anaemia , and spleen rates . | The effect of permethrin-treated wall cloths ( Mbu cloth ) on malaria parasitaemia prevalences and malaria morbidity , was evaluated in a population of over 10,000 for a period of three years in the Marigat area , Baringo District , Kenya . The use of the treated cloth in 2,000 houses result ed in significantly lower rates of malaria parasite prevalences with an overall reduction rate of 73 % ( P < 0.001 ) in the treated area . Control areas had an initial increase in rate of malaria parasite prevalence of 30 % and later a reduction of 31 % . There was a slight reduction in spleen rates in the control and treated areas but it was not significant for either between the surveys or among the villages Abstract Objective : To assess the impact of a social marketing programme for distributing nets treated with insecticide on malarial parasitaemia and anaemia in very young children in an area of high malaria transmission . Design : Community cross sectional study . Annual , cross sectional data were collected at the beginning of the social marketing campaign ( 1997 ) and the subsequent two years . Net ownership and other risk and confounding factors were assessed with a question naire . Blood sample s were taken from the children to assess prevalence of parasitaemia and haemoglobin levels . Setting : 18 villages in the Kilombero and Ulanga districts of southwestern Tanzania . Participants : A r and om sample of children aged under 2 years . Main outcome measures : The presence of any parasitaemia in the peripheral blood sample and the presence of anaemia ( classified as a haemoglobin level of ≤80 g/l ) . Results : Ownership of nets increased rapidly ( treated or not treated nets : from 58 % to 83 % ; treated nets : from 10 % to 61 % ) . The mean haemoglobin level rose from 80 g/l to 89 g/l in the study children in the successive surveys . Overall , the prevalence of anaemia in the study population decreased from 49 % to 26 % in the two years studied . Treated nets had a protective efficacy of 62 % ( 95 % confidence interval 38 % to 77 % ) on the prevalence of parasitaemia and of 63 % ( 27 % to 82 % ) on anaemia . Conclusions : These results show that nets treated with insecticide have a substantial impact on morbidity when distributed in a public health setting Malaria vector mosquitoes belonging to the Anopheles gambiae complex were studied in four hamlets in The Gambia . All inhabitants were given bednets treated either with a placebo ( milk ) in two hamlets or with the pyrethroid insecticide permethrin ( 500 mg/m2 ) in two other hamlets . Malaria transmission occurred mainly during a few weeks of the rainy season , in September and October 1987 . The indoor resting densities of mosquitoes in permethrin-treated hamlets were reduced , and we estimated over 90 % reduction in biting on man by An . gambiae Giles sensu stricto in these hamlets . No mosquitoes were found under permethrin-treated bednets compared with eighty-one recovered from placebo-treated bednets . Mosquitoes exited more readily from rooms where permethrin-treated bednets were used than from rooms with placebo-treated nets . The annual mean probability that a child would receive an infective bite was estimated to be 0.09 in hamlets with insecticide-treated bednets , compared with 1.9 where placebo-treated bednets were used . Permethrin-treated bednets are therefore recommended as a means of effectively reducing the risk of exposure to malaria transmission , particularly in areas of low seasonal transmission BACKGROUND Malaria remains a major cause of mortality and morbidity in Africa . Many approaches to malaria control involve reducing the chances of infection but little is known of the relations between parasite exposure and the development of effective clinical immunity so the long-term effect of such approaches to control on the pattern and frequency of malaria can not be predicted . METHODS We have prospect ively recorded paediatric admissions with severe malaria over three to five years from five discrete communities in The Gambia and Kenya . Demographic analysis of the communities exposed to disease risk allowed the estimation of age-specific rates for severe malaria . Within each community the exposure to Plasmodium falciparum infection was determined through repeated parasitological and serological surveys among children and infants . We used acute respiratory-tract infections ( ARI ) as a comparison . FINDINGS 3556 malaria admissions were recorded for the five sites . Marked differences were observed in age , clinical spectrum and rates of severe malaria between the five sites . Paradoxically , the risks of severe disease in childhood were lowest among population s with the highest transmission intensities , and the highest disease risks were observed among population s exposed to low-to-moderate intensities of transmission . For severe malaria , for example , admission rates ( per 1000 per year ) for children up to their 10th birthday were estimated as 3.9 , 25.8 , 25.9 , 16.7 , and 18.0 in the five communities ; the forces of infection estimated for those communities ( new infections per infant per month ) were 0.001 , 0.034 , 0.050 , 0.093 , and 0.176 , respectively . Similar trends were noted for cerebral malaria and for severe malaria anaemia but not for ARI . Mean age of disease decreased with increasing transmission intensity . INTERPRETATION We propose that a critical determinant of life-time disease risk is the ability to develop clinical immunity early in life during a period when other protective mechanisms may operate . In highly endemic areas measures which reduce parasite transmission , and thus immunity , may lead to a change in both the clinical spectrum of severe disease and the overall burden of severe malaria morbidity The malaria incidence and prevalence rates among children who slept under permethrin-impregnated mosquito nets in four villages near Madang , Papua New Guinea , were compared with the rates among children who slept under unimpregnated nets in four paired control villages . Immediately following a parasitological survey in the eight villages , malaria parasites were cleared from the children with chemotherapy , and the mosquito nets in the four experimental villages were impregnated with permethrin . Follow-up parasitological surveys were performed 4 and 10 weeks later . Sporozoite rates in female mosquitos of the Anopheles punctulatus complex decreased significantly in two of the experimental villages after impregnation . Also , the incidence of Plasmodium falciparum between the 4-week and 10-week surveys was significantly lower among the 0 - 4-year olds in villages with impregnated nets than in those with unimpregnated nets , leading to reduced prevalence of P. falciparum in this age group . Use of permethrin-impregnated nets had no effect on the incidence or prevalence of P. falciparum among 5 - 9-year olds or on that of P. vivax among the 0 - 4- or 5 - 9-year olds A group-r and omized controlled trial of insecticide (permethrin)-treated bed nets ( ITNs ) was conducted in an area of high perennial malaria transmission in western Kenya to test the effect of ITNs on all-cause mortality in children 1 - 59 months of age . Child deaths were monitored over a two-year period by biannual household census in Asembo ( 1997 - 1998 ) and in Gem ( 1998 - 1999 ) . Overall , 1,722 deaths occurred in children 1 - 59 months followed for 35,932 child-years . Crude mortality rates/1,000 child-years were 51.9 versus 43.9 in control and ITN villages in children 1 - 59 months old . The protective efficacy ( PE ) ( 95 % confidence interval ) adjusted for age , study year , study site , and season was 16 % ( 6 - 25 % ) . Corresponding figures in 1 - 11- and 12 - 59-month-old children in control and ITN villages were 133.3 versus 102.3 , PE = 23 % ( 11 - 34 % ) and 31.1 versus 28.7 , PE = 7 % ( -6 - 19 % ) . The numbers of lives saved/1,000 child-years were 8 , 31 , and 2 for the groups 1 - 59 , 1 - 11 , and 12 - 59 months old , respectively . Stratified analysis by time to insecticide re-treatment showed that the PE of ITNs re-treated per study protocol ( every six months ) was 20 % ( 10 - 29 % ) , overall and 26 % ( 12 - 37 % ) and 14 % ( -1 - 26 % ) in 1 - 11- and 12 - 59-month-old children , respectively . ITNs prevent approximately one in four infant deaths in areas of intense perennial malaria transmission , but their efficacy is compromised if re-treatment is delayed beyond six months Spatial analyses of the effect of insecticide (permethrin)-treated bed nets ( ITNs ) on nearby households both with and without ITNs was performed in the context of a large-scale , group-r and omized , controlled mortality trial in Asembo , western Kenya . Results illustrate a protective effect of ITNs on compounds lacking ITNs located within 300 meters of compounds with ITNs for child mortality , moderate anemia , high-density parasitemia , and hemoglobin levels . This community effect on nearby compounds without nets is approximately as strong as the effect observed within villages with ITNs . This implies that in areas with intense malaria transmission with high ITN coverage , the primary effect of insecticide-treated nets is via area-wide effects on the mosquito population and not , as commonly supposed , by simple imposition of a physical barrier protecting individuals from biting . The strength of the community effect depended upon the proportion of nearby compounds with treated nets . To maximize their public health impact , high coverage with treated nets is essential The effectiveness of village-wide use of permethrin-impregnated bed nets or eave , window , and door curtains as control measures for Plasmodium falciparum malaria was evaluated during two successive high-transmission seasons in western Kenya . Pairs of villages were assigned to one of three study groups : bed net , curtain , or control . Clinical , parasitologic , and entomologic measures were made from March to July 1990 and again 12 months later . When compared with the controls in 1990 and 1991 , we observed a marked reduction in the incidence of P. falciparum infections in children less than six years old in the bed net villages ( reduced by 40 % and 48 % ) and a smaller but still significant reduction in the curtain villages ( 10 % and 33 % ) . Significant reductions were also seen in the incidence of P. falciparum parasitemias greater than 2,500/mm3 in the bed net group ( reduced by 44 % and 49 % ) and curtain group ( 16 % and 32 % ) . Additionally , we observed significant reductions in the incidence of documented fevers in association with P. falciparum parasitemia in bed net ( reduced by 63 % ) and curtain villages ( 53 % ) when compared with controls . Entomologic inoculation rates in both bed net and control villages decreased by more than 50 % below control values during both high transmission seasons . The results of this study , together with a 1988 study in the same area during the low transmission season , show that bed nets offer greater year-round of protection against P. falciparum infection than curtains . However , during the high transmission season , this technique reduces the frequency of P. falciparum infection rather than preventing it entirely The efficacy of nets treated with lambda-cyhalothrin , a pyrethroid insecticide , on malaria infection and disease was assessed for the first time at the community level in Anopheles gambiae pyrethroid resistance areas . The study was carried out in northern Côte d'Ivoire , which is an area of kdr resistance . Four pairs of villages were selected and matched according to demographic , sociological , and ecological criteria . Among each pair , a village was r and omly allocated to receive mosquito nets . More than 80 % of beds were covered with nets treated with lambda-cyhalothrin and retreated after 6 months . In each village , 54 children aged 0 - 59 months were r and omly selected and clinical ly monitored for 8 periods of 7 days throughout the year . Results showed that the efficacy of treated nets was maintained with a reduction of the prevalence of asymptomatic malaria infection by 12 % and an estimated protective efficacy against malaria disease of 56 % New tools to prevent malaria morbidity and mortality are needed to improve child survival in sub-Saharan Africa . Insecticide treated bednets ( ITBN ) have been shown , in one setting ( The Gambia , West Africa ) , to reduce childhood mortality . To assess the impact of ITBN on child survival under different epidemiological and cultural conditions we conducted a community r and omized , controlled trial of permethrin treated bednets ( 0.5 g/m2 ) among a rural population on the Kenyan Coast . Between 1991 and 1993 continuous community-based demographic surveillance linked to hospital-based in-patient surveillance identified all mortality and severe malaria morbidity events during a 2-year period among a population of over 11000 children under 5 years of age . In July 1993 , 28 r and omly selected communities were issued ITBN , instructed in their use and the nets re-impregnated every 6 months . The remaining 28 communities served as contemporaneous controls for the following 2 years , during which continuous demographic and hospital surveillance was maintained until the end of July 1995 . The introduction of ITBN led to significant reductions in childhood mortality ( PE 33 % , CI 7 - 51 % ) and severe , life-threatening malaria among children aged 1 - 59 months ( PE 44 % , CI 19 - 62 ) . These findings confirm the value of ITBN in improving child survival and provide the first evidence of their specific role in reducing severe morbidity from malaria Insecticide treatment of bed nets ( " mosquito nets " ) may be a cheap and acceptable method of reducing the morbidity and mortality caused by malaria . In a rural area of The Gambia , bed nets in villages participating in a primary health-care ( PHC ) scheme were treated with permethrin at the beginning of the malaria transmission season . Additionally , children aged 6 months to 5 years were r and omised to receive weekly either chemoprophylaxis with maloprim or a placebo throughout the malaria transmission season . We measured mortality in children in PHC villages before and after the interventions described , and compared this with mortality in villages where no interventions occurred ( non-PHC villages ) . About 92 % of children in PHC villages slept under insecticide-treated bed nets . In the year before intervention , mortality in children aged 1 - 4 years was lower in non-PHC villages . After intervention , the overall mortality and mortality attributable to malaria of children aged 1 - 4 in the intervention villages was 37 % and 30 % , respectively , of that in the non-PHC villages . Among children who slept under treated nets , we found no evidence of an additional benefit of chemoprophylaxis in preventing deaths . Insecticide-treated bed nets are simple to introduce and can reduce mortality from malaria Studies on the protective efficacy of insecticide-treated material s ( ITMs ) in Plasmodium vivax endemic areas of Latin America have not yielded sufficient evidence for recommendation of their extensive use in the region . Therefore 2 r and omized community trials have been conducted on the Pacific Coast of Nicaragua which analysed the minimum coverage of ITMs needed to be effective against malaria . For the characterization of the study area , epidemiological and entomological baseline surveys and household interview surveys were undertaken . Thereafter the communities were paired ( 6 pairs in the 1st year and 13 pairs in the 2nd year ) according to 4-monthly reported malaria incidence rates , population size and bednet coverage , and then r and omly allocated to intervention and control groups . In the intervention groups , bednets were impregnated with lambdacyhalothrin ; in the control groups , people received general health education . Anopheles albimanus was found to be the main vector with marked indoor biting behaviour late in the evening . P. vivax ( 99 % ) clearly outweighed P. falciparum ( 1 % ) with low parasite prevalence rates in the asymptomatic general population ( 8 % ) and low parasite densities . The protective efficacy of ITMs varied according to the coverage achieved : protective efficacy was 68 % in communities with an average ITM coverage of 50 % ( 10 pairs ) ; 31 % in communities with an ITM coverage of 16 - 30 % ( 4 pairs ) ; and no protective efficacy in communities with ITM coverage below 16 % ( 5 pairs ) . The comparison with other P. vivax endemic areas in Latin America showed that the vector 's late biting behaviour and the indoor preference ( where ITMs have a repellent effect ) probably led to the favourable results in the study . In malaria endemic areas of Latin America , where P. vivax is predominant , studies on vector behaviour should be conducted in order to predict the impact of ITMs on malaria transmission Insecticide-impregnated bed nets act as a physical barrier to repel and kill mosquitos . Community intervention trials suggest that these nets are effective in preventing malaria-related mortality and morbidity -- but not malaria infection -- in areas of low and moderate transmission ; the results from areas of high transmission are not so encouraging . Comparison of the results from these trials and their interpretation are difficult because of variations in the epidemiology of malaria and several method ological flaws . Problems such as defining appropriate health indicators , monitoring bed-net usage , introducing bed nets r and omly , selecting adequate controls , performing statistical analysis , and comparing bed nets with other available interventions are considered . Further community intervention trials are needed , paying attention to the methods and to assessment of their impact on malaria The effectiveness of insecticide-treated bednets ( ITBN ) in preventing malaria and anaemia among primigravidae living in Kilifi District , Kenya , was assessed by a r and omized controlled trial between September 1994 and November 1995 . All residents within 28 community clusters received ITBN in July 1993 , whilst residents of another 28 clusters served as contemporaneous controls . All resident primigravid women with singleton pregnancies attending antenatal care at Kilifi District Hospital were eligible for recruitment . 503 primigravidae were recruited . 91.4 % were anaemic antenatally ( Hb < 11 g/dl ) : 91.0 % from the intervention arm and 92.0 % from the control arm . Severe anaemia ( Hb < 7 g/dl ) was found among 15.1 % of intervention women and 20.1 % of control women ( P = 0.28 ) . No significant differences were observed in reports of febrile illness or the presence of chloroquine in the serum or peripheral parasitaemia during the third trimester between the two groups . In the women delivering in hospital ( n = 130 ) , there was no association between placental malaria infection and the intervention : 77.4 % of placentas from control women had evidence of past or active infection , compared with 72.0 % of placentas from intervention women ( P = 0.76 ) . Similarly , in the women delivering in hospital , ITBN did not improve birth weight , and there were no differences in perinatal mortality between the two study groups . Despite ITBN having a great impact on paediatric severe malaria and mortality in this transmission setting , there was very little impact of ITBN on the morbidity associated with malaria infection in primigravidae . Alternative strategies are required to tackle this continued public health problem for pregnant women living in endemic areas similar to the Kenyan Coast BACKGROUND The published literature on cluster r and omized trials focuses on outcomes that are either continuous or binary . In many trials , the outcome is an incidence rate , such as mortality , based on person-years data . In this paper we review methods for the analysis of such data in cluster r and omized trials and present some simple approaches . METHODS We discuss the choice of the measure of intervention effect and present methods for confidence interval estimation and hypothesis testing which are conceptually simple and easy to perform using st and ard statistical software . The method proposed for hypothesis testing applies a t-test to cluster observations . To control confounding , a Poisson regression model is fitted to the data incorporating all covariates except intervention status , and the analysis is carried out on the residuals from this model . The methods are presented for unpaired data , and extensions to paired or stratified clusters are outlined . RESULTS The methods are evaluated by simulation and illustrated by application to data from a trial of the effect of insecticide-impregnated bednets on child mortality . CONCLUSIONS The techniques provide a straightforward approach to the analysis of incidence rates in cluster r and omized trials . Both the unadjusted analysis and the analysis adjusting for confounders are shown to be robust , even for very small numbers of clusters , in situations that are likely to arise in r and omized trials An evaluation of the Gambian national insecticide bed net programme , which has introduced insecticide treatment of bed nets into all primary health care ( PHC ) villages in The Gambia , provided an opportunity to compare the individual risk of malaria in children who slept under untreated or insecticide-treated bed nets . 2300 children 1 - 4 years old were selected for a survey at the end of the 1992 rainy season , 1500 from PHC villages and 800 from non-PHC villages . All malariometric indices were lower , and the mean packed cell volume was higher , in children who slept regularly under treated or untreated bed nets than in those who did not use a net . This study suggested that untreated bed nets provide some individual protection against malaria , although not as efficiently as that provided by insecticide-treated bed nets which were particularly effective at preventing infections accompanied by high parasitaemia A trial to determine the effectiveness of sisal eaves-curtains impregnated with permethrin for malaria control was conducted in the malaria holoendemic western Kenya between 1991 and 1993 . Indoor resting densities of Anopheles gambiae s.l . and Anopheles funestus were reduced by 90.9 % and 93.8 % respectively in protected houses . The entomological inoculation rate ( EIR ) was reduced by 72 % in the intervention village . There was no significant reduction in vector longevity or survival as shown by the sustained high sporozoite rates . Monthly bioassays for retained insecticidal potency of permethrin on the fibre indicated vector mortality rates above 95 % over the period . Of 283 and 240 children followed up from the intervention and control villages , a mean malaria prevalence of 43.2 % and 52.2 % respectively was observed over the trial period ( p < 0.01 ) . The prevalence rose to 73.5 % and 75.7 % ( p = 0.541 ) respectively after the removal of the curtains . No significant differences were observed in the mean parasite density between the groups or between the proportions with parasite density exceeding 2,500 per microliter and with or without fever . The prevalence of splenomegaly was significantly lower in the intervention group compared to the control , both during ( p = 0.005 ) and after the intervention ( p < 0.001 ) . There was no significant difference in the mean change in haematocrit at the end of the intervention . We observe that permethrin impregnated sisal curtains effectively retain permethrin , alter favourably the indoor vector density and EIR , and could provide a reduction in malaria prevalence A double-blind controlled trial was undertaken from August 1990 to February 1991 among Karen children on the Thai-Burmese border to evaluate the effects on malaria incidence and prevalence of permethrin-treated bed nets . Three hundred and fifty schoolchildren , aged 4 to 15 years , were allocated at r and om to receive either a permethrin-impregnated net or a non-treated net . The incidence of malaria infections , confirmed by a blood film , was assessed during 6 months . Three surveys were conducted , on admission and 3 and 6 months later , to measure the prevalence of infections and spleen rates . Compliance was assessed by monthly home visiting . The use of permethrin-treated bed nets reduced the number of parasitaemic Plasmodium falciparum infections by 38 % and the number of symptomatic episodes by 42 % . The number of P. vivax malaria attacks was similar in each group . The prevalence of positive blood films in the 2 groups did not change significantly during the study . A reduction in spleen rate by 50 % in both groups at the end of the study period could not be related to the overall use of nets . Compliance was high and no side-effect was reported . The long-term effects on morbidity and mortality need to be assessed after distribution of permethrin treated bed nets at the village level We have measured the entomological impact of insecticide treated nets on malaria transmission at Ganvie , a village in the coastal and lagoon area of Benin . The nets we have impregnated belong to the population of this village . Men and women of Ganvie used the nets everyday against nuisance biting . Then , the nets we have impregnated are not experimental nets introduced in the village . We have treated 3,230 nets , that means 79 % of the nets of this village which counts 20,000 inhabitants . After treating the nets , the inoculation rate due to Anopheles gambiae s.s . and A. melas has decreased from 11 to 4.6 infected bites per man/year , that represents 58.5 % of reduction of malaria transmission . We have also observed that the parturity rate of anopheles has decreased from 45.3 to 38.8 % . We are sure that the entomological performances due to the impregnation will increase more if the inhabitants of Ganvie change their behaviours . They must reduce the frequency of impregnated net wash and repair the teared nets An intervention trial was undertaken in a rural area of The Gambia to assess the impact on malaria morbidity of the use of bed nets . Bed nets were allocated at r and om among a group of 16 Fula hamlets , where they were previously rarely used . The incidence of febrile episodes with associated malaria parasitaemias throughout the rainy season and the prevalence of splenomegaly and parasitaemia at the end of the rainy season were determined in 233 children aged 1 - 9 years who slept under bed nets and in 163 children who did not . Bed nets were used correctly by the children in the study cohort , but direct observations showed that a significant number of children left their nets for a period during the night . There was no significant difference in the incidence of clinical attacks of malaria or in any other malariometric measurement between the 2 groups . Thus , bed nets were not effective in reducing malaria morbidity in this group of children . The apparent protection from bed nets demonstrated in previous retrospective surveys may have been due to an increased number of infective bites being received by exposed individuals sleeping close to users of bed nets As part of a community-based , group-r and omized , controlled trial of insecticide-treated bed nets ( ITNs ) in an area with intense malaria transmission in western Kenya , a birth cohort ( n = 833 ) was followed monthly until the age of 24 months to determine the potential beneficial and adverse effects of reduced malaria exposure during pregnancy and infancy . Malaria transmission and morbidity were comparable pre-intervention . The ITNs reduced malaria attack rates ( force of infection ) in infancy by 74 % , and delayed the median time-to-first parasitemia ( 4.5 to 10.7 months ; P < 0.0001 ) . The incidence of both clinical malaria and moderate-severe anemia ( hemoglobin level < 7 g/dL ) were reduced by 60 % ( P < 0.001 for both ) . Protective efficacy was greatest in infants less than three months old and similar in older infants and one-year-old children . Efficacy was lowest in the dry season . Infants from ITN villages experienced better height and weight gain . In areas of intense perennial malaria transmission , ITNs substantially reduce exposure to malaria and subsequent malaria-associated morbidity in children less than 24 months old . Reduced malaria exposure during infancy did not result , with continued ITN use , in increased malaria morbidity in one-year-old children Malaria is prevalent throughout coastal and lowl and Papua New Guinea . Recent changes , including a shift from predominance of Plasmodium vivax to Plasmodium falciparum , appearance of chloroquine-resistant P. falciparum and decreased effectiveness of vector control programs have been observed . Epidemiological features of malaria were studied through four six-month surveys of a population of 16,500 in Madang Province from 1981 - 1983 . Baseline data on parasitology , splenic enlargement , serology , hemoglobin levels , prevalence of 4-aminoquinolines , utilization of mosquito nets and incidence of fever were collected for use in future evaluation of malaria control measures including possible field trials of an antimalarial vaccine . Prevalence of parasitemia ( all species , all ages ) varied from 35.0 % to 42.7 % over the four surveys each of which covered a r and om sample of 25 % of the population . The ratio of parasite species was : P. falciparum 70:P. vivax 25:P. malariae 5 in the dry seasons , shifting slightly in favor of P. falciparum during the wet seasons . Intense year-round transmission was indicated by decreasing parasite prevalence and splenic enlargement with age , low density asymptomatic parasitemias and high prevalence of antimalarial antibodies ( i.e. , greater than 80 % of the population over five years of age was ELISA-positive ) . Levels of endemicity varied geographically , presence of 4-aminoquinolines in urine sample s was relatively common ( 12.7 % positive ) and chloroquine resistance was widespread ( 81.6 % in vitro , 46.6 % in vivo ) One hundred and ninety students aged 6 to 18 at a boarding school 120 km west of Nairobi in the Rift Valley participated in a comparative trial of malaria prophylaxis . Treatment with a combination of amodiaquine 25 mg/kg over three days plus doxycycline 100 mg twice daily for five days cleared their blood of Plasmodium falciparum . They were then r and omly divided into the following three groups matched for age and sex : one group slept under mosquito nets ; one group received one or two tablets ( 100 mg each ) of proguanil hydrochloride daily according to weight ; one group received one or two placebo tablets daily which were the same size and colour as the proguanil tablets . Malaria was diagnosed when asexual P falciparum were seen on blood films and was treated with pyrimethamine-sulphadoxine . At the end of one school term 188 of the 190 students had completed the study . One new infection was found during 3893 days of follow up in the mosquito net group , eight new infections over 3667 days in the proguanil group , and 35 new infections over 3677 days in the placebo group , representing a reduction of 97.3 % and 77.1 % in attack rates for the mosquito net method and for treatment with proguanil respectively . Both provide effective protection from malaria A project testing the efficacy of insecticide (permethrin)-impregnated bed nets , compared with impregnated door and window curtains , residual house spraying , and a control group was implemented in 12 village clusters in the Nsukka Local Government Area of Enugu State , Nigeria , using epidemiologic and entomologic indicators . The appropriate material s and services were given free to all families . During the first year of study , three monitoring exercises were carried out in a r and om selection of homes where children under 5 years of age resided . Information was collected on perceived effectiveness of the interventions , condition of nets and curtains , reasons for not sleeping under nets , and recall of steps required in caring for nets and curtains . Bed nets were perceived as more effective in reducing mosquito bites compared with the two other interventions . At the last monitoring period , which occurred a few weeks before a re-impregnation exercise , respondents also perceived bed nets to be most effective in preventing malaria . These findings coincided with epidemiologic evidence . Curtains , especially those at doors , were more likely to be torn and dirty than bed nets . Although holes would not reduce the effectiveness of the insecticide , they could reduce the ' beauty ' of the curtains , a perceived benefit that initially attracted villagers to both curtains and nets . Bed net owners reported significantly less frequent use of other mosquito control measures in their homes than did members of the other groups . Finally , bed net users demonstrated increased knowledge of use and care steps than did those with curtains . These findings suggested a high level of social acceptability of bed nets , and point to the need to test their acceptability further under conditions where people would pay for nets and communities would manage distribution and re-impregnation systems A prospect i ve comparison of the antimalarial efficacy of bed nets was conducted with 341 pregnant women living in a mesoendemic malarious area of the Thai-Burmese border . Women in 3 adjacent study sites were allocated at r and om to receive either a single size permethrin-impregnated bed net ( PIB ) , a non-impregnated bed net ( NIB ) , or to a control group who used either their own family size non-impregnated bed net ( FNIB ) or no net . In one study site , but not the other 2 , PIB significantly reduced parasite densities and , together with FNIB , reduced the incidence of malaria in pregnancy from 56 % to 33 % ( relative risk = 1.67 , confidence interval = 1.07 - 2.61 , P = 0.03 , allowing for parity ) . Anaemia proved a more sensitive marker of bed net antimalarial efficacy than parasite rates . The incidence of anaemia ( haematocrit < 30 % ) at all study sites was significantly lower at delivery in the PIB ( 27 % ) and FNIB groups ( 21 % ) than in the NIB group ( 41 % ) or those using no net ( 56 % ) . This suggests that a significant proportion of the malaria in pregnancy in this mesoendemic area was sub-patent . Both patent Plasmodium falciparum parasitaemia and anaemia were associated with a reduction in birth weight . Infant mortality was high ( 16 % ) and strongly associated with prematurity , low birth weight and maternal anaemia . PIB were well tolerated and had no apparent adverse effect on the pregnancy or infant development . Although the overall effect of bed nets on patent parasitaemia was marginal , they were associated with a significant reduction in maternal malaria-associated anaemia . ( ABSTRACT TRUNCATED AT 250 WORDS Trials were undertaken in a hypoendemic area of malaria in an area bordering Vietnam , in Napo County of Guangxi Zhuang Autonomous Region , China . The aim was to compare the relative cost effectiveness of DDT residual spraying and of bednets impregnated with deltamethrin in the malaria control program . The trials were divided into three subgroups : ( 1 ) two farming areas and one coal mining area with a total population > 20,000 , where the trial consisted of mass bednets impregnated with deltamethrin 15 mg/m2 net surface once a year , ( 2 ) one farming area with a population of approximately 3,600 where DDT residual spraying at 2g/m2 was carried out twice a year in May and August ; ( 3 ) one farming area and one coal mining village with a population of > 4,000 were used as a control . The malaria vector population consisted mainly of Anopheles minimus and An . anthropophagus with a small contribution from An . sinensis . After bednets were impregnated with deltamethrin the mosquitos resting on the surface of the bednets decreased significantly , although there was less effect on the total vector population . The results showed that malaria incidence decreased significantly both in areas where impregnated bednets were used and in areas where residual spraying was undertaken . The positive IFAT rates of residents who slept under impregnated bednets decreased significantly in farming areas , especially in that area where bednet impregnation as a vector control measure had been undertaken for two years , but there was no change in the IFAT rate in DDT sprayed or control areas . ( ABSTRACT TRUNCATED AT 250 WORDS The aim of many research investigations is to compare the proportion of individuals in each of several groups that have a certain characteristic . The unit of allocation for such investigations is often an intact social unit , as in r and omizing families , medical practice s , schools , or entire communities , to different intervention groups . St and ard statistical methods are not appropriate for these design s , since they do not take into account the dependencies among individuals within the same cluster . The authors review the strengths and weaknesses of several approaches for dealing with this problem , using data from a school-based smoking cessation trial . A principal conclusion is that the choice of method should depend on whether or not r and om allocation is used in the assignment of interventions Insecticide-impregnated bednets appear to be a potentially cost-effective intervention against endemic malaria in the tropics , but this has yet to be confirmed by field trials . There are two aspects to consider in assessing such trials : ( 1 ) the extent to which subjects use nets regularly and properly , and ( 2 ) the effectiveness of nets which are truly used regularly and properly in reducing malaria transmission . The second aspect is currently of primary concern , to determine if human-vector relationships for a particular at-risk population are such that bednets can be effective . But to give bednets a " fair " test in this regard requires regular and proper use in the first place . The study described here suggests they did not get a " fair " test in one field trial in Sabah , East Malaysia . The study also strongly suggests that direct observations , rather than post hoc question ing of subjects , may be essential to accurately gauge bednet usage rates . Accurate usage rates are required to determine what proportion of a population needs to use nets to reduce malaria transmission , and to evaluate the effectiveness of promotional programs over time . Direct observations can also yield valuable data on night-time activities that increase malaria risk , such as television viewing that keeps people awake and out of bednets The effectiveness of permethrin-impregnated ( 0.5 g/m2 ) bed-nets and curtains as malaria control measures was evaluated in Uriri , Kenya in 1988 . One hundred five families were r and omly assigned to 1 of 3 study groups ( control , bed-net , or curtain ) . All participants were cured of parasitemia with pyrimethamine/sulfadoxine . Selective epidemiologic and entomologic parameters were measured weekly , while knowledge , attitude , and practice s surveys were conducted at the beginning and end of the 15 week study . Plasmodium falciparum infections per person week at risk were significantly higher in the control group than in either the curtain group ( 5.42 vs. 2.35 cases/100 person weeks risk ) or the bed-net group ( 5.42 vs. 3.77 cases/100 person weeks risk ) . The curtain group had fewer infections per person week at risk than the bed-net group ( 2.35 vs. 3.77 cases/100 person weeks risk ) . A difference was found in clinical malaria among the groups : 45 % of persons in the bed-net and curtain groups vs. 30 % of those in the control group reported no episodes of fever and chills ( chi 2 , P less than 0.05 ) . Indoor resting Anopheles gambiae or An . funestus were found on 94 occasions in the control houses , but only twice in the treated houses during weekly visits to each house over the study period ( chi 2 P less than 0.001 ) . The pyrethrum knockdown method produced similar results with a total of 195 , 23 , and 3 An . gambiae and An . funestus collected in the control , bed-net , and curtain houses during the same period , respectively . ( ABSTRACT TRUNCATED AT 250 WORDS To evaluate whether insecticide-treated netting ( ITN ) reduces child mortality in different epidemiological setting s , 4 large , r and omized , controlled trials were conducted in Africa . Here we report the findings from the trial in Burkina Faso , in an area of hyperendemic and markedly seasonal malaria transmission . The trial involved 158 villages , with a total population of some 90,000 , grouped into 16 geographical clusters . Ascertainment of mortality among children aged 6 - 59 months began in early 1993 . In June/July 1994 , 8 of the clusters , r and omly selected , received permethrin-treated curtains . Follow-up of children and ascertainment of mortality continued until May 1996 . A 15 % reduction in all-cause mortality among children aged 6 - 59 months was observed over the 2-year period following the installation of the curtains ( 95 % c.i . -4 % to 30 % ) . In the first year , post-intervention mortality was substantially lower in the clusters receiving curtains compared with the control clusters ( rate ratio = 0.74 ; 95 % c.i . 0.57 , 0.95 ) but in the second year , there was no difference between mortality in the two groups ( rate ratio = 0.99 ) . The overall two-year impact of the intervention is consistent with the impacts observed in other trials which have demonstrated reductions in child mortality of from 17 % to 33 % . However , the year-by-year analysis raises some concerns about the long-term effect of ITN . Further follow-up of this population is warranted OBJECTIVES The objective of this study was to produce data indicating whether insecticide-treated bednets should replace insecticide house spraying as a malaria control method in South Africa . We report 2 years of preliminary data on malaria incidence comparing areas receiving insecticide-treated bednets and those subjected to house spraying in northern KwaZulu-Natal . DESIGN , SETTING AND SUBJECTS In order to measure significant reductions in malaria incidence between the two interventions , a geographical information system ( GIS ) was used to identify and create seven pairs of geographical blocks ( areas ) in the malaria high-risk areas of Ndumu and Makanis in Ingwavuma magisterial district , KwaZulu-Natal . Individual blocks were then r and omly allocated to either insecticide-treated bednets or house spraying with deltamethrin . Malaria cases were either routinely recorded by surveillance agents at home or were reported to the nearest health facility . RESULTS AND CONCLUSIONS The results show that 2 years ' use of insecticide-treated bednets by communities in Ndumu and Makanis , KwaZulu-Natal , significantly reduced the malaria incidence both in 1997 ( rate ratio ( RR ) = 0.879 , 95 % confidence interval ( CI ) 0.80 - 0.95 , P = 0.04 ) and in 1998 ( RR = 0.667 , CI 0.61 - 0.72 , P = 0.0001 ) . Using a t-test , these significant reductions were further confirmed by an assessment of the rate of change between 1996 and 1998 , showing a 16 % reduction in malaria incidence in blocks using treated bednets and an increase of 45 % in sprayed areas ( t = 2.534 , P = 0.026 ( 12 df ) ) . In order to decide whether bednets should replace house spraying in South Africa , we need more data on the efficacy of treated bednets , their long-term acceptability and the cost of the two interventions A 17 % efficacy in preventing all-cause mortality in children aged 6 - 59 months was previously reported from a cluster-r and omized controlled trial of insecticide-treated mosquito nets ( ITNs ) carried out in the Kassena-Nankana District of northern Ghana from July 1993-June 1995 . A follow-up until the end of 2000 found no indication in any age group of increased mortality in the ITN group after the end of the r and omized intervention . These results should further encourage the use of ITNs as a malaria control tool in areas of high endemicity of Plasmodium falciparum Of the 20 Anopheles species caught in villages in Sonapur , Assam , only An . minimus was incriminated as a malaria vector by finding sporozoites in the salivary gl and s. It was found to be endophagic and endophilic in Assam and because its biting peaked after midnight it was a suitable target for insecticide impregnated bednets . After the withdrawal of DDT spraying and collecting a year 's baseline data , deltamethrin impregnated nets were distributed in 3 villages , untreated nets were distributed in 6 villages and 3 were held as untreated controls . The population of each of these groups of villages was about 1700 . The nets were well received by the local tribal population . Human l and ing catches with baits unprotected or under partially lifted nets showed that the nets provided a high degree of personal protection against all the local species of human biting mosquito . In addition , there was evidence for suppression of the An . minimus population in a village with treated nets . Malaria was monitored by weekly active surveillance in all the villages . In the untreated control villages the slide positivity rate and monthly parasite index rose significantly during the trial . In the villages with untreated nets , these parameters showed no significant change , but in the villages with treated nets they declined significantly . On the basis of these results , the widespread distribution of impregnated nets was recommended to the state health authorities We compared the anti-mosquito and antimalarial potentialities of placebo-treated versus permethrin-impregnated bed nets in north-western Guinea Bissau . Baseline , pre-intervention entomological and parasitological data were collected during the rainy season of 1990 and bed nets were distributed shortly before the rainy season of 1991 . Pairs of 3 ethnically different villages were investigated . The villages in each pair were at least 2 km apart but belonged to the same ethnic group in an ecologically similar area . After one year permethrin-treated bed nets were provided to all people in one village of each pair and placebo-treated bed nets to the other villages . About 98 % of mosquitoes caught in bedrooms belonged to Anopheles gambiae and A. melas , which we consider to be the main malaria vectors in the study villages . Mean Plasmodium falciparum sporozoite rate in A. gambiae ( 9.6 % ) and A. melas ( 12.4 % ) was highest during October-November . The Plasmodium index in children 2 - 9 years old in the 6 villages , at the end of the rainy season 1990 , ranged between 44 % and 79 % . Of these , 98 % were identified as P. falciparum , 1 % as P. malariae and 1 % as mixed infections of these species . Significant reductions of Anopheles indoor resting densities and malaria parasite rates in humans were recorded in villages which had received permethrin-treated nets , but not in the control villages . The mean number of P. falciparum-infective mosquito bites received indoors in untreated villages during the rainy season was estimated to be about 4 per child and 20 per adult . This inoculation rate was reduced by at least 78 % by the use of permethrin-impregnated bed nets . The malaria parasite rates and proportions of people experiencing ' disease with fever ' decreased significantly in villages provided with permethrin-treated nets but not in the control villages . Impregnated nets may be an important tool to reduce disease and death due to malaria in Guinea Bissau Effects of the distribution in space of permethrin (insecticide)-impregnated bed nets ( IIBNS ) on child mortality were studied in a r and omized controlled trial of IIBNs in a an area highly endemic for Plasmodium falciparum malaria in rural northern Ghana . Eight hundred sixty-two deaths occurred among children 6 - 59 months of age during 16,841 child-years-at-risk . Mortality increased with the distance from health facilities but not with proximity to identifiable anopheline breeding sites ( reservoirs ) . The efficacy of IIBNs was independent of these distances . Mortality in users of IIBNs was independent of the proximity of nonusers , and mortality rates of nonusers and users living close to each other were similar . Poisson regression estimated a 6.7 % increase in mortality among nonusers with each 100-m shift away from the nearest compound with IIBNS , indicating that the insecticide protects nearby nonusers . High coverage of IIBNs achieves maximum impact , but users of IIBNs offer some protection to less fortunate neighbors if coverage is incomplete Insecticide-treated mosquito nets ( ITN ) provide excellent protection against malaria ; however , they have a number of shortcomings that are particularly evident in politically unstable countries or countries at war : not everyone at risk can necessarily afford a net , nets may be difficult to obtain or import , nets may not be suitable for migrants or refugees sleeping under tents or plastic shelter . There is a need to develop cheaper , locally appropriate alternatives for the most impoverished and for victims of complex emergencies . Afghan women , in common with many Muslim peoples of Asia , wear a veil or wrap known as a chaddar to cover the head and upper body . This cloth doubles as a sheet at night , when they are used by both sexes . A r and omized controlled trial was undertaken in which 10 % of the families of an Afghan refugee camp ( population 3950 ) in north-western Pakistan had their chaddars and top-sheets treated with permethrin insecticide at a dosage of 1 g/m2 while a further 10 % had their chaddars treated with placebo formulation . Malaria episodes were recorded by passive case detection at the camp 's health centre . From August to November the odds of having a falciparum or vivax malaria episode were reduced by 64 % in children aged 0 - 10 years and by 38 % in refugees aged < 20 years in the group using permethrin-treated chaddars and top-sheets . Incidence in refugees over 20 years of age was not significantly reduced . The cost of the permethrin treatment per person protected ( US$ 0.17 ) was similar to that for treating bednets ( and cost only 10 - 20 % of the price of a new bednet ) . An entomological study simulating real-life conditions indicated that host-seeking mosquitoes were up to 70 % less successful at feeding on men sleeping under treated chaddars and some were killed by the insecticide . Permethrin-treated top-sheets and blankets should provide appropriate and effective protection from malaria in complex emergencies . In Islamic and non-Islamic countries in Asia , treated chaddars and top-sheets should offer a satisfactory solution for the most vulnerable who can not afford treated nets This study was conducted from January to December 1992 in Kumba , a town situated in the rain forest region of the South-West Province of Cameroon , and consisted of a longitudinal survey including parasitological and clinical studies . Forty households were chosen for the study and r and omly divided into two groups , each with approximately 240 inhabitants aged < or = 15 years . One group received deltamethrin impregnated bednets and the other group had no nets ( control ) . For the months of April , June and August ( rainy season ) , deltamethrin impregnated bednets did not reduce malaria prevalence significantly , but the overall malaria prevalence for all months of the study was significantly reduced ( chi 2 MH = 9.17 , P = 0.002 ) . Enlarged spleen rates ( chi 2 MH = 6.73 , P = 0.009 ) and spleen sizes ( P = 0.0002 ) were also significantly reduced by the nets . However , the reduction in the geometric mean parasite density ( GMPD ) was not significant . Even though some of these reductions were statistically significant , they were relatively low in a global context compared with previous work done mainly in rural areas . In an urban environment , parents and children usually stay up late , and probably receive many mosquito bites before going to sleep Both malaria and undernutrition are major causes of paediatric mortality and morbidity in sub-Saharan Africa . The introduction of insecticide-treated bed nets ( ITBN ) during a r and omized controlled trial on the Kenyan coast significantly reduced severe , life-threatening malaria and all-cause childhood mortality . This paper describes the effects of the intervention upon the nutritional status of infants aged between 1 and 11 months of age . Seven hundred and eighty seven infants who slept under ITBN and 692 contemporaneous control infants , were seen during one of three cross-sectional surveys conducted during a one year period . St and ardized weight-for-age and mid-upper arm circumference measures were significantly higher among infants who used ITBN compared with control infants . Whether these improvements in markers of nutritional status were a direct result of concomitant reductions in clinical malaria episodes remains uncertain . Never-the-less evidence suggests that even moderate increases in weight-for-age scores can significantly reduce the probability of mortality in childhood and ITBN may provide additional gains to child survival beyond their impressive effects upon malaria-specific events Malaria continues to be an increasing health concern in many endemic areas where it remains a major contributor to childhood morbidity and mortality . Chemoprophylaxis and treatment are increasingly compromised by drug resistance . Vaccination for malaria is not yet available outside clinical trials . In clinical trials bed nets have been shown to be effective in reducing malarial morbidity and mortality . Their efficacy outside of the clinical trial setting has been less well documented . We describe our experience with the introduction of bed nets in a remote rural Zambian village and document the effect on malarial parasitaemia , spleen rates and haemoglobin . Children were evaluated at the end of the rainy seasons in April 1998 and April 1999 . Insecticide impregnated nets were made available for purchase to the village in July 1998 . Rates of parasitaemia and anaemia were significantly reduced BACKGROUND Despite gains in malaria control through impregnated treated nets ( ITN ) , malaria remains a major concern . Netting is expensive and impractical for many communities . Here we present the findings of a community-based trial of impregnated bedsheets ( shukas ) in Kenya . METHODS A total of 472 individuals were enrolled in a r and omized community trial where the unit of r and omization was the hamlet ( manyatta ) . Baseline data included socio-demographic data , parasite prevalence data from thick and thin blood smears , and clinical measures of malaria . The intervention involved the dipping of shukas owned by the experimental group in permethrin . FINDINGS The prevalence of malaria in the study population ( based on laboratory results ) was considerably lower than that used for the power calculation based on clinical estimates ( 2.2 % versus 20 % ) . For those aged 6 or over , the rate of malaria cases ( events per 10 000 person-days at risk ) was 1.41 in the experimental group versus 7.49 in the control group ( incidence rate ratio 0.187 , 95 % CI : 0.046- 0.770 ) . For children < /=5 years of age results were imprecise with no clear benefit of the intervention . CONCLUSIONS These results suggest that permethrin-impregnated bedsheets may be protective against malaria prevention but further studies with greater power are required to confirm this Between 1992 and 1995 a series of studies was undertaken to assess the long-term suitability of pyrethroid-impregnated bednets ( PIBs ) for malaria control in Afghan refugee communities in two villages in North-West Frontier Province , Pakistan . During 1992 , 86 % of bednet owners volunteered to have their bednets re-impregnated , and a further 15 % of families purchased nets at two-thirds of cost price . From 1992 onwards , 27 % of the villagers returned to Afghanistan , and annual house spraying campaigns were introduced to protect those still resident but sleeping without bednets . Within 3 years , these campaigns , together with PIBs , reduced the annual incidence of malaria by 87 % , from 597 to 78 cases per 1000 population . Nevertheless , 65 % of resident families continued to re-impregnate their nets annually with permethrin . To assess whether PIBs were still being used and were still protective , in view of these reduced transmission rates , we carried out a case -- control study in 1994 on febrile or otherwise symptomatic patients presenting at village health centres . Comparison of the slide-positivity rates of PIB users and those without bednets showed that regular usage reduced the odds of contracting falciparum and vivax malaria to 0.22 ( 95 % confidence interval ( CI ) : 0.09 - 0.55 ) and 0.31 ( 95 % CI : 0.19 - 0.51 ) , respectively . There was no evidence of a sex- or age-bias in bednet use or in protective effect . The results indicate that a community-based PIB programme is an appropriate malaria control measure in areas where management or security problems make traditional house-spraying campaigns impossible . A relevant finding for those involved in the monitoring of bednet distribution projects is that the local coverage of bednets and the local impact on malaria , even when introduced to remote areas , can be estimated very cheaply by health centre microscopists who simply catalogue blood film diagnoses according to patients ' bednet use practice The effect of community-wide use of bednets treated with lambdacyhalothrin 10 mg/m2 on the malaria vector Anopheles gambiae ( forest form ) was evaluated in Sierra Leone . Sixteen similar villages near the town of Bo were r and omly allocated either to remain without nets or to receive treated bednets for all inhabitants , with effect from June 1992 . Mosquitoes were sample d using human biting catches on ver and as , light-trap catch ( beside an occupied untreated bednet ) , window exit-trap catch and pyrethrum spray collection s. During the first year of intervention ( June 1992 to July 1993 ) the treated bednets provided personal protection for people sleeping under them , but had very little impact on densities of An.gambiae collected on human bait . The human blood index ( HBI ) of An.gambiae was not affected ( HBI = 99 % in villages with and without nets ) . An.gambiae parous rates were significantly reduced in all intervention villages , but malaria sporozoite rates fell in only some of the villages . These results are intermediate between those obtained from other projects in Tanzania and Burkina Faso , where treated bednets reduced man-biting , parity and sporozoite rates , versus The Gambia where treated bednets had no significant impact on any of these factors . Possible reasons for these contrasted findings are discussed Information on the impact of insecticide (permethrin)-treated bed nets ( ITNs ) from r and omized controlled trials in areas of intense perennial malaria transmission is limited . As part of a large-scale , community-based , group-r and omized controlled trial of the effect of ITNs on childhood mortality in a holoendemic area in western Kenya , we conducted three cross-sectional surveys in 60 villages to assess the impact of ITNs on morbidity in 1,890 children less than three years old . Children in ITN and control villages were comparable pre-intervention , but after the introduction of ITNs , children in intervention villages were less likely to have recently experienced illness requiring treatment ( protective efficacy [ 95 % confidence intervals ] = 15 % [ 1 - 26 % ] ) , have an enlarged spleen ( 32 % [ 20 - 43 % ] ) , be parasitemic ( 19 % [ 11 - 27 % ] ) , have clinical malaria ( 44 % [ 6 - 66 % ] ) , have moderately severe anemia ( hemoglobin level < 7.0 g/dL ; 39 % [ 18 - 54 % ] ) , or have a pruritic body rash , presumably from reduced nuisance insect bites ( 38 % [ 24 - 50 % ] ) . Use of ITNs was also associated with significantly higher mean weight-for-age Z-scores and mid-upper arm circumferences . There was no evidence , however , that ITNs reduced the risk of helminth infections , diarrhea , or upper or lower respiratory tract infections . The ITNs substantially reduced malaria-associated morbidity and improved weight gain in young children in this area of intense perennial malaria transmission Two case-control studies , one on mortality and the other on malaria morbidity , were carried out in order to evaluate the impact of the Gambian National Insecticide Bed Net Programme during the second year of intervention and to explore the feasibility of such a study for the evaluation of programme effectiveness . For the mortality study , children 1 - 9 years old who died during the 1993 rainy season were matched by age and sex with 2 healthy controls from the same village . For the morbidity study , children 1 - 9 years old attending Fatoto or Jahalia Health Centres in The Gambia and who had fever and parasitaemia > or = 5000/microL were matched by age with a child attending the health centres without fever or parasitaemia . An additional healthy control was recruited from the case 's village . No impact of insecticide-treated bed nets on mortality was detected and this was in keeping with the results obtained by prospect i ve surveillance . A protective effect of insecticide-treated nets on malaria morbidity was detected when cases were compared with controls recruited at the health centres . However , this disappeared when cases were compared with controls recruited from the cases ' villages . The mortality case-control study suggested that reducing the time between onset of disease and treatment may have an important impact on childhood mortality . In order to calculate programme cost-effectiveness , important for informed re source allocations to be made by health managers , it is essential to obtain evidence of effectiveness . This can be done by means of case-control studies , which are easier to carry out and require fewer re sources than prospect i ve surveillance . Nevertheless , it is necessary to be conscious of their pitfalls , particularly of the bias involved in the choice of cases and controls . The measurement of insecticide on the nets of the cases or controls is essential for such studies BACKGROUND About 90 percent of the deaths from malaria are in African children , but criteria to guide the recognition and management of severe malaria have not been vali date d in them . METHODS We conducted a prospect i ve study of all children admitted to the pediatric ward of a Kenyan district hospital with a primary diagnosis of malaria . We calculated the frequency and mortality rate for each of the clinical and laboratory criteria in the current World Health Organization ( WHO ) definition of severe malaria , and then used logistic-regression analysis to identify the variables with the greatest prognostic value . RESULTS We studied 1844 children ( mean age , 26.4 months ) with a primary diagnosis of malaria . Not included were 18 children who died on arrival and 4 who died of other causes . The mortality rate was 3.5 percent ( 95 percent confidence interval , 2.7 to 4.3 percent ) , and 84 percent of the deaths occurred within 24 hours of admission . Logistic-regression analysis identified four key prognostic indicators : impaired consciousness ( relative risk , 3.3 ; 95 percent confidence interval , 1.6 to 7.0 ) , respiratory distress ( relative risk , 3.9 ; 95 percent confidence interval , 2.0 to 7.7 ) , hypoglycemia ( relative risk , 3.3 ; 95 percent confidence interval , 1.6 to 6.7 ) , and jaundice ( relative risk , 2.6 ; 95 percent confidence interval , 1.1 to 6.3 ) . Of the 64 children who died , 54 were among those with impaired consciousness ( n = 336 ; case fatality rate , 11.9 percent ) or respiratory distress ( n = 251 ; case fatality rate , 13.9 percent ) , or both . Hence , this simple bedside index identified 84.4 percent of the fatal cases , as compared with the 79.7 percent identified by the current WHO criteria . CONCLUSIONS In African children with malaria , the presence of impaired consciousness or respiratory distress can identify those at high risk for death Between 1991 and 1994 , an intervention program with permethrin- and lambdacyhalothrin-impregnated bed nets was carried out over a period of nine months in each of five endemic , malarious areas of Ecuador , Peru , and Colombia . This program was evaluated through household surveys , blood sampling , in-depth longitudinal studies , and entomologic analysis . Eighty-four communities ( including approximately 35,000 individuals ) were paired according to malaria incidence , size , and coverage with bed nets and then r and omly allocated to intervention and control groups . The results showed that peoples ' acceptance of the measure was related to their perception of an immediate protective effect against insects . The effectiveness of the bed nets , measured as a reduction of malaria incidence in intervention communities as against control communities , showed large variations between and within the study areas . The protective efficacy varied between 0 % and 70 % when looking only at the postintervention differences between intervention and control groups . The average protection was 40.8 % when considering a four-month incidence of clinical malaria attacks and 28.3 % when considering a two-week malaria incidence . Important factors for the success of the bed net program were insect susceptibility to pyrethroids , high coverage with impregnated bed nets , high malaria incidence , good community participation , high mosquito densities when people go to bed , and a high proportion of Plasmodium falciparum . In one area , where DDT spraying in the control communities was executed , the effectiveness of bed net impregnation was slightly better than that of spraying A r and omized controlled trial of insecticide-treated bed nets ( ITNs ) was conducted in an area of high malaria transmission in Tanzania in order to assess the effects of ITNs on infection and anaemia . One hundred and twenty-two children , aged 5 to 24 months , were r and omly allocated to 2 groups , one of which received ITNs . Outcome measures were assessed in 6 consecutive months with monthly cross-sectional surveys . These measures were haemoglobin values , Plasmodium falciparum prevalence and density , and multiplicity of infection determined by polymerase chain reaction-restriction fragment length polymorphism analysis ( PCR-RFLP ) of the msp2 locus . There was a significant increase in mean heamoglobin values and a significant decrease of 16.4 % in microscopically determined P. falciparum prevalence in children in the ITN group six months after the start of the trial . Both effects were more pronounced in younger children . However , no significant difference was observed in parasite density or multiplicity of infection among infected children . Comparison with PCR results indicated that microscopically subpatent parasitaemia was more frequently found in children in the ITN group . This , together with the observed similar multiplicity in the 2 groups , suggests that infections are maintained despite ITN use , owing to the chronicity of infections . This study shows that ITNs reduce the risk of anaemia in highly exposed young children . The virtually unchanged multiplicity of infection indicates that the potentially protective concomitant immunity is not compromised A r and omized , double-blind , field trial was carried out to compare the effectiveness of permethrin-treated bed nets with that of untreated nets as a method of malaria control for migrant workers in eastern Thail and . The study was conducted using 261 subjects in eastern rural areas that are known to be highly endemic for multidrug-resistant Plasmodium falciparum infection . One hundred twenty-six subjects used treated nets , while 135 used untreated nets . During the 35 weeks of observation , 23 subjects using treated nets and 33 workers using untreated nets developed 28 and 51 episodes of malaria , respectively ( P = 0.029 ) . The reduction in risk per subject due to treated nets was 0.06 . The residual effects of permethrin were tested using a World Health Organization st and ard bioassay . Anti-mosquito activity was found to be present in the nets for more than 16 months . We conclude that because of the failure of the development of safe , effective , long-lasting prophylactic agents , integrating the use of impregnated nets with large-scale primary health care programs may be a partially effective method for controlling malaria in eastern Thail and The verbal autopsy ( VA ) is an epidemiological tool that is widely used to ascribe causes of death by interviewing bereaved relatives of children who were not under medical supervision at the time of death . This technique was assessed by comparison with a prospect i ve survey of 303 childhood deaths at a district hospital in Kenya where medically confirmed diagnoses were available . Common causes of death were detected by VA with specificities greater than 80 % . Sensitivity of the VA technique was greater than 75 % for measles , neonatal tetanus , malnutrition , and trauma-related deaths ; however , malaria , anaemia , acute respiratory-tract infection , gastroenteritis , and meningitis were detected with sensitivities of less than 50 % . There may have been unwarranted optimism in the ability of VAs to detect some of the major causes of death , such as malaria , in African children . VA used in malaria-specific intervention trials should be interpreted with caution and only in the light of known sensitivities and specificities The effects of introducing permethrin-impregnated bednets on local population s of the malaria vector mosquitoes Anopheles funestus and the An.gambiae complex was monitored during a r and omized controlled trial at Kilifi on the Kenyan coast . Pyrethrum spray collection s : inside 762 households were conducted between May 1994 and April 1995 after the introduction of bednets in half of the study area . All-night human bait collection s were performed in two zones ( one control and one intervention ) for two nights each month during the same period . PCR identification s of An.gambiae sensu lato showed that proportions of sibling species were An.gambiae sensu stricto > An.merus > An.arabiensis . Indoor-resting densities of An.gambiae s.l . and the proportion of engorged females decreased significantly in intervention zones as compared to control zones . However , the human blood index and Plasmodium falciparum sporozoite rate remained unaffected . Also vector parous rates were unaltered by the intervention , implying that survival rates of malaria vectors were not affected . The human-biting density of An.gambiae s.l . , the predominant vector , was consistently higher in the intervention zone compared to the control zone , but showed 8 % reduction compared to pre-intervention biting rates-versus 94 % increase in the control zone . Bioassay , susceptibility and high-performance liquid chromatography results all indicated that the permethrin content applied to the nets was sufficient to maintain high mortality of susceptible vectors throughout the trial . Increased rates of early outdoor-biting , as opposed to indoor-biting later during the night , were behavioural or vector composition changes associated with this intervention , which would require further monitoring during control programmes employing insecticide-treated bednets In an intensely malarious area in north-east Tanzania , microencapsulated lambdacyhalothrin was used in four villages for treatment of bednets ( provided free of charge ) and in another four villages the same insecticide was used for house spraying . Another four villages received neither intervention until the end of the trial but were monitored as controls . Bioassays showed prolonged persistence of the insecticidal residues . Light traps and ELISA testing showed reduction of the malaria vector population s and the sporozoite rates , leading to a reduction of about 90 % in the entomological inoculation rate as a result of each treatment . Collection s of blood fed mosquitoes showed no diversion from biting humans to biting animals . Incidence of re-infection was measured by weekly monitoring of cohorts of 60 children per village , after clearing preexisting infection with chlorproguanil-dapsone . The vector control was associated with a reduction in probability of re-infection per child per week by 54 - 62 % , with no significant difference between the two vector control methods . Cross-sectional surveys for fever , parasitaemia , haemoglobin and weight showed association of high parasitaemia with fever and anaemia and beneficial effects of each intervention in reducing anaemia . However , passive surveillance by resident health assistants showed no evidence for reduced prevalence of fever or parasitaemia . Net treatment consumed only about one sixth as much insecticide as house spraying and it was concluded that the former intervention would work out cheaper and nets were actively dem and ed by the villagers , whereas spraying was only passively assented to This paper describes planning , implementation , monitoring and evaluation activities carried out in support of a malaria control project that used permethrin-impregnated curtains in eight villages in rural Malawi . Findings from formative evaluation and project monitoring aspects of the evaluation are presented . Permethrin-impregnated curtains were introduced to villagers who participated in household self-help projects . To implement the project , village health workers were trained and worked closely with existing project personnel as well as traditional headmen to assure village participation , facilitate health education and coordinate curtain-dipping ( impregnation ) meetings . A quasi-experimental evaluation design used surveys and observations to measure change in cognitive , behavioural and health outcome indicators . Village adoption rates averaged 50 % , with variation between villages . Monitoring data showed a high degree of compliance with curtain re-impregnation initially and high perceived efficacy of curtains . Issues discussed include village readiness for change , trust , acceptability of the innovation , cost , sustainability and leadership BACKGROUND Lately , the number of systematic review s published has increased substantially . Many systematic review s exclude trials published in language s other than English . However , there is little empirical evidence to support this action . We looked for differences in the completeness of reporting between trials published in other language s and those published in English , to see whether the exclusion of trials published in other language s is justified . METHODS We compared completeness of reporting , design characteristics , and analytical approaches of 133 r and omised controlled trials ( RCTs ) published in English between 1989 and 1994 and 96 published in French , German , Italian , or Spanish during the same time . RCTs were identified by h and search ing of journals ( seven in English and six in the other language s ) . FINDINGS We found no significant differences between trials published in English and other- language trials for any single item in the completeness of reporting scale ( r and omisation , double-blinding , withdrawals ) , or for the overall score ( percentage of maximum possible score 51.0 % for trials in English , 46.2 % for trials in other language s ; 95 % CI for difference -1.1 to 10.5 ) . Other- language trials were more likely than English- language trials to have adult participants , to use two or more interventions , and to compare two or more active treatments without an untreated control group . Trials in other language s were less likely to report a clearly prespecified primary outcome or any rationale for sample size estimation . INTERPRETATION These results provide evidence for inclusion of all trial reports , irrespective of the language in which they are published , in systematic review s. Their inclusion is likely to increase precision and may reduce systematic errors . We hope that our findings will prove useful to those developing guidelines and policies for the conduct of reporting of systematic review A community-based r and omized , controlled trial of permethrin impregnated bednets was carried out in a rural area of northern Ghana , between July 1993 and June 1995 , to assess the impact on the mortality of young children in an area of intense transmission of malaria and no tradition of bednet use . The district around Navrongo was divided into 96 geographical areas and in 48 r and omly selected areas households were provided with permethrin impregnated bednets which were re-impregnated every 6 months . A longitudinal demographic surveillance system was used to record births , deaths and migrations , to evaluate compliance and to measure child mortality . The use of permethrin impregnated bednets was associated with 17 % reduction in all-cause mortality in children aged 6 months to 4 years ( RR = 0.83 ; 95 % CI 0.69 - 1.00 ; P = 0.05 ) . The reduction in mortality was confined to children aged 2 years of younger , and was greater in July-December , during the wet season and immediately after ( RR = 0.79 ; 95 % CI 0.63 - 1.00 ) , a period when malaria mortality is likely to be increased , than in the dry season ( RR = 0.92 , 95 % CI 0.73 - 1.14 ) . The ready acceptance of bednets , the high level of compliance in their use and the subsequent impact on all-cause mortality in this study has important implication s for programmes to control malaria in sub-Saharan Africa A trial was undertaken in a rural area of The Gambia to investigate the impact of permethrin-treated bed nets on malaria . Two groups of children , matched for age , sex , and malaria exposure , were followed through the rainy season of 1985 for illness and febrile episodes . One group of 205 children slept under permethrin-treated bed nets ( 0.5 g/m2 ) ; 184 children who slept under placebo-treated nets formed the control group . At the end of the rains the children were examined for splenomegaly and blood sample s were taken for determination of packed cell volume ( PCV ) and parasitaemia . Permethrin treatment of bed nets was well accepted and was without side-effects . Children who slept under treated nets had significantly fewer episodes of clinical malaria than control children . However , at the end of the rains there was no significant difference in the prevalence of splenomegaly or parasitaemia or in the mean PCV between the groups . It is suggested that permethrin treatment of nets may have a greater effect on the duration of probing by mosquitoes for a blood meal than on the number of bites received A r and omized controlled trial investigated the impact of community-wide use of mosquito nets impregnated with lambda-cyhalothrin alone or with dapsone/pyrimethamine ( d/p ) prophylaxis on clinical malaria due to perennially transmitted Plasmodium falciparum in children in the Bo district of Sierra Leone . The 17 study communities were pair-matched and r and omly allocated to receive treated mosquito nets or no nets and the children ( age range = 3 months-6 years ) in each community were r and omly allocated to receive d/p or placebo individually every two weeks . This result ed in each of the approximately 2,000 children recruited being in one of four study groups ( impregnated mosquito nets and d/p prophylaxis , impregnated mosquito nets , d/p prophylaxis , and controls ) . The intervention phase of the study lasted 12 months . A total of 1,800 children attended more than 25 % of the 48 total weekly morbidity surveillance surveys and were included in the analysis . The effects of the exclusive use of either treated mosquito nets or d/p prophylaxis on protection against clinical malaria due to P. falciparum was significantly similar ( 49 % and 42 % , respectively ) , while in combination this protective efficacy was significantly increased to 72 % ( 95 % confidence interval = 67 - 76 % ) . Children in the control group had an average of 1.3 clinical malaria episodes per child annually compared with 0.65 episodes or 0.78 episodes for those using treated mosquito nets and d/p , respectively . Children using both treated mosquito nets and d/p prophylaxis had an average of 0.37 episodes per child . The interventions significantly reduced spleen rates and increased hematocrit values , and reduced the duration of episodes of clinical malaria BACKGROUND Some r and omised controlled trials ( RCTs ) done in German-speaking Europe are published in international English- language journals and others in national German- language journals . We assessed whether authors are more likely to report trials with statistically significant results in English than in German . METHODS We studied pairs of RCT reports , matched for first author and time of publication , with one report published in German and the other in English . Pairs were identified from reports round in a manual search of five leading German- language journals and from reports published by the same authors in English found on Medline . Quality of methods and reporting were assessed with two different scales by two investigators who were unaware of authors ' identities , affiliations , and other characteristics of trial reports . Main study endpoints were selected by two investigators who were unaware of trial results . Our main outcome was the number of pairs of studies in which the levels of significance ( shown by p values ) were discordant . FINDINGS 62 eligible pairs of reports were identified but 19 ( 31 % ) were excluded because they were duplicate publications . A further three pairs ( 5 % ) were excluded because no p values were given . The remaining 40 pairs were analysed . Design characteristics and quality features were similar for reports in both language s. Only 35 % of German- language articles , compared with 62 % of English- language articles , reported significant ( p < 0.05 ) differences in the main endpoint between study and control groups ( p = 0.002 by McNemar 's test ) . Logistic regression showed that the only characteristic that predicted publication in an English- language journal was a significant result . The odds ratio for publication of trials with significant results in English was 3.75 ( 95 % CI 1.25 - 11.3 ) . INTERPRETATION Authors were more likely to publish RCTs in an English- language journal if the results were statistically significant . English language bias may , therefore , be introduced in review s and meta-analyses if they include only trials reported in English . The effort of the Cochrane Collaboration to identify as many controlled trials as possible , through the manual search of many medical journals published in different language s will help to reduce such bias The impact of insecticide-treated bednet use on malaria and anaemia in pregnancy was assessed , as a supplementary study , in a major WHO/TDR-supported bednet trial in northern Ghana between July 1994 and April 1995 . The study area was divided into 96 clusters of compounds , with 48 clusters being r and omly allocated to intervention . All pregnant women were included in the study but the focus was on primigravidae and secundigravidae . 1961 pregnant women were recruited into the study --1033 ( 52.7 % ) in the treated bednet group and 928 ( 47.3 % ) in the no net group . 1806 ( 92.1 % ) had blood taken for malaria microscopy and haemoglobin determination in the third trimester . Pregnancy outcomes were reported for 847 women . The characteristics of women in intervention and control groups were comparable . The odds ratios , with 95 % confidence interval ( CI ) , for different study endpoints were , for Plasmodium falciparum parasitaemia--0.89 ( 0.73 , 1.08 ) , for anaemia--0.88 ( 0.70 , 1.09 ) , for low birthweight (LBW)--0.87 ( 0.63 , 1.19 ) , indicating no benefit for treated bednet use . Effective net use by parity varied from 42 % in primigravidae to 63 % in multigravidae , in spite of free nets and insecticide impregnation . The main reasons for not using a net were warm weather and perceived absence of mosquito biting . Chloroquine use in pregnancy was low and comparable in both groups . Implication s of findings for malaria control in pregnancy and further research are discussed Field trials in tropical medicine are often design ed so that intact social units ( e.g. , families , schools , communities ) rather than independent individuals are r and omized to an intervention group . Reasons are diverse , but include administrative convenience , a desire to reduce the effect of treatment contamination , and the need to avoid ethical issues that might otherwise arise . Dependencies among cluster members typical of such design s must be considered when determining sample size and analysing the result ing data . Failure to do so can result in false conclusions that the treatment is effective . The purpose of this paper is to compare different methods which can be used to construct tests of the effect of treatment when outcomes are binary ( e.g. , infected/uninfected ) . The discussion will be illustrated using data from a trial which r and omly assigned families to either a control group or a screening and treatment programme for imported intestinal parasites A malaria intervention trial was conducted for two years to evaluate the efficacy of permethrin-impregnated bed nets in reducing malaria infection and splenomegaly in two different age groups , ie below and over age of ten , in a hyperendemic area in Irian Jaya , Indonesia . Permethrin-impregnated or placebo-treated bed nets were provided to a treated and a control village , respectively . Immediately after periods with moderate rainfall in the first year , treated bed nets decreased P. falciparum and P. vivax density in the blood of children < 10 years ( group 1 ) but did not reduce the percentage of infection with either species . Children > 10 and adults ( group 2 ) showed significant reduction only in P. falciparum infection rates and density , whereas P. vivax was not influenced . After an excessive rainfall season in the second year , the risk for P. falciparum infections in both age groups using treated nets was less than half of that in the control village . P. vivax infection rates were significantly lower in the treated village at the beginning of and after these heavy rainfalls . In the treated village , spleen enlargement was markedly reduced in the younger age group during the second year In villages of northern Guadalcanal in the Solomon Isl and s , where the predominant malaria vector is An.farauti No. 1 and An.puctulatus is also involved , malaria transmission rates were compared for three zones : ( 1 ) non-intervention : 438 people in seventeen villages ; ( 2 ) residual DDT house-spraying two cycles per year : 644 people in thirty villages ; ( 3 ) bednets impregnated with permethrin 0.5 g/m2 twice per year , used by 580 people in sixteen villages . Regular DDT spraying in zones 1 and 3 had been withdrawn 18 months previously . Malariological blood smear surveys of children aged 1 - 9 years in August 1986 to January 1987 showed a mean baseline malaria parasite rate of 38 % ( 32/84 ) . By February 1988 , 18 months after introduction of impregnated bednets , the Plasmodium falciparum infection rate in children was lowest in the zone using impregnated bednets ( 21 % of 29 ) , intermediate in the untreated zone ( 29 % of 34 ) and highest in the DDT zone ( 46 % of 53 ) , but these differences were not statistically significant . P. vivax infection rates were 9 - 14 % . Using ELISA tests for malaria circumsporozoite antigen in the vectors , overall positivity rates were 0.7 % of 49,902 An.farauti and 2.54 % of 118 An.punctulatus , comprising 228 P.falciparum and 124 P.vivax infections . In the study zones , vector positivity rates were 0.93 % of 31,615 An.farauti in the untreated zone ; 0.32 % of 16,883 An.farauti in the DDT zone ; 0.07 % of 1404 An.farauti and 2.54 % of 118 An.puctulatus in the impregnated bednet zone . here was no significant correlation between malaria parasite rates in the vectors and the children . ( ABSTRACT TRUNCATED AT 250 WORDS Methods of confidence interval construction are provided for summary measures of treatment effect arising from design s r and omizing clusters to one of two treatment groups . Three basic design s are considered for the case of continuous and dichotomous variables : completely r and omized , pair-matched and stratified |
12,939 | 15,505,149 | Conclusion : Evidence on the efficacy of oral antispastic drugs in NPND is weak and does not include evaluation of patients ’ quality of life .
If any , efficacy is marginal .
Adverse drug reactions were common . | Objective : To assess the efficacy of oral drugs in the treatment of spasticity in patients with nonprogressive neurologic disease ( NPND ) . | A study was performed to evaluate the extent to which the medical literature may be misleading as a result of selective publication of r and omized clinical trials ( RCTs ) with results showing a statistically significant treatment effect . Three hundred eighteen authors of published trials were asked whether they had participated in any unpublished RCTs . The 156 respondents reported 271 unpublished and 1041 published trials . Of the 178 completed unpublished RCTs with a trend specified , 26 ( 14 % ) favored the new therapy compared to 423 of 767 ( 55 % ) published reports ( p less than 0.001 ) . For trials that were completed but not published , the major reasons for nonpublication were " negative " results and lack of interest . From the data provided , it appears that nonpublication was primarily a result of failure to write up and su bmi t the trial results rather than rejection of su bmi tted manuscripts . The results of this study imply the existence of a publication bias of importance both to meta- analysis and the interpretation of statistically significant positive trials A double-blind study was carried out in 30 patients suffering from spasticity due to cerebrovascular lesions to compare the long-term efficacy and tolerability of tizanidine hydrochloride with that of baclofen . A 2-week titration phase identified the optimum dose of tizanidine ( max . 20 mg/day ) or baclofen ( max . 50 mg/day ) in each patient . Patients were then treated with this dose for a 50-week maintenance phase . Efficacy and tolerability parameters were evaluated first on a monthly and then on a bimonthly basis . Both tizanidine and baclofen caused an improvement in the symptoms associated with spasticity . In end-point analysis , 87 % of patients showed an improvement ( p less than 0.01 ) in excessive muscle tone - the major efficacy parameter in this study - in the tizanidine group , while 79 % improved ( p less than 0.01 ) in the baclofen group . Side-effects in the tizanidine group were mild and transient and no patients discontinued the study ; in the baclofen group , 3 patients discontinued the study due to severe side-effects . However , both drugs were assessed as effective and fairly well tolerated in the long-term . Although there were no statistically significant differences between the two drugs , the global assessment of antispastic efficacy revealed a nearly significant difference ( p = 0.057 ) in favour of tizanidine and the global assessment of tolerability was also in favour of tizanidine A study was carried out to determine the efficacy and long-term safety of dantrolene in treating stroke patients with spasticity limiting rehabilitation . Fifteen of the 18 patients studied experienced reduction in spasticity and clinical improvement after treatment with dantrolene sodium for 6 weeks . Fourteen of these patients participated in a 6-week , double-blind , placebo-controlled study . The 5 patients who continued to receive dantrolene did not experience clinical deterioration . However , the 9 patients given placebo noted increased deficits . Seven asked that the blind be broken and chose to resume dantrolene therapy . After 6 weeks , 13 of the 14 patients elected to continue on dantrolene ( average dose 165.4 mg/day ) . All continued to improve . Side-effects were generally mild and transient . Although these patients took other drugs concomitantly , no drug interactions were reported A double-blind , placebo-controlled trial was conducted to determine whether early exhibition of Dantrium ( Dantrolene Sodium ) in patients with cerebrovascular accidents , before the onset of significant spasticity , would enhance the functional outcome of rehabilitation . Thirty-eight patients were enrolled in the trial and 31 satisfactorily completed the study . A modified Cybex isokinetic dynamometer was used to gather information on strength and muscle tone . Clinical , functional , and biochemical data were also collected . It was found that Dantrium reduced strength in the unaffected limbs but did not alter strength in the paretic limbs . Dantrium produced no alteration in clinical tone , functional outcome , or biochemical tests at the dosage ( 200 mg per day ) used in this study A double-blind study was carried out in 105 patients with chronic spasticity associated with hemiplegia in order to compare the efficacy and tolerability of tizanidine with that of diazepam . Dosage was increased progressively , if tolerated , to a maximum of 24 mg tizanidine or 30 mg diazepam per day at the end of 2 weeks . The optimum dosage was then maintained for 6 weeks . Efficacy and tolerability parameters were assessed after 2 and 8-weeks ' therapy . Patients on tizanidine but not those on diazepam showed a statistically significant improvement in functional status , as assessed by walking distance on flat ground . Analysis of the stretch reflex in four groups of muscles showed that both tizanidine and diazepam reduced the duration of contractions and increased the angle at which contraction occurred , but there were no significant differences between the two drugs . Clonus of the triceps surae resolved in 48 % of tizanidine and 40 % of diazepam patients . Evaluation of the effect of therapy revealed an improvement with each drug in approximately 83 % of patients , with the overall evaluation being slightly ( but non-significantly ) in favour of tizanidine . There were fewer discontinuations of treatment in the tizanidine group as a result of side-effects . It would appear , therefore , that tizanidine is an effective and well-tolerated drug in the treatment of cerebral spasticity Our serendipitous observations suggested that some patients with spasticity appeared to have improved following the administration of the anticonvulsant drug gabapentin . As some patients with spasticity are either refractory to or intolerant of established medical treatments , we conducted this study to investigate the effect of gabapentin on spasticity in patients with spinal cord injury . Twenty-five patients with spinal cord injury and spasticity received oral gabapentin ( 2400 mg over 48 h ) in a r and omized , double blind , placebo-controlled crossover study . We assessed responses by measuring the Ashworth spasticity scale , muscle stretch reflexes , presence of clonus and reflex response to noxious stimuli . Patient ratings were obtained using a Likert Scale . Administration of gabapentin , but not placebo , was associated with an 11 % reduction in spasticity as measured by the Ashworth Scale ( P=0.04 ) and by a 20 % reduction in the Likert Scale ( P=0.0013 ) . Significant changes were not obtained for the other measures . The data obtained suggest that gabapentin may be useful in the management of spasticity associated with spinal cord injury OBJECTIVE To determine if orally delivered tizanidine will control spastic hypertonia due to acquired brain injury . DESIGN R and omized , double-blind , placebo-controlled , crossover design , with 2 8-week treatment arms separated by a 1-week washout period at baseline . Patients were r and omly assigned to receive tizanidine or a matching placebo . SETTING Tertiary care outpatient and inpatient rehabilitation center attached to a university hospital . PARTICIPANTS Seventeen persons recruited in a consecutive manner , 9 of whom had suffered a stroke and 8 a traumatic brain injury , and had more than 6 months of intractable spastic hypertonia . INTERVENTION Over a 6-week period , subjects were slowly titrated up to their maximum tolerated dose ( up to 36 mg/d ) . Following a 1-week drug taper and 1-week period in which no study drug was administered , patients were then crossed over to the other study medication following an identical titration regime . MAIN OUTCOME MEASURES Subjects were evaluated for dose and effect throughout the trial as well as for side effects . Data for Ashworth rigidity scores , spasm scores , deep tendon reflex scores , and motor strength were collected on the affected upper extremity ( UE ) and lower extremity ( LE ) . Differences over time were assessed via descriptive statistics , Friedman 's analysis , and Wilcoxon 's signed-rank . Data are reported as the mean + /- 1 st and ard deviation . RESULTS Following 4 weeks of treatment when subjects reached their maximal tolerated dosage , the average LE Ashworth score on the affected side decreased from 2.3 + /- 1.4 to 1.7 + /- 1.1 ( p < .0001 ) . The spasm score decreased from 1.0 + /- 0.9 to 0.5 + /- 0.8 ( p = .0464 ) , while the reflex score was not statistically significant decreasing from 2.2 + /- 1.0 to 2.0 + /- 1.1 ( p = .0883 ) . The average UE Ashworth score on the affected side decreased from 1.9 + /- 1.1 to 1.5 + /- 0.9 ( p < .0001 ) . There was no significant change in the UE spasm and reflex scores . While there were positive placebo effects on motor tone , the active drug was still significantly better than placebo for decreasing LE tone ( p = .0006 ) and UE tone ( p = .0007 ) . With a reduction in motor tone , there was an increase in motor strength ( p = .0089 ) . The average dosage at 4 weeks was 25.2mg/d . CONCLUSION Tizanidine is effective in decreasing the spastic hypertonia associated with acquired brain injury , which is dose-dependent . There are limitations on its use due to side effects related to drowsiness A double-blind study was carried out on 20 children with spasticity secondary to cerebral palsy , in order to compare the effects of dantrolene sodium suspension and a placebo . The drug was found to be physiologically active in reducing the force of muscle contraction , but objective functional improvement , as measured by multiple performance tests , was irregular and probably not significant A double-blind crossover trial against placebo was conducted to assess the effects of the GABA derivative , baclofen , on the disabilities due to muscle spasticity in twenty children suffering from cerebral palsy . Baclofen performed very significantly better than placebo in reducing spasticity and significantly better than placebo in allowing both active and passive limb movements to be carried out . Notable improvement was also seen in scissoring . Side-effects were minimal and responded promptly to dose reduction . The evaluation of drug effects on muscle spasticity and the pharmacodynamics of baclofen are discussed . Recommendations are made regarding dosage of baclofen in childhood A double blind cross-over trial of Valium against Amytal and Placebo was carried out on 22 patients with spasticity due to spinal cord injuries . Observations were made by six independent observers . Valium was significantly more effective than Amytal or Placebo . There was a low incidence of side-effects |
12,940 | 30,016,540 | No adverse effects were reported with either the povidone-iodine or chlorhexidine vaginal cleansing .
AUTHORS ' CONCLUSIONS Vaginal preparation with povidone-iodine or chlorhexidine solution compared to saline or not cleansing immediately before cesarean delivery probably reduces the risk of post-cesarean endometritis .
Subgroup analysis could not rule out larger reductions in endometritis with antiseptics in women who were in labor or in women whose membranes had ruptured when antiseptics were used . | BACKGROUND Cesarean delivery is one of the most common surgical procedures performed by obstetricians .
Infectious morbidity after cesarean delivery can have a tremendous impact on the postpartum woman 's return to normal function and her ability to care for her baby .
Despite the widespread use of prophylactic antibiotics , postoperative infectious morbidity still complicates cesarean deliveries .
This is an up date of a Cochrane review first published in 2010 and subsequently up date d in 2012 , and twice in 2014 .
OBJECTIVES To determine if cleansing the vagina with an antiseptic solution before a cesarean delivery decreases the risk of maternal infectious morbidities , including endometritis and wound complications .
We also assessed the side effects of vaginal cleansing solutions to determine adverse events associated with the intervention . | Objective : The purpose of the present study was to determine whether the vaginal preparation with povidone – iodine prior to caesarean delivery decreased the incidence of postpartum endometritis . Methods : The present study was a prospect i ve r and omized controlled trial in which subjects received a vaginal preparation with povidone – iodine solution immediately prior to caesarean delivery or received no vaginal preparation . The primary outcome measure was the rate of postpartum endometritis . Results : A significant decrease in post-caesarean endometritis was noted in the group that received the povidone – iodine vaginal preparation ( n = 334 ) compared with the control group ( n = 336 ) [ 6.9 vs. 11.6 % ; RR = 1.69 ; 95 % CI = 1.03–2.76 ] . No statistically significant differences in the incidence of endometritis were noted between the experimental and control groups among women who were not in labor at the time of the caesarean delivery [ 9.2 vs. 8.6 % ; RR = 1.05 ; 95 % CI = 0.58–1.90 ] , and no differences were found between groups when women with ruptured membranes were excluded from the analysis [ 9.6 vs. 6.7 % ; RR = 1.39 ; 95 % CI = 0.78–2.47 ] . Conclusions : Vaginal preparation with povidone – iodine solution immediately prior to a caesarean delivery reduces the risk of post-operative endometritis . This preemptive measure was only found to be beneficial in women whose membranes had ruptured and those who were in labor prior to caesarean surgery Objectives : To determine the carriage rate of enterococcus in the lower genital tract of women having a cesarean delivery and to determine whether a single 2-g intraoperative dose of ampicillin eradicates enterococcus from the lower genital tract . Methods : Lower genital tract cultures were taken in 84 women who were in labor or had ruptured membranes and who were about to have an indicated cesarean delivery . The subjects were r and omized to receive either a single 2-g dose of ampicillin or a cephalosporin as prophylaxis . Cultures were repeated 24 hours postpartum . Results : Enterococcus was isolated preoperatively in 33 subjects ( 39.3 % ) and postoperatively in 36 ( 42.9 % ) . The enterococcus was eradicated in five of 17 women ( 29.5 % ) who received ampicillin . Conclusion : These results suggest that a single 2-g dose of ampicillin does not eradicate enterococcus from the lower genital tract . ( Obstet Gynecol 1993;81:115 - 7 Abstract Objective : To evaluate the efficacy of preoperative vaginal cleansing using chlorhexidine 0.25 % antiseptic wipes on rates of postcesarean section ( CS ) infectious morbidities ( endometritis , febrile morbidity and wound infection ) . Methods : This prospect i ve r and omized trial was conducted among 218 pregnant women scheduled for term elective CS . Patients were equally divided into two groups by simple r and omization . After spinal anesthesia and catheterization under aseptic technique , the study group had preoperative vaginal cleansing using chlorhexidine 0.25 % antiseptic wipes for about 1 min , while the control group did not . All cases received the prophylactic antibiotics and the usual abdominal scrub . All participants received the routine postoperative care without other interventions . Adverse postcesarean infectious morbidities such as endometritis , febrile morbidity and wound infection were observed at the time of hospital discharge and weekly for 6 weeks postpartum . Results : Both groups were matched regarding the baseline patients ’ characteristics ( age , gestational age , BMI , operative time and postoperative hospital stay ) . Overall , post-CS infectious morbidity were significantly reduced from 24.4 % in the control group to 8.8 % in the intervention group ; p value < 0.05 . Marked reduction was seen in the incidence of endometritis ( 13.2 % in the control group versus 2.9 % in the intervention group ; p value < 0.05 ) . However , fever and wound infection showed no significant difference between both groups . Conclusion : Cleansing the birth canal with chlorhexidine 0.25 % wipes prior to elective CS appears to be effective in reducing rates of post-CS infectious morbidity mainly endometritis Abstract Objective : To assess the effect of povidone iodine versus benzalkonium chloride , which were applied preoperatively for vaginal disinfection in caesarean sections , on postoperative factors . Methods : One hundred and twenty patients underwent elective caesarean section were divided into three groups using the simple r and omisation method : Group 1 ( povidone iodine , n : 41 ) ; Group 2 ( benzalkonium chloride , n : 39 ) ; Group 3 ( control group , n : 40 ) . Demographic data , duration of operation , amount of bleeding , postoperative pain , time to first flatulence and defaecation , haematological parameters on postoperative day 1 were compared between three groups . Pain evaluation was performed at 6th and 24th postoperative hour using Visual Analogue Scale . Results : No statistically significant differences were detected between the groups in demographic characteristics . There were no significant differences between the groups with respect to the duration of operation and hospital stay . The patients in the group who underwent povidone iodine vaginal cleansing had statistically significantly less postoperative pain as compared to control group . No difference was observed between the groups in haematological parameters other than C-reactive protein ( CRP ) ; however , CRP levels at 24th post-operative hour were significantly lower in Group 1 compared to the other groups . Conclusions : The preoperative vaginal cleansing with povidone iodine could reduce the postoperative pain , analgesic need and infection parameter The introduction of antibiotic prophylaxis for cesarean delivery has decreased the risk of postpartum endometritis and wound infection , but factors that contribute to prophylaxis failure are not understood . To determine factors that might contribute to postpartum infections following antibiotic prophylaxis , we cultured amniotic fluid , decidua , and chorioamniotic membrane specimens for anaerobic and facultative bacteria and for genital mycoplasmas at cesarean delivery . Women were assessed daily for the development of infections , and if endometritis developed , a protected endometrial culture was obtained . Postpartum endometritis developed in 16 and wound infection in four of 102 women . Infection rates were similar for women receiving cefotetan ( N=50 ) or cefoxitin ( N=52 ) for prophylaxis . The isolation of group B streptococcus { P<.001 ) or Enterococcus faecalis { P=.03 ) from the upper genital tract at delivery was significantly associated with postpartum endometritis . Antibiotic- resistant organisms ( other than enterococci ) were recovered uncommonly at delivery or with postpartum infections . Group B streptococcus was susceptible to the prophylactic agents used , suggesting that virulence factors other than antibiotic resistance are important for the development of postpartum endometritis . Group B streptococcus , E faecalis , and bacteria associated with bacterial vaginosis were recovered from the endometrium at the time of postpartum endometritis OBJECTIVE Our purpose was to determine whether chlorhexidine vaginal irrigation prevents maternal peripartal infection . STUDY DESIGN A double-blinded , placebo-controlled , r and omized trial was performed . Single 200 ml irrigations of either 0.2 % chlorhexidine solution or sterile water placebo were given in active labor or before planned cesarean delivery . The primary outcome measure was the combined rate of chorioamnionitis and endometritis ( which were mutually exclusive diagnoses ) . RESULTS A total of 1024 patients were enrolled : 508 in the chlorhexidine group and 516 in the placebo group . The two groups were generally well balanced on important clinical factors but differed ( p < 0.05 ) in rates of nulliparity ( chlorhexidine 42 % , placebo 52 % ) , intrauterine pressure catheter usage ( chlorhexidine 65 % , placebo 72 % ) , and presence of meconium ( chlorhexidine 17 % , placebo 22 % ) . There were no recognized adverse maternal or neonatal reactions to irrigation . Rates of infection ( chorioamnionitis + endometritis ) did not differ significantly between the groups , chlorhexidine 10 % versus placebo 13 % ( relative risk 0.8 , 95 % confidence interval 0.5 to 1.1 ) . Stratified and logistic regression analyses supported the primary univariate analysis . Neonatal outcomes , including sepsis rates of 0.4 % , were equivalent for the groups . CONCLUSION As used in this trial , chlorhexidine lacked efficacy in the prevention of maternal peripartal infection BACKGROUND We found cesarean section ( C-section ) surgical site infection ( SSI ) at our institution was significantly higher than the national benchmark . METHODS A retrospective cohort study was conducted under 4 phases from January 2008-December 2014 . The hospital infection control ( IC ) policies and a presurgical checklist were bundled and implemented . The study was conducted with 3,334 cesarean deliveries : phase A ( January 1 , 2008-January 31,2010 ) : 1,250 patients without intervention ( baseline SSI rate ) , phase B ( February 1 , 2010-July 31 , 2011 ) : 682 patients were intervened with IC policies , phase C ( August 1 , 2011-December 31 , 2012 ) : 591 patients with an SSI reduction bundle , and phase D ( January 1 , 2013-December 31 , 2014 ) : 811 patients were monitored for C-section SSI sustainability . Patients not following strict protocol s because of emergency C-section deliveries were excluded . The χ2 test , Fisher exact test , and st and ard Z test were used for statistical analyses . RESULTS C-section SSI rates were 6.2 % ( 77/1,250 ) in phase A , 3.7 % ( 25/682 ) in phase B , 1.7 % ( 10/591 ) in phase C , and 0.1 % ( 1/811 ) in phase D , respectively . By implementing the IC policies and bundle , the C-section SSI rate was reduced 40.3 % ( phase B vs phase A ) , 72.6 % ( phase C vs phase A ) , and 98.4 % ( phase D vs phase A ) . All statistics were significantly different . CONCLUSIONS We conclude that implementing a C-section SSI reduction bundle was associated with reduced C-section SSI rate down toward zero . A future prospect ively r and omized controlled trial is warranted OBJECTIVE The objective of the study was to determine whether vaginal preparation with povidone iodine before cesarean delivery decreased the risk of postoperative maternal morbidities . STUDY DESIGN The design of the study was a r and omized , controlled trial in women undergoing cesarean delivery with subjects assigned to have a preoperative vaginal cleansing with povidone iodine or to a st and ard care group ( no vaginal wash ) . The primary outcome was a composite of postoperative fever , endometritis , sepsis , readmission , wound infection , or complication . RESULTS There were 155 vaginal cleansing subjects and 145 control subjects . Overall , 9.0 % developed the composite outcome , with fewer women in the cleansing group ( 6.5 % ) compared with the control group ( 11.7 % ) , although the difference was not statistically significant ( relative risk , 0.55 ; 95 % confidence interval , 0.26 - 1.11 ; P = .11 ) . Length of surgery , being in labor , and having a dilated cervix were all associated with the composite morbidity outcome . CONCLUSION Vaginal cleansing with povidone iodine before cesarean delivery may decrease postoperative morbidities , although the reduction is not statistically significant OBJECTIVE To estimate the efficacy of preoperative administration of intravaginal metronidazole for the prevention of postcesarean endometritis . METHODS This double‐masked , placebo‐controlled r and omized trial included patients of at least 24 weeks ' gestation undergoing cesarean deliveries for various indications . Patients were r and omized to receive either 5 g of metronidazole gel intravaginally or matching placebo before the initiation of the cesarean . All patients underwent surgical cleansing of the abdomen , and most received prophylactic antibiotics after cord clamping . Patients with chorioamnionitis and /or suspected allergy to metronidazole were excluded . For a two‐sided α of 0.05 and β of 0.20 ( 80 % power ) , 120 subjects were required in each group . The main outcome variable was the incidence of postcesarean endometritis . Secondary outcome variables included presence of febrile morbidity , wound infection , days on antibiotics , and length of postpartum hospitalization . Neonatal outcomes included birth weight , Apgar scores less than 7 at 5 minutes , umbilical arterial pH less than 7.16 , admission and length of stay in the neonatal intensive care unit , and length of hospital stay . RESULTS Of 112 patients receiving metronidazole , eight ( 7 % ) developed postcesarean endometritis , compared with 19 of 112 ( 17 % ) of those receiving placebo gel ( relative risk 0.42 , 95 % confidence interval 0.19 , 0.92 ) . No significant differences were noted between treatment groups with respect to the other outcome variables . CONCLUSION The preoperative administration of 5 g of intravaginal metronidazole gel appears to reduce the incidence of postcesarean endometritis The aerobic and anaerobic cervical microflora was determined before operation and on day 4 after operation in groups of women undergoing a clinical trial of prophylaxis with three doses of cefoxitin , cefazolin , or placebo for infectious complications of nonelective cesarean section . Floral shifts occurred post partum , with return of Escherichia coli and Bacteroides fragilis and a decrease in C and ida colonization . No significant differences in flora existed preoperatively among patients receiving cefoxitin , cefazolin , or placebo , but by day 4 , both antibiotic groups had greater enterococcal colonization . This difference was more marked with cefoxitin than with cefazolin . No difference in E. coli or B. fragilis colonization was noted by day 4 in placebo and antibiotic groups . Resistance developing in isolates in the antibiotic groups was mainly a result of enterococcal colonization . Results of this study indicate that a three-dose cephalosporin prophylactic regimen result ed in a significant selection of resistant enterococcal colonization but there was no increase in nosocomial infection in the antibiotic groups compared to the placebo group . There did not appear to be significant differences in either species selection or antibiotic resistance of aerobic or anerobic microflora between the cefoxitin and cefazolin groups OBJECTIVE Our purpose was to determine whether a dilute solution of chlorhexidine used as a one-time vaginal wash intrapartum can reduce the incidence of intraamniotic infection or endometritis in laboring pregnant women . STUDY DESIGN Term pregnant women in labor were prospect ively r and omized to receive either 20 ml of 0.4 % chlorhexidine ( n = 481 ) or 20 ml of sterile water ( n = 466 ) placebo . All patients were monitored for risk factors associated with intraamniotic infection . Continuous variables were compared with the Mann-Whitney U test and discrete variables were compared with Fisher 's exact test . RESULTS No significant differences in infection were found between the chlorhexidine and placebo groups . During the study period 21 of 466 women ( 4.5 % ) had intraamniotic infection in the control group compared with 25 of 481 women ( 5.2 % ) receiving chlorhexidine ( p = 0.65 , 95 % confidence interval 0.82 to 1.41 ) . Nine women in the placebo group ( 1.9 % ) and 9 women in the chlorhexidine group ( 1.9 % ) had endometritis ( p = 1.0 , 95 % confidence interval 0.62 to 1.56 ) . CONCLUSIONS Our findings suggest that a one-time 0.4 % chlorhexidine vaginal wash does not decrease the incidence of infectious morbidity in parturients , compared with the use of sterile water Fifteen hundred patients were enrolled in a prospect i ve , r and omized study on the effect of antibiotic prophylaxis during cesarean section . Two hundred thirty-one patients developed postpartum endometritis , and the isolates obtained from the endometrium were tested for sensitivity to ampicillin , cefuroxime , ofloxacin , ciprofloxacin , and clindamycin . Minimum inhibitory concentrations of 50 % and 90 % of ampicillin , cefuroxime , and clindamycin were similar to previously reported values ; however , slight differences were noted in the activity of the two quinolones to common pelvic isolates . The minimum inhibitory concentrations of 90 % of ofloxacin and ciprofloxacin to 119 isolates of Enterococcus faecalis were 4.0 and 2.0 , to 17 isolates of Staphylococcus aureus 1.0 and 0.5 , to 39 isolates of Escherichia coli 0.5 and 1.0 , to 46 isolates of Bacteroides bivius 4.0 and 8.0 , to 57 isolates of Gardnerella vaginalis 1.0 and 2.0 , to 71 isolates of Staphylococcus epidermidis 0.5 and 0.5 , to 16 isolates of Proteus mirabilis 0.25 and 0.12 , and to 50 isolates of Lactobacillus species 32.0 and 8.0 micrograms/ml , respectively . In summary , the quinolones have activity comparable with a variety of other oral agents versus female pelvic pathogens , with the quinolones ofloxacin and ciprofloxacin having better activity against most of the gram-negative isolates . Anaerobic activities were comparable with the beta-lactams , but inferior to clindamycin and metronidazole as expected To assess the effect of broad-spectrum antibiotic therapy upon vaginal colonization , we collected vaginal specimens for culturing at the end of therapy from 50 patients treated for postcesarean section endometritis . Infected patients had participated in a double-blind therapy protocol and had received either clindamycin plus gentamicin or cefam and ole plus placebo . Repeat vaginal culturing was performed 6 weeks later . Similar vaginal specimens for culturing were collected from 25 control patients who also had undergone cesarean section but had not received antibiotics . Of 26 patients treated with cefam and ole , 16 ( 62 % ) developed vaginal colonization with isolates resistant to that drug ; of 24 patients treated with clindamycin-gentamicin , two ( 8 % ) developed isolates resistant to these agents ( p less than 0.001 ) . Among 25 control patients , there was only one isolate resistant to cefam and ole and none resistant to clindamycin-gentamicin . Compared to controls , more antibiotic-treated patients developed isolates resistant to cefam and ole ( p = 0.001 ) and to clindamycin-gentamicin ( p = 0.06 ) . Colonization did not persist , and there were no late infections in this population Objective To determine whether vaginal preparation with povidone iodine before cesarean decreased the incidence of postpartum infectious morbidity . Methods Participants were r and omly assigned to vaginal preparation with povidone iodine ( n = 247 ) or no preparation ( n = 251 ) . Postpartum infectious morbidity included fever , defined as temperature of 38C or greater after the day of surgery ; endometritis , defined as fever with abdominal or uterine tenderness and initiation of intravenous antibiotics ; and wound separation , defined as disruption of the abdominal incision that required wound care . We calculated overall rates of postpartum infectious morbidity , relative risks ( RR ) , and 95 % confidence intervals ( CI ) for the effect of vaginal preparation . As design ed and reported , the trial had at least 80 % power to detect a 10 % or greater absolute difference in rates of overall infectious morbidity , fever , and endometritis ( two-tailed , & agr ; = 0.05 ) . Results There was no difference between groups in maternal age , parity , race , education , prior cesarean , type of anesthesia , labor before current cesarean , number of vaginal examinations during labor , internal monitoring , prophylactic antibiotic use , gestational age at delivery , or payment status . Excluding 68 women with chorioamnionitis , incidence of postoperative fever was 19.3 % , endometritis 7.2 % , and wound separation 7.0 % . Vaginal preparation with povidone iodine before cesarean had no effect on risk for fever ( RR 1.1 , 95 % CI 0.8 , 1.6 ) , endometritis ( RR 1.6 , 95 % CI 0.8 , 3.1 ) , or wound separation ( RR 0.6 , 95 % CI 0.3 , 1.3 ) . Conclusion Vaginal preparation with povidone iodine before cesarean had no effect on the incidence of fever , endometritis , or wound infection Three methods of vaginal preparation carried out before abdominal hysterectomy are compared . The lowest post-operative morbidity was associated with the use of a povidone-iodine douche and gel during the pre-operative preparation of the patient OBJECTIVE : Postcesarean endometritis and wound infection remain significant morbidities , despite use of strategies to prevent these complications . We investigated the effect of preoperative vaginal preparation with povidone-iodine as a preventive intervention against postcesarean endometritis and wound infection . METHODS : A r and omized controlled study was performed in 308 women undergoing nonemergent cesarean delivery . Subjects received either st and ard abdominal scrub alone or abdominal scrub with an additional vaginal preparation with povidone-iodine solution . All subjects received prophylactic antibiotic at the time of umbilical cord clamping . Each subject 's postoperative course was review ed for development of febrile morbidity ( temperature > 38.0 ° C ) , endometritis ( temperature > 38.4 ° C accompanied by fundal tenderness occurring beyond the first postoperative day , in the absence of evidence of other infection ) , and wound infection . RESULTS : Postcesarean endometritis occurred in 7.0 % of subjects who received a preoperative vaginal preparation and 14.5 % of controls ( P < .05 ) . There was no measurable effect of a vaginal scrub on the development of postoperative fever or wound infection . The adjusted odds ratio for developing endometritis after a vaginal preparation was 0.44 ( 95 % confidence interval [ CI ] 0.193–0.997 ) . Multivariate analysis showed an increased risk of developing endometritis in association with severe anemia ( adjusted OR 4.26 , 95 % CI 1.568–11.582 ) , use of intrapartum internal monitors ( adjusted OR 2.84 , 95 % CI 1.311–6.136 ) , or history of antenatal genitourinary infection ( adjusted OR 2.9 , 95 % CI 1.265–6.596 ) . CONCLUSION : Preoperative vaginal scrub with povidone-iodine decreases the incidence of postcesarean endometritis . This intervention does not seem to decrease the overall risk of postoperative fever or wound infection . LEVEL OF EVIDENCE : Background Worldwide caesarean section ( CS ) delivery is the most common major operation . Approximately 25 % of pregnant women undergo a CS in the UK for delivery of their babies . Sepsis and post-natal infection constitute significant maternal mortality and morbidity . Infection following a CS has a number of primary sources including endometritis occurring in 7–17 % of women . Sepsis reduction and reduction in antibiotic use have been identified as a national and international priority . The overarching aim of this research is to reduce infectious morbidity from caesarean sections . Methods This is a parallel group feasibility r and omised controlled trial comparing vaginal cleansing using chlorhexidine gluconate versus no cleansing ( st and ard practice ) at CS to reduce infection . Women will be recruited from four National Health Service maternity units . Two hundred fifty women ( 125 in each arm ) undergoing elective or emergency CS , who are aged 16 years and above , and at least 34 weeks pregnant will be r and omised . Allocation to treatment will be on a 1:1 ratio . The study includes a qualitative aspect to develop women centred outcomes of wellbeing after delivery . Discussion The success of the feasibility study will be assessed by criteria related to the feasibility measurements to ascertain if a larger study is feasible in its current format , needs modification or is unfeasible , and includes recruitment , adherence , follow-up and withdrawal measures .Trial registration The PREPS trial has been registered with IS RCT N ( IS RCT N 33435996 ) PURPOSE To evaluate the efficacy of preoperative vaginal cleansing using povidone-iodine solution 10 % on rates of post cesarean section ( CS ) infectious morbidities ( endometritis , febrile morbidity and wound infection ) . METHODS This prospect i ve r and omized trial was conducted among 226 pregnant women scheduled for term elective CS . Patients were equally divided into two groups by simple r and omization method . The study group had preoperative vaginal cleansing using povidone-iodine solution 10 % for about 1 min , while the control group did not . All cases received the prophylactic antibiotics and the usual abdominal scrub . Adverse post CS infectious morbidities such as endometritis , febrile morbidity and wound infection were observed at the time of hospital discharge and weekly for 6 weeks postpartum . RESULTS Both groups were matched regarding the baseline patients ' characteristics . Overall , post-CS infectious morbidity was significantly reduced from 20.7 % in the control group to 7.5 % in the intervention group . Marked significant reduction was seen in the incidence of endometritis ( 11.8 % in the control group versus 2.8 % in the intervention group ) . However , maternal fever and wound infection showed no significant difference between both groups . CONCLUSION Vaginal cleansing with povidone-iodine solution 10 % prior to elective CS appears to be effective in reducing rates of post-CS infectious morbidity mainly endometritis OBJECTIVE To develop a core outcome set of primary outcomes for studies involving cesarean deliveries with infectious morbidity outcomes . STUDY DESIGN Authors reported primary outcomes from 11 Cochrane systematic review s ( SRs ) , 12 other SRs , and 327 r and omized controlled trials ( RCTs ) . These outcomes were condensed into 20 primary outcome groups . Next , a modified Delphi technique was used to gain consensus on key outcomes . Authors from included SRs were sent a question naire consisting of a free response and multiple-choice questions . These data were used to propose a set of core outcomes . RESULTS The most frequent outcomes in RCTs were composite " infectious outcomes " ( 24 % ) with the second most common being endometritis ( 12 % ) . The most common reported SR outcomes were wound infection ( 21 % ) and endometritis ( 16 % ) . For the Delphi survey free response portion , wound infection ( 88 % ) and endometritis ( 79 % ) were the most commonly endorsed outcomes . Chosen list outcomes were maternal mortality ( 83 % ) , wound infection ( 83 % ) , wound complications ( 86 % ) , and postpartum endometritis ( 80 % ) . The proposed final core outcome set for cesarean trials was endometritis ( primary outcome ) , maternal mortality , wound infection , wound complications , febrile morbidity , and neonatal morbidity . CONCLUSION Utilizing defined core outcomes in all studies of cesarean section can harmonize trial reports and allow data synthesis for meta-analyses Summary The commonest complication associated with caesarean section is infection . The aim of this study is to investigate the effect of vaginal preparation with povidone-iodine on post-caesarean infection . In this clinical trial , 568 patients were selected for two groups : a treatment group and a control group , each with 284 patients . A vaginal scrub was performed before the routine abdominal scrub , with two 4 × 4 cm sponge sticks saturated with povidone-iodine solution , rotated in the vagina for about 30 s. In the control group , only the abdominal scrub was performed . Patients received a single dose of prophylactic antibiotics , and were review ed for 6 weeks to look for predefined variables . Post-caesarean endometritis occurred less frequently in the treatment group than in the control group ( 2.5 % vs 1.4 % ) . There was no significant difference for febrile morbidity and wound infection in the two groups . The adjusted odds ratio for endometritis after vaginal preparation was 0.03 ( 95 % CI : 0.008–0.7 ) . Vaginal preparation with povidone-iodine may decrease the risk of post-caesarean endometritis |
12,941 | 21,901,725 | There is currently no systematic evidence to guide clinical decision-making regarding the timing for closure of traumatic wounds . | BACKGROUND Acute traumatic wounds are one of the common reasons why people present to the emergency department .
Primary closure has traditionally been reserved for traumatic wounds presenting within six hours of injury and considered ' clean ' by the attending surgeon , with the rest undergoing delayed primary closure as a means of controlling wound infection .
Primary closure has the potential benefit of rapid wound healing but poses the potential threat of increased wound infection .
There is currently no evidence to guide clinical decision-making on the best timing for closure of traumatic wounds .
OBJECTIVES To determine the effect on time to healing of primary closure versus delayed closure for non bite traumatic wounds presenting within 24 hours post injury .
To explore the adverse effects of primary closure compared with delayed closure for non bite traumatic wounds presenting within 24 hours post injury . | We prospect ively studied the management and outcome of 2,834 children , aged 1 month to 18 years , who presented to the emergency department of the Children 's Hospital of Philadelphia for laceration repair . Patients with bite wounds were excluded from the study . Eight percent ( 239 ) of all patients had complications on initial evaluation ; the most common was the presence of a foreign body ( 55 ) . Infection on presentation was diagnosed in 22 cases ( 0.8 % ) . All of these patients had delayed their initial care beyond 18 hours ( range , 18 to 288 hours ; mean , 18 hours ) . Other factors significantly associated with infection on presentation included occurrence of the injury outdoors ( 16 ; P less than .001 ) , injury due to broken " street " glass ( seven ; P less than .02 ) , and injury of an extremity ( 18 ; P less than .01 ) . The rate of prerepair infection was not influenced by the size of the wound . Infections developed subsequent to initial repair in 34 cases ( 1.2 % ) . Factors associated with development of subsequent infection included use of prophylactic antibiotics , use of subcutaneous sutures , laceration length of more than 5.0 cm , glass or ice as a causative agent , and upper- or lower-extremity involvement . The majority of injuries were repaired by ED personnel without surgical consultation . Postrepair infection rates were not influenced by the specialty of the physician managing the case . Although our study was not design ed to specifically test the issue , prophylactic antibiotics were of no proven benefit in reducing infection rates in any group of patients analyzed STUDY OBJECTIVE More than 11 million patients with traumatic wounds are seen annually in emergency departments . We developed and vali date d a data registry for traumatic wounds treated in the ED . DESIGN Prospect i ve , consecutive patient enrollment with a validation cohort of a convenience sample of 100 patients . SETTING University-affiliated hospital ED . PARTICIPANTS For all patients with traumatic wounds requiring sutures , wound registry data sheets were completed at the time of initial visit using a closed- question format . Data recorded included demographic characteristics , time from injury to evaluation , pertinent medical history , wound characteristics , type of anesthesia , details of wound-cleansing methods , details of wound closure , and postoperative care . We devised a follow-up tool to evaluate for the presence of infection and short-term cosmetic appearance . Interphysician reliability was assessed for wound description , presence of infection , and cosmetic appearance by use of the kappa statistic . RESULTS A wound registry data collection instrument that takes less than 1 minute to complete and enables the collection of most wound management techniques used by emergency physicians was found to have substantial interobserver concordance for wound description ( kappa range , .55 to .97 ) , wound infection ( kappa = 1.0 ) and overall cosmetic appearance ( kappa = .61 ) . CONCLUSION The wound registry is a reliable data collection instrument that is easy to use . It may be useful as a continuous quality -improvement tool or for st and ardization of wound surveillance and treatment data to facilitate future prospect i ve studies in wound management In wounds of the h and and forearm treated within 4 h of injury , prophylactic clindamycin , in a dose of 150 mg 6‐hourly for 5 days , did not reduce the infection rate . In wounds treated after 4 h the infection rate was reduced , but not significantly so . There was a significant reduction in the infection rate comparing all wounds treated within 4 h with those treated after 4 h. Early treatment of wounds is more important than prophylactic antibiotics , although these may have a part to play where late treatment is unavoidable Introduction Primary wound closure in the management of open tibial fractures has generally been discouraged . Several prior studies suggest that infections are not caused by the initial contamination , but are instead the result of organisms acquired in the hospital . Primary wound closure after adequate wound care and fracture stabilisation could therefore be considered a reasonable option . Material s and methods We analysed 95 patients with open tibial fractures ( Gustilo– And erson type 1 to 3A ) treated with primary fracture stabilisation and either delayed wound closure ( group I ) or primary wound closure ( group II ) , with a minimum follow-up of 12 months . Results Group I included 46 patients with a mean age of 30.2 years ( 16–56 ) , and a mean follow-up of 13.5 months ( 12–18 ) . Group II included 49 patients with a mean age of 33.4 ( 18–69 ) , and a mean follow up of 13.7 months ( 12–16 ) . One infection developed in group I ( 2 % ) , and two infections developed in group II ( 4 % ) . This difference was not found to have any statistical significance . Conclusion Our results support other recent reports that the infection rate is not increased following primary wound closure after thorough debridement of less severe open fractures . The length of stay following primary closure ( group II ) was significantly shorter , and that should result in substantially more cost effective care of these serious injuries . We conclude that primary wound closure is a safe option in properly selected cases . Prospect i ve multi-centre studies are needed to further evaluate the safety and efficacy of this treatment alternative Uncertainty about the existence and duration of a " golden period " for suture repair of simple wounds led us to evaluate prospect ively the consequences of delayed primary closure on wound healing . Wounds were eligible for study if they were not grossly infected , and had no associated injuries to nerves , blood vessels , tendons , or bone . Three hundred seventy-two patients underwent suture repair ; 204 ( 54.8 % ) returned for review seven days later . The mean time from wounding to repair for all patients was 24.2 + /- 18.8 hours . Wounds closed at up to 19 hours after wounding had a significantly higher rate of healing than those closed later : 82 of 89 ( 92.1 % ) compared with 89 of 115 ( 77.4 % ) ( P less than .01 ) . Of 23 wounds sutured 48 or more hours ( mean , 65.3 ) after wounding , 18 ( 78.3 % ) were healing at follow-up . In contrast to wounds involving other body areas , the healing of head wounds was virtually independent of time from injury to repair : 42 of 44 ( 95.5 % ) wounds involving the head and repaired later than 19 hours after injury were healing , compared with 47 of 71 ( 66.2 % ) of all other wounds ( P less than .001 ) . On the basis of these data we conclude that there is a 19-hour " golden period " for repair of simple wounds involving body areas other than the head , after which sutured wounds are significantly less likely to heal , and the healing of clean , simple wounds involving the head is unaffected by the interval between injury and repair BACKGROUND / AIMS To compare two non-invasive techniques of assessing wound healing , photography and high resolution ultrasound ( HRUS ) scanning , in experimentally induced full-thickness human skin wounds . METHODS Punch biopsy wounds , 4 mm in diameter , were made aseptically through locally anaesthetised skin on the anterior ( volar ) surface of the non-dominant forearm , 3 cm below the base of the cubital fossa , of 20 human participants . The wounds were treated with a topical antibiotic and covered for 3 days with Mepore sterile dressings . Wound healing was assessed on post-operative days 3 , 7 , 14 and 21 from photographs and HRUS B-scans . All photographs were taken of the wound site and adjacent intact skin under st and ardised conditions . The prints obtained were examined visually and digitised . Digital HRUS B-scans were taken through the centre of the wound bed and the adjacent intact skin parallel to the epidermis . Using the scanner 's calibrated linear measurement capability , the wound width was measured adjacent to the deep surface of the scab , at the base of the wound , and midway between these two levels . RESULTS The wound margins were more clearly defined in the HRUS scans than in the photographs of the wounds ; in some of the latter the scab masked the wound margins . Changes in the surface width of the wound were affected by the time of scab dehiscence , which varied between volunteers . There was less individual variation in the width of the base of the wound , as measured from the HRUS scans . CONCLUSIONS In contrast to photography , which allows recording of changes in the superficial aspect of the wound only , HRUS scanning permits the quantitative assessment of structural changes deep within the wound . Temporal changes in the width of the base of the wound can be used as an indication of the progress of repair |
12,942 | 26,732,615 | The authors found that although the majority of adherence-enhancing interventions were cost-effective or cost-saving , variation exists within different intervention types . | Low patient adherence to health-related interventions is a major barrier to achieving healthcare goals and is associated with very high avoidable costs .
Although several studies suggest that adherence-enhancing interventions can improve health outcomes , economic evaluations of these interventions are scarce .
Systematic review s published to date are limited to interventions to enhance adherence to pharmaceuticals or to specific diseases and interventions .
The authors ' objective was to examine the evidence regarding the cost-effectiveness of adherence-enhancing interventions in healthcare and what conclusion could be drawn about these interventions . | Background The aim of the present study was to evaluate the cost-effectiveness of tailored print communication ( TPC ) , telephone motivational interviewing ( TMI ) , a combination of the two , and no intervention on two outcomes in adults aged 45 to 70 , half of them having hypertension : increasing the number of public health guidelines met for three behaviors ( physical activity and fruit and vegetable consumption ) , and impact on quality adjusted life years ( QALYs ) . Methods Participants ( n = 1,629 ) from 23 Dutch general practice s were r and omized into one of four groups , which received 4 TPCs , 4 TMIs , 2 of each ( combined ) , or no intervention ( control ) , respectively . The self-reported outcomes , measured at baseline and 73 weeks follow-up ( 7 months after the last intervention component ) , were difference in total number of guidelines met at follow-up compared to baseline , and number of QALYs experienced over 73 weeks . The costs of implementing the intervention were estimated using a bottom-up approach . Results At 73 weeks follow-up participants showed increased adherence with 0.62 ( TPC ) , 0.40 ( TMI ) , 0.50 ( combined ) , and 0.26 ( control ) guidelines compared to baseline , and experienced 1.09 , 1.08 , 1.08 , and 1.07 QALYs , respectively . The costs for the control group were considered to be zero . TMI was more expensive ( € 107 per person ) than both the combined intervention ( € 80 ) and TPC ( € 57 ) . The control condition was most cost-effective for lower ceiling ratios , while TPC had the highest probability of being most cost-effective for higher ceiling ratios ( more than € 160 per additional guideline met , and € 2,851 for each individual QALY ) . Conclusions For low society 's willingness to pay , the control group was most cost-effective for the number of QALYs experienced over 73 weeks . This also applied to the increase in the number of guidelines met at lower ceiling ratios , whereas at higher ceiling ratios , TPC had a higher probability of being more cost-effective than the TMI , combined or control conditions . This also seemed to apply for QALYs experienced over 73 weeks . More research is needed on the long-term efficacy of both TPC and TMI , as well as on how to increase their cost-effectiveness . Trial registration Dutch Trial Register Background Non-adherence to antihypertensive drugs is high , and the economic consequences of non-adherence may be substantial . The Medication Events Monitoring System ( MEMS ) , which is a method to improve adherence , has been shown to be a useful tool for the management of adherence problems . Objective To assess the cost effectiveness of the MEMS compared with usual care in a population of hypertensive patients with poor adherence . The MEMS programme consisted of provision of containers fitted with electronic caps together with adherence training if indicated . Methods In a r and omised controlled trial , 164 hypertensive patients in the experimental strategy and 89 patients in the usual care strategy were followed for 5 months . Patients who had a systolic blood pressure ( SBP ) ≥160 mm Hg and /or diastolic BP ( DBP ) ≥95 mm Hg despite the use of antihypertensive drugs were eligible . Patients were recruited by a GP , and treatment took place in general practice .In the experimental strategy , electronic monitoring of the intake of antihypertensive drugs was introduced without change of medication . Unsatisfactory adherence was defined as < 85 % of days with the number of doses taken as prescribed . In the usual care strategy , antihypertensive treatment was intensified by the addition or change of antihypertensive drugs , if necessary , without provision of an electronic monitor . Outcome parameters included the proportion of patients with normalised blood pressure ( NBP ) at 5 months and QALYs . Costs were quantified from the healthcare and societal perspective . Non-parametric bootstrap simulations were per formed to quantify the uncertainty around the mean estimates and cost-effectiveness acceptability curves were presented . In addition , a number of univariate sensitivity analyses were performed on deterministic variables . Results At 5 months , 3.1 % ( 95 % UI [ uncertainty interval ] −9.7 % , + 15.8 % ) more patients had NBP , and 0.003 ( 95 % UI −0.005 , + 0.010 ) more QALYs were generated in the experimental strategy . A statistically significant lower percentage of patients had a dose escalation in the experimental strategy . Irrespective of the ceiling ratio for cost effectiveness , the cost-effectiveness probability was between 75 % and 80 % for the analysis from the healthcare perspective using proportion of patients with NBP as the outcome parameter . For the analysis from the societal perspective using QALYs as the outcome parameter , this probability was between 45 % and 51 % . Conclusion For a time horizon of 5 months , a difference in both cost and effect could not be detected between an adherence-improving programme compared with usual care for hypertensive patients . The probability that the adherence-improving programme is cost effective is at best moderate . Moreover , the costeffectiveness result is surrounded with considerable uncertainty and large-scale implementation warrants additional research into the economic consequences of this intervention . Patients may benefit from the use of a MEMS monitor in situations where BP targets are not reached because of suspected non-adherence and both patient and GP are reluctant to increase the dose or number of antihypertensive drugs Background Non-adherence to anti-psychotics is common , expensive and affects recovery . We therefore examine the cost-effectiveness of adherence therapy for people with schizophrenia by multi-centre r and omised trial in Amsterdam , London , Leipzig and Verona . Methods Participants received 8 sessions of adherence therapy or health education . We measured lost productivity and use of health/social care , criminal justice system and informal care at baseline and one year to estimate and compare mean total costs from health/social care and societal perspectives . Outcomes were the Short Form 36 ( SF-36 ) mental component score ( MCS ) and quality -adjusted life years ( QALYs ) gained ( SF-36 and EuroQoL 5 dimension ( EQ5D ) ) . Cost-effectiveness was examined for all cost and outcome combinations using cost-effectiveness acceptability curves ( CEACs ) . Results 409 participants were recruited . There were no cost or outcome differences between adherence therapy and health education . The probability of adherence therapy being cost-effective compared to health education was between 0.3 and 0.6 for the six cost- outcome combinations at the willingness to pay thresholds we examined . Conclusions Adherence therapy appears equivalent to health education . It is unclear whether it would have performed differently against a treatment as usual control , whether such an intervention can impact on quality of life in the short-term , or whether it is likely to be cost-effective in some sites but not others . Trial registration Trial registration : Current Controlled TrialsIS RCT Background High levels of adherence to medications for HIV infection are essential for optimal clinical outcomes and to reduce viral transmission , but many patients do not achieve required levels . Clinician-delivered interventions can improve patients ’ adherence , but usually require substantial effort by trained individuals and may not be widely available . Computer-delivered interventions can address this problem by reducing required staff time for delivery and by making the interventions widely available via the Internet . We previously developed a computer-delivered intervention design ed to improve patients ’ level of health literacy as a strategy to improve their HIV medication adherence . The intervention was shown to increase patients ’ adherence , but it was not clear that the benefits result ing from the increase in adherence could justify the costs of developing and deploying the intervention . The purpose of this study was to evaluate the relation of development and deployment costs to the effectiveness of the intervention . Methods Costs of intervention development were drawn from accounting reports for the grant under which its development was supported , adjusted for costs primarily result ing from the project ’s research purpose . Effectiveness of the intervention was drawn from results of the parent study . The relation of the intervention ’s effects to changes in health status , expressed as utilities , was also evaluated in order to assess the net cost of the intervention in terms of quality adjusted life years ( QALYs ) . Sensitivity analyses evaluated ranges of possible intervention effectiveness and duration s of its effects , and costs were evaluated over several deployment scenarios . Results The intervention ’s cost effectiveness depends largely on the number of persons using it and the duration of its effectiveness . Even with modest effects for a small number of patients the intervention was associated with net cost savings in some scenarios and for duration s greater than three months and longer it was usually associated with a favorable cost per QALY . For intermediate and larger assumed effects and longer duration s of intervention effectiveness , the intervention was associated with net cost savings . Conclusions Computer-delivered adherence interventions may be a cost-effective strategy to improve adherence in persons treated for HIV.Trial registration Clinical trials.gov identifier NCT01304186 BACKGROUND Comprehensive geriatric assessment ( CGA ) can be effective in inpatient units , but such inpatient setting s are prohibitively expensive . If similar benefits could be obtained in outpatient setting s , CGA might be a more attractive option . OBJECTIVES To assess the cost-effectiveness ( CE ) of an outpatient geriatric assessment with an intervention to increase adherence . SUBJECTS Three hundred fifty-one community-dwelling , elderly subjects with at least one of four geriatric conditions . MEASURES In addition to the measures of functioning , we collected data on the costs of the intervention itself and on the use of medical services in the 64 weeks after the intervention . RESULTS The intervention , which prevented functional decline , cost $ 273 per participant . The intervention group averaged three more visits than the control group in the first 32 weeks after the intervention , but only 1.2 extra visits in the next 32 weeks . We estimate that the costs of these additional medical services would be $ 473 for the 5 years after the intervention , leading to a total cost per Quality Adjusted Life Year ( QALY ) of $ 10,600 . CONCLUSIONS The CE of this program compares favorably with many common medical interventions . Whether investments should be made in health care re sources on treatments that lead to modest improvements in the functioning of community-dwelling elderly people remains a societal decision Background Non-adherence to antidepressants generates higher costs for the treatment of depression . Little is known about the cost-effectiveness of pharmacist 's interventions aim ed at improving adherence to antidepressants . The study aim ed to evaluate the cost-effectiveness of a community pharmacist intervention in comparison with usual care in depressed patients initiating treatment with antidepressants in primary care . Methods Patients were recruited by general practitioners and r and omized to community pharmacist intervention ( 87 ) that received an educational intervention and usual care ( 92 ) . Adherence to antidepressants , clinical symptoms , Quality -Adjusted Life-Years ( QALYs ) , use of healthcare services and productivity losses were measured at baseline , 3 and 6 months . Results There were no significant differences between groups in costs or effects . From a societal perspective , the incremental cost-effectiveness ratio ( ICER ) for the community pharmacist intervention compared with usual care was € 1,866 for extra adherent patient and € 9,872 per extra QALY . In terms of remission of depressive symptoms , the usual care dominated the community pharmacist intervention . If willingness to pay ( WTP ) is € 30,000 per extra adherent patient , remission of symptoms or QALYs , the probability of the community pharmacist intervention being cost-effective was 0.71 , 0.46 and 0.75 , respectively ( societal perspective ) . From a healthcare perspective , the probability of the community pharmacist intervention being cost-effective in terms of adherence , QALYs and remission was of 0.71 , 0.76 and 0.46 , respectively , if WTP is € 30,000 . Conclusion A brief community pharmacist intervention addressed to depressed patients initiating antidepressant treatment showed a probability of being cost-effective of 0.71 and 0.75 in terms of improvement of adherence and QALYs , respectively , when compared to usual care . Regular implementation of the community pharmacist intervention is not recommended . Trial Registration Clinical Trials.gov Background Smoking prevalence is high among Pakistani and Bangladeshi men in the UK , but there are few tailored smoking cessation programmes for Pakistani and Bangladeshi communities . The aim of this study was to pilot a cluster r and omised controlled trial comparing the effectiveness of Pakistani and Bangladeshi smoking cessation outreach workers with st and ard care to improve access to and the success of English smoking cessation services . Methods A pilot cluster r and omised controlled trial was conducted in Birmingham , UK . Geographical lower layer super output areas were used to identify natural communities where more than 10 % of the population were of Pakistani and Bangladeshi origin . 16 agglomerations of super output areas were r and omised to normal care controls vs. outreach intervention . The number of people setting quit date s using NHS services , vali date d abstinence from smoking at four weeks , and stated abstinence at three and six months were assessed . The impact of the intervention on choice and adherence to treatments , attendance at clinic appointments and patient satisfaction were also assessed . Results We were able to r and omise geographical areas and deliver the outreach worker-based services . More Pakistani and Bangladeshi men made quit attempts with NHS services in intervention areas compared with control areas , rate ratio ( RR ) 1.32 ( 95%CI : 1.03 - 1.69 ) . There was a small increase in the number of 4-week abstinent smokers in intervention areas ( RR 1.30 , 95%CI : 0.82 - 2.06 ) . The proportion of service users attending weekly appointments was lower in intervention areas than control areas . No difference was found between intervention and control areas in choice and adherence to treatments or patient satisfaction with the service . The total cost of the intervention was £ 124,000 ; an estimated cost per quality -adjusted life year ( QALY ) gained of £ 8,500 . Conclusions The intervention proved feasible and acceptable . Outreach workers exp and ed reach of smoking cessation services in diverse locations of relevance to Pakistani and Bangladeshi communities . The outreach worker model has the potential to increase community cessation rates and could prove cost-effective , but needs evaluating definitively in a larger , appropriately powered , r and omised controlled trial . These future trials of outreach interventions need to be of sufficient duration to allow embedding of new models of service delivery . Trial registration Current Controlled Trials IS RCT Background . There is increasing evidence highlighting the effectiveness of patient decision aids ( PtDAs ) , but evidence supporting their cost-effectiveness is lacking . We consider patients with obstructive sleep apnea ( OSA ) , in whom a PtDA may decrease nonadherence to treatment by empowering patients to receive the option that is most congruent with their own values . Objective . To determine the potential costs and benefits of delivering a PtDA to patients with moderate OSA . Methods . A Markov cohort decision-analytic model was developed for patients with moderate OSA , comparing a PtDA to usual care over 5 years from a societal perspective . Data for patient preference for treatment options was taken from a recent r and omized crossover trial , event data ( cardiovascular , motor vehicle accidents ) came from national data bases and published literature . Potential improvements in adherence are unknown , so we considered a realistic range of values . Outcome measures were 5-year costs ( in 2010 Canadian dollars ) , quality -adjusted life years ( QALYs ) , and the incremental cost-effectiveness ratio ( ICER ) . Results . When adherence to treatment was unchanged , the PtDA strategy was dominated by incurring lower QALYs and higher costs . When nonadherence was decreased by 20 % in the PtDA arm ( corresponding to an increase in adherence from 63 % to 70 % for continuous positive airway pressure and from 77 % to 82 % for m and ibular advancement splints in year 1 ) , the ICER fell to $ 62,414/QALY . Costs associated with the treatment devices and delivering the PtDA had the greatest effect on cost-effectiveness . Limitations . The model relies on surrogate measures and opinions for key parameters . Conclusions : The cost-effectiveness of PtDAs will depend on context ual factors , but a framework is described for properly considering their long-term cost-effectiveness . A number of important questions around the appropriateness of benefit measurement for PtDA trials are highlighted Abstract Objective : Although the use of innovative drug delivery systems , like orally disintegrating antipsychotic tablets ( ODT ) , may facilitate medication adherence and help reduce the risk of relapse and hospitalization , no information is available about the comparative cost-effectiveness of st and ard oral tablets ( SOT ) vs ODT formulations in the treatment of schizophrenia . This study compared the cost-effectiveness of olanzapine ODT and olanzapine SOT in the usual treatment of out patients with schizophrenia from a US healthcare perspective . The study also compared olanzapine ODT with risperidone and aripiprazole , two other atypical antipsychotics available in both ODT and SOT formulations . Methods : Published medical literature and a clinical expert panel were used to populate a 1-year Monte Carlo Micro-simulation model . The model captures clinical and cost parameters including adherence levels , treatment discontinuation by reason , relapse with and without inpatient hospitalization , quality -adjusted life years ( QALYs ) , treatment-emergent adverse events , healthcare re source utilization , and associated costs . Key outcomes were total annual direct cost per treatment , QALY , and incremental cost-effectiveness ( ICER ) per 1 QALY gained . Results : Based on model projections , olanzapine ODT therapy was more costly ( $ 9808 vs $ 9533 ) , but more effective in terms of a lower hospitalization rate ( 15 % vs 16 % ) and better QALYs ( 0.747 vs 0.733 ) than olanzapine SOT therapy . Olanzapine ODT was more cost-effective than olanzapine SOT ( ICER : $ 19,643 ) , more cost-effective than risperidone SOT therapy ( ICER : $ 39,966 ) , and dominant ( meaning less costly and more effective ) than risperidone ODT and aripiprazole in ODT or SOT formulations . Limitations : Lack of head-to-head r and omized studies comparing the three studied atypical antipsychotics required making input assumptions that need further study . Conclusions : This micro-simulation found that the utilization of olanzapine ODT for the treatment of schizophrenia is predicted to be more cost-effective than any other ODT or SOT formulations of the studied atypical antipsychotic medications BACKGROUND & AIMS Adherence to antiviral treatment is important to achieve sustained virological response ( SVR ) in chronic hepatitis C ( CHC ) . We evaluated the efficiency of a multidisciplinary support programme ( MSP ) , based on published HIV treatment experience , to increase patient adherence and the efficacy of pegylated interferon alfa-2a and ribavirin in CHC . METHODS 447 patients receiving antiviral treatment were distributed into 3 groups : control group ( 2003 - 2004 , n=147 ) , MSP group ( 2005 - 2006 , n=131 ) , and MSP-validation group ( 2007 - 2009 , n=169 ) . The MSP group included two hepatologists , two nurses , one pharmacist , one psychologist , one administrative assistant , and one psychiatrist . Cost-effectiveness analysis was performed using a Markov model . RESULTS Adherence and SVR rates were higher in the MSP ( 94.6 % and 77.1 % ) and MSP-validation ( 91.7 % and 74.6 % ) groups compared to controls ( 78.9 % and 61.9 % ) ( p<0.05 in all cases ) . SVR was higher in genotypes 1 or 4 followed by the MSP group vs. controls ( 67.7 % vs. 48.9 % , p=0.02 ) compared with genotypes 2 or 3 ( 87.7 % vs. 81.4 % , p = n.s . ) . The MSP was the main predictive factor of SVR in patients with genotype 1 . The rate of adherence in patients with psychiatric disorders was higher in the MSP groups ( n=95 , 90.5 % ) compared to controls ( n=28 , 75.7 % ) ( p=0.02 ) . The cost per patient was € 13,319 in the MSP group and € 16,184 in the control group . The MSP group achieved more quality -adjusted life years ( QALYs ) ( 16.317 QALYs ) than controls ( 15.814 QALYs ) and was dominant in all genotypes . CONCLUSIONS MSP improves patient compliance and increases the efficiency of antiviral treatment in CHC , being cost-effective Background In HIV-infected pregnant women , viral suppression prevents mother-to-child HIV transmission . Directly observed highly-active antiretroviral therapy ( HAART ) enhances virological suppression , and could prevent transmission . Our objective was to project the effectiveness and cost-effectiveness of directly observed administration of antiretroviral drugs in pregnancy . Methods and Findings A mathematical model was created to simulate cohorts of one million asymptomatic HIV-infected pregnant women on HAART , with women r and omly assigned self-administered or directly observed antiretroviral therapy ( DOT ) , or no HAART , in a series of Monte Carlo simulations . Our primary outcome was the quality -adjusted life expectancy in years ( QALY ) of infants born to HIV-infected women , with the rates of Caesarean section and HIV-transmission after DOT use as intermediate outcomes . Both self-administered HAART and DOT were associated with decreased costs and increased life-expectancy relative to no HAART . The use of DOT was associated with a relative risk of HIV transmission of 0.39 relative to conventional HAART ; was highly cost-effective in the cohort as a whole ( cost-utility ratio $ 14,233 per QALY ) ; and was cost-saving in women whose viral loads on self-administered HAART would have exceeded 1000 copies/ml . Results were stable in wide-ranging sensitivity analyses , with directly observed therapy cost-saving or highly cost-effective in almost all cases . Conclusions Based on the best available data , programs that optimize adherence to HAART through direct observation in pregnancy have the potential to diminish mother-to-child HIV transmission in a highly cost-effective manner . Targeted use of DOT in pregnant women with high viral loads , who could otherwise receive self-administered HAART would be a cost-saving intervention . These projections should be tested with r and omized clinical trials BACKGROUND Improved compliance in active ulcerative colitis ( UC ) is likely to improve healthcare efficiency by reducing time spent in active mild to moderate UC state . To establish whether once daily ( OD ) mesalazine offers economic advantages over twice daily ( BD ) dosing in active UC , we evaluated the outcomes and costs of a recently published r and omized study . METHODS A cost-effectiveness model with four week Markov cycles was developed to reflect current treatment practice s in the Netherl and s with OD and BD mesalazine for active UC . The health service perspective of the Netherl and s was reflected in the model and considered a 32week time horizon with 4 weekly Markov cycles . Outcomes evaluated in the model were time spent in active and remission UC and the corresponding health-related quality of life associated with different clinical states . This was then used to derive quality adjusted life-years ( QALYs ) at each treatment stage . RESULTS A greater proportion of subjects on 4 g OD achieved remission at weeks 4 and 8 compared with 2 g BD . After 32 weeks the average costs per patient with active UC were € 3097 and € 3548 for those treated with OD and BD mesalazine respectively , with an average saving of € 451 per patient treated with OD mesalazine . The average costs per QALY for OD and BD mesalazine were € 5433 and € 6324 for OD and BD , respectively . CONCLUSIONS Based on the results from a single r and omized study , OD dosing result ed in a shorter time spent in active UC which result ed in lower healthcare costs BACKGROUND AND AIMS St and ard practice to maintain remission in ulcerative colitis ( UC ) consists of daily mesalazine therapy . However , frequent dosing is associated with poor adherence and increased failure rates . The PODIUM ( Pentasa ™ Once Daily In UC Maintenance ) r and omised control trial showed 2 g once daily ( OD ) to be superior to twice daily ( BD ) dosing for maintaining remission . We sought to determine whether this alternative dosing regimen is cost-effective . METHODS An economic evaluation was conducted to compare costs and outcomes of OD with twice daily ( BD ) dosing . The main outcome considered was quality -adjusted life years ( QALYs ) based on health state utilities derived from the primary outcome measure , remission without relapse at 12 months defined by a UCDAI score ≤1 . The economic evaluation consisted of two health states : ( 1 ) remission and ( 2 ) active UC . RESULTS Annual average treatment costs for OD and BD dosing were £ 654 ( 95 % CI : £ 536-£759 ) and £ 747 ( £ 620-£860 ) , respectively with an average per person savings of £ 93 per year . Average annual costs of ancillary care for relapse for OD and BD dosing were £ 307 ( £ 241-£383 ) and £ 396 ( £ 320-£483 ) , respectively . Treatment with OD 2 g mesalazine result ed in an incremental QALY improvement of 0.004 units , indicating that it was the dominant treatment option ( i.e. improved outcomes and cost-saving ) . Variations in parameter estimates in the sensitivity analysis indicated that mesalazine had > 0.95 probability of being cost-effective compared to BD based on accepted willingness to pay thresholds applied by the UK National Health Service . CONCLUSIONS Once daily 2 g mesalazine for maintaining remission in UC is cost-saving compared with 1 g twice daily . Cost-savings with 2 g once daily were achieved by differences in ancillary care attributed to higher failure rates observed with 1 g twice daily Introduction Older patients with fragility fractures are not commonly tested or treated for osteoporosis . Compared to usual care , a previously reported intervention led to 30 % absolute increases in osteoporosis treatment within 6 months of wrist fracture . Our objective was to examine longer-term outcomes , reproducibility , and cost-effectiveness of this intervention . Methods We conducted an extended analysis of a non-r and omized controlled trial with blinded ascertainment of outcomes that compared a multifaceted intervention to usual care controls . Patients > 50 years with a wrist fracture treated in two Emergency Departments in the province of Alberta , Canada were included ; those already treated for osteoporosis were excluded . Overall , 102 patients participated in this study ( 55 intervention and 47 controls ; median age : 66 years ; 78 % were women ) . The interventions consisted of faxed physician reminders that contained osteoporosis treatment guidelines endorsed by opinion leaders and patient counseling . Controls received usual care ; at 6-months post-fracture , when the original trial was completed , all controls were crossed-over to intervention . The main outcomes were rates of osteoporosis testing and treatment within 6 months ( original study ) and 1 year ( delayed intervention ) of fracture , and 1-year persistence with treatments started . From the perspective of the healthcare payer , the cost-effectiveness ( using a Markov decision-analytic model ) of the intervention was compared with usual care over a lifetime horizon . Results Overall , 40 % of the intervention patients ( vs. 10 % of the controls ) started treatment within 6 months post-fracture , and 82 % ( 95%CI : 67–96 % ) had persisted with it at 1-year post-fracture . Delaying the intervention to controls for 6 months still led to equivalent rates of bone mineral density ( BMD ) testing ( 64 vs. 60 % in the original study ; p = 0.72 ) and osteoporosis treatment ( 43 vs. 40 % ; p = 0.77 ) as previously reported . Compared with usual care , the intervention strategy was dominant – per patient , it led to a $ 13 Canadian ( U.S. $ 9 ) cost savings and a gain of 0.012 quality -adjusted life years . Base-case results were most sensitive to assumptions about treatment cost ; for example , a 50 % increase in the price of osteoporosis medication led to an incremental cost-effectiveness ratio of $ 24,250 Canadian ( U.S. $ 17,218 ) per quality -adjusted life year gained . Conclusions A pragmatic intervention directed at patients and physicians led to substantial improvements in osteoporosis treatment , even when delivered 6-months post-fracture . From the healthcare payer ’s perspective , the intervention appears to have led to both cost-savings and gains in life expectancy PURPOSE Assess the costs and cost-effectiveness of an incentive-based tuberculosis ( TB ) program design ed to promote adolescents ' compliance with treatment for latent TB infection ( LTBI ) . METHODS R and omized controlled trial . Adolescents between the ages of 11 and 19 years who were referred to one of two participating clinics after being screened for TB and receiving a positive diagnosis indicating LTBI ( n = 794 ) were assigned to one of four groups : usual care , peer counseling , contingency contracting , and combined peer counseling/contingency contracting . Primary outcome variables were completion of isoniazid preventive therapy ( IPT ) , total treatment costs , and lifetime TB-related costs per quality -adjusted life year ( QALY ) in each of the four study groups ( three treatment , one control ) . Cost effectiveness was evaluated using a five-stage Markov model and a Monte Carlo simulation with 10,000 trials . RESULTS Average costs were 199 dollars for usual care ( UC ) , 277 dollars for peer counseling ( PC ) , 326 dollars for contingency contracting ( CC ) , and 341 dollars for PC + CC combined . The differences among these groups were all significant at the p = .001 level . Only the PC + CC group improved the rate of IPT completion ( 83.8 % ) relative to usual care ( 75.9 % ) ( p = .051 ) , with an overall incremental CE ratio of 209 dollars per QALY relative to usual care . CONCLUSION Incentives combined with peer counseling are a cost-effective strategy for helping adolescents to complete care when combined with peer counseling OBJECTIVES We report the 10-year effectiveness and within-trial cost-effectiveness of the Diabetes Prevention Program ( DPP ) and its Outcomes Study ( DPPOS ) interventions among participants who were adherent to the interventions . STUDY DESIGN DPP was a 3-year r and omized clinical trial followed by 7 years of open-label modified intervention follow-up . METHODS Data on re source utilization , cost , and quality of life were collected prospect ively . Economic analyses were performed from health system and societal perspectives . Lifestyle adherence was defined as achieving and maintaining a 5 % reduction in initial body weight , and metformin adherence as taking metformin at 80 % of study visits . RESULTS The relative risk reduction was 49.4 % among adherent lifestyle participants and 20.8 % among adherent metformin participants compared with placebo . Over 10 years , the cumulative , undiscounted , per capita direct medical costs of the interventions , as implemented during the DPP , were greater for adherent lifestyle participants ( $ 4810 ) than adherent metformin participants ( $ 2934 ) or placebo ( $ 768 ) . Over 10 years , the cumulative , per capita non-interventionrelated direct medical costs were $ 4250 greater for placebo participants compared with adherent lifestyle participants and $ 3251 greater compared with adherent metformin participants . The cumulative quality -adjusted life-years ( QALYs ) accrued over 10 years were greater for lifestyle ( 6.80 ) than metformin ( 6.74 ) or placebo ( 6.67 ) . Without discounting , from a modified societal perspective ( excluding participant time ) and a full societal perspective ( including participant time ) , lifestyle cost < $ 5000 per QALY-gained and metformin was cost saving compared with placebo . CONCLUSIONS Over 10 years , lifestyle intervention and metformin were cost-effective or cost saving compared with placebo . These analyses confirm that lifestyle and metformin represent a good value for money Summary : Adherence to antiretroviral medications has been shown to be an important factor in predicting viral suppression and clinical outcomes . The objective of this analysis was to assess the cost-effectiveness of a nursing intervention on antiretroviral adherence using data from a r and omized controlled clinical trial as input to a computer-based simulation model of HIV disease . For a cohort of HIV-infected patients similar to those in the clinical trial ( mean initial CD4 count of 319 cells/mm3 ) , implementing the nursing intervention in addition to st and ard care yielded a 63 % increase in virologic suppression at 48 weeks . This produced increases in expected survival ( from 94.5 to 100.9 quality -adjusted life months ) and estimated discounted direct lifetime medical costs ( $ 253,800 to $ 261,300 ) . The incremental cost-effectiveness ratio for the intervention was $ 14,100 per quality -adjusted life year gained compared with st and ard care . Adherence interventions with modest effectiveness are likely to provide long-term survival benefit to patients and to be cost-effective compared with other uses of HIV care funds BACKGROUND It has been demonstrated in previous studies that pharmacist management of patients with type 2 diabetes mellitus ( T2DM ) in the outpatient setting not only improves diabetes-related clinical outcomes such as hemoglobin A1c but also blood pressure ( BP ) , total cholesterol ( TC ) , and quality of life . Improved control of BP and TC has been shown to reduce the risks of cardiovascular disease ( CVD ) , which has placed a heavy economic burden on the health care system . However , no study has evaluated the cost-effectiveness of pharmacist intervention programs with respect to the long-term preventive effects on CVD outcomes among T2DM patients . OBJECTIVES To ( a ) quantify the long-term preventive effects of pharmacist intervention on CVD outcomes among T2DM patients using evidence from a matched cohort study in the outpatient primary care setting and ( b ) assess the relative cost-effectiveness of adding a clinical pharmacist to the primary care team for the management of patients with T2DM based on improvement in CVD risks with the aid of an economic model . METHODS Clinical data between the periods of June 2007 to February 2010 were collected from electronic medical records at 2 separate clinics at Kaiser Permanente ( KP ) Northern California , 1 with primary care physicians only ( control group ) and the other with the addition of a pharmacist ( enhanced care group ) . Patients in the enhanced care group were matched 1:1 with patients in the control group according to baseline characteristics that included age , gender , A1c , and Charlson comorbidity score . The estimated 10-year CVD risk for both groups was calculated by the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) Risk Engine ( version 2 ) based on age , sex , race , smoking status , atrial fibrillation , duration of diabetes , levels of A1c , systolic BP ( SBP ) and TC , and high-density lipoprotein cholesterol ( HDL-C ) observed at 12 months . There was no statistical difference in the baseline clinical inputs to the Risk Engine ( A1c [ P=0.115 ] , SBP [ P=0.184 ] , TC [ P=0.055 ] , and HDL-C [ P=0.475 ] ) between the 2 groups . A Markov model was developed to simulate the estimated CVD outcomes over 10 years and to estimate cost-effectiveness . The final outcomes examined included incremental cost and effectiveness measured by life years and per quality -adjusted life year gained . Both deterministic sensitivity analysis ( SA ) and probabilistic SA were conducted to examine the robustness of the results . RESULTS The estimated risks for coronary heart disease ( CHD ) and stroke ( both nonfatal and fatal ) at the end of the follow-up were consistently lower in the enhanced care group compared with the control group , even though baseline risks in both groups were similar . The absolute risk reduction ( ARR ) between the enhanced care and control groups increased over time . For example , the ARR for nonfatal CHD risk in year 1 was 0.5 % ( 1.2 % vs. 0.7 % ) , whereas the ARR increased to 5.5 % in year 10 ( 14.8 % vs. 9.3 % ) . Similarly , the ARR between the enhanced care and the control groups was calculated as 0.3 % for fatal CHD in year 1 and increased to 4.6 % in year 10 . Results from the Markov model suggest that the enhanced care group was shown to be a dominant strategy ( less expensive and more effective ) compared with the control group in the 10-year evaluation period in the base-case ( average or mean results ) scenario . Sensitivity analysis that took into account the uncertainty in all important variables , such as wage of pharmacists , utility weight ( the degree of preference individuals have for a particular health state or condition ) , response rate to pharmacists ' care , and uncertainty associated with the estimated 10 years of CVD risk , revealed that the relative value of enhanced care was robust to most of the variations in these parameters . Notably , the level of cost-effectiveness measured by net monetary value depends on the time horizon adopted by the payers and the magnitude of CVD risk reduction . The enhanced care group has a higher chance of being considered as a cost-effective strategy when a longer time horizon such as a minimum of 4 to 5 years is adopted . CONCLUSIONS Adding pharmacists to the health care management team for diabetic patients improves the long-term CVD risks . The longer-term CVD risk reductions were shown to be more dramatic than the short-term reduction . A longer time horizon adopted by health plans in managing T2DM patients has a higher probability of making the intervention cost-effective Background The Wales National Exercise Referral Scheme ( NERS ) is a 16-week programme including motivational interviewing , goal setting and relapse prevention . Method A pragmatic r and omised controlled trial with nested economic evaluation of 2160 inactive participants with coronary heart disease risk ( CHD , 1559 , 72 % ) , mild to moderate depression , anxiety or stress ( 79 , 4 % ) or both ( 522 , 24 % ) r and omised to receive ( 1 ) NERS or ( 2 ) normal care and brief written information . Outcome measures at 12 months included the 7-day physical activity recall , the hospital anxiety and depression scale . Results Ordinal regression identified increased physical activity among those r and omised to NERS compared with those receiving normal care in all participants ( OR 1.19 , 95 % CI 0.99 to 1.43 ) , and among those referred for CHD only ( OR 1.29 , 95 % CI 1.04 to 1.60 ) . For those referred for mental health reason alone , or in combination with CHD , there were significantly lower levels of anxiety ( OR −1.56 , 95 % CI −2.75 to −0.38 ) and depression ( OR −1.39 , 95 % CI −2.60 to −0.18 ) , but no effect on physical activity . The base-case incremental cost-effectiveness ratio was £ 12 111 per quality adjusted life year , falling to £ 9741 if participants were to contribute £ 2 per session . Conclusions NERS was effective in increasing physical activity among those referred for CHD risk only . Among mental health referrals , NERS did not influence physical activity but was associated with reduced anxiety and depression . Effects were dependent on adherence . NERS is likely to be cost effective with respect to prevailing payer thresholds . Trial registration Current Controlled Trials IS RCT N47680448 ABSTRACT Objective : Studies have shown that weekly bisphosphonate dosing results in improved persistence compared to daily dosing among patients with postmenopausal osteoporosis , yet more than 50 % of patients discontinue therapy within a year . An oral , less frequent administration bisphosphonate provides an opportunity to improve persistence , a parameter not well modeled in previous cost-effectiveness analyses of osteoporosis therapies . Research design and methods : We developed a Markov model to estimate the effect of improved persistence on the cost-effectiveness of bisphosphonates among postmenopausal women with established osteoporosis ( vertebral fracture and bone mineral density T-score ≤ –2.5 ) and an average age of 78 years . Fracture risks , clinical efficacy , mortality , re source use , costs , and utilities were obtained from the published literature . Persistence rates were derived primarily from a published clinical trial . Approximately 50 % greater persistence with a monthly versus a weekly therapy was assumed on the basis of the PERSIST study , a 6-month , r and omized , head-to-head prospect i ve study that investigated treatment persistence in postmenopausal osteoporotic women on monthly versus weekly bisphosphonate therapy . Persistence was extrapolated to a maximum of 5 years . Following discontinuation , treatment benefit declined linearly and proportionally to the duration of active treatment . Results : Based on model estimates , more fractures were avoided ( versus no treatment ) with monthly bisphosphonate ( 58.1 per 1000 treated women ) than with weekly bisphosphonates ( 33.8 per 1000 treated women ) , result ing in lower fracture care costs per woman ( $ 7317 and $ 7548 , respectively ) . The incremental cost per quality -adjusted life-year gained was lower with a monthly bisphosphonate ( $ 13 749 ) than with weekly bisphosphonates ( $ 16 657 ) when compared to no treatment . The incremental cost per quality -adjusted life-year of a monthly bisphosphonate was $ 9476 when compared to a weekly bisphosphonate . Conclusions : In postmenopausal women with established osteoporosis , improvement in persistence with a less frequently administered oral bisphosphonate therapy could augment the fracture benefit and thereby improve cost-effectiveness . Further studies are required to refine the estimates of cost-effectiveness in order to address limited availability of adherence and fracture risk data |
12,943 | 32,033,183 | Thirty empirical studies met our inclusion criteria , including 28 adult and 2 child and adolescent sample s. The findings show that attachment security priming improved positive affect and reduced negative affect relative to control primes .
Importantly , repeated priming studies showed a cumulative positive effect of security priming over time .
We conclude that repeated priming study design s may be the most effective . | : Attachment security priming has been extensively used in relationship research to explore the contents of mental models of attachment and examine the benefits derived from enhancing security .
This systematic review explores the effectiveness of attachment security priming in improving positive affect and reducing negative affect in adults and children . | 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 Using an affective priming procedure ( S. T. Murphy & R. B. Zajonc , 1993 ) , 7 studies examined the effects of the context ual activation of representations of attachment security ( secure base schema ) on the evaluation of neutral stimuli under either neutral or stressful context s. In all the studies , participants also reported on their attachment style . Results indicated that the subliminal priming of secure base representations led to more positive affective reactions to neutral stimuli than did the subliminal priming of neutral or no pictures under both neutral and stressful context s. Although the subliminal priming of positively valued , attachment-unrelated representations heightened positive evaluations under neutral context s , it failed to elicit positive affect under stressful context s. The results also revealed interesting effects of attachment style . The discussion focuses on the affective component of the secure base schema Two studies investigated how context ually activating attachment relationships influences the working self-concept in terms of agency and communion . In Study 1 , 245 participants were primed with a secure , avoidant , or anxious-ambivalent relationship and the implicit accessibility of agency and communion was assessed using word fragments . Activating a secure relationship increased the accessibility of communion , whereas activating an anxious-ambivalent relationship increased the accessibility of agency . In Study 2 , 123 participants were primed with a secure , preoccupied , avoidant-dismissive , or avoidant-fearful relationship and explicit self-perceptions of agency and communion traits were assessed using the Extended Personality Attributes Question naire ( EPAQ ) . Gender interacted with the attachment prime , such that men primed with a secure relationship reported higher communion than did men primed with an avoidant ( dis-missive or fearful ) relationship , whereas women primed with an anxious ( preoccupied or fearful ) relationship reported higher agency than did women primed with a secure relationship Ninety 6- and 7-year-olds ( 49.3 % White , mostly middle class ) from greater Washington , DC were r and omly assigned to a subliminal priming condition ( secure , happy , or neutral ) to determine if attachment security priming decreases physiological , expressive , and self-reported fear reactions to threatening stimuli . Dispositional attachment security was also assessed . Secure priming and attachment security each decreased electrodermal reactivity , increased vagal augmentation , and decreased fearful facial expressions compared to control conditions . Examination of a statistical interaction between security priming and child attachment indicated that , although secure children had increased vagal augmentation and fewer fearful expressions than insecure children , the effects of priming were constant across secure and insecure children . There were no priming or attachment effects associated with children 's self-reported fear |
12,944 | 21,098,761 | No benefit was observed in patients with hormone receptor-positive tumors .
Dose-dense chemotherapy results in better overall and disease-free survival , particularly in women with hormone receptor-negative breast cancer . | BACKGROUND Dose-dense chemotherapy has become a mainstay regimen in the adjuvant setting for women with high-risk breast cancer .
We performed a systematic review and meta- analysis of the existing data from r and omized controlled trials regarding the efficacy and toxicity of the dose-dense chemotherapy approach in nonmetastatic breast cancer . | We evaluated the survival benefit , safety , feasibility , and tolerability of dose-dense ( DD ) adjuvant chemotherapy with epirubicin and paclitaxel for women with node-positive primary breast cancer . R and omised patients ( n=216 ) received DD or conventional-schedule ( CS ) chemotherapy . Dose-dense regimen patients ( n=108 ) received epirubicin 90 mg m−2 plus paclitaxel 175 mg m−2 in four 14-day cycles , then cyclophosphamide 600 mg m−2 , methotrexate 40 mg m−2 , and fluorouracil 600 mg m−2 ( CMF 600/40/600 ) in three 14-day cycles , plus filgrastim 5 μg kg day−1 as growth support in every cycle . Conventional-schedule regimen patients ( n=108 ) received epirubicin 90 mg m−2 plus cyclophosphamide 600 mg m−2 in four 21-day cycles , then CMF 600/40/600 in three 21-day cycles , plus filgrastim if required . After a median follow-up of 38.4 months , 71 patients ( 33 % ) relapsed or died : DD , 33 patients ( 15 deaths ) ; CS , 38 patients ( 22 deaths ) . Dose dense showed a trend for improved disease-free survival ( DFS ) and overall survival ( OS ) . Four-year rates of DFS and OS were 64 and 85 % for DD , and 58 and 75 % for CS . All seven cycles were administered to 208 patients ( 96 % ) . Rates of cycle delay , discontinuation , dose reduction , and adverse events were similar in both groups . Dose-dense sequential chemotherapy with epirubicin/paclitaxel then CMF , supported by filgrastim , is safe and improves survival for patients with node-positive breast cancer BACKGROUND Preoperative chemotherapy is a recommended treatment of both primary operable and locally advanced breast cancer . Strategies to improve efficacy include the use of anthracyclines , taxanes , and intensified dose with bone marrow support . PATIENTS AND METHODS Patients received neoadjuvant epirubicin 90 mg/m(2 ) plus cyclophosphamide 600 mg/m(2 ) followed by paclitaxel 175 mg/m(2 ) ( EC→T ) , each 3-weekly for four cycles ( n = 370 ) , or epirubicin 150 mg/m(2 ) followed by paclitaxel 225 mg/m(2 ) with pegfilgrastim followed by CMF ( cyclophosphamide 500 mg/m(2 ) , methotrexate 40 mg/m(2 ) , fluorouracil 600 mg/m(2 ) ) on days 1 and 8 ( E(dd)→T(dd)→CMF ) , each 2-weekly and for three cycles ( n = 363 ) . Patients were r and omly allocated to either simultaneous darbepoetin alfa ( DA ) ( n = 356 ) or none ( n = 377 ) . RESULTS Pathological complete response ( pCR ) rate ( breast ) was higher with E(dd)→T(dd)→CMF , 18.7 % versus 13.2 % with EC→T ; P = 0.043 , ypT0/Tis ; ypN0 was reported in 20.9 % versus 14.3 % respectively ; P = 0.019 . Patients with grade 3 tumors and negative hormone receptor status had a significantly higher pCR rate . Mean hemoglobin values maintained higher with DA ( 13.6 versus 12.6 g/dl ) . E(dd)→T(dd)→CMF regimen showed more grade 3 - 4 mucositis , sensory neuropathy , and neurological complaints . Thromboembolic events were more frequent on DA ( 3 % versus 6 % ; P = 0.055 ) . CONCLUSION Dose-dense and -intensified neoadjuvant chemotherapy with E(dd)→T(dd)→CMF was potentially superior to EC→T in terms of pCR . Primary use of DA did not affect pCR BACKGROUND To determine whether a dose-dense regimen improves outcome in early breast cancer patients , we compared outcomes with the same fluorouracil , epirubicin , and cyclophosphamide ( FEC ) chemotherapeutic regimen administered every 3 weeks ( FEC21 ) or administered every 2 weeks ( FEC14 including support with filgrastim , a granulocyte colony-stimulating factor ) in a multicenter phase III r and omized trial . METHODS A total of 1214 patients with early-stage breast cancer were r and omly assigned to receive six cycles of FEC14 ( 604 patients ) or of FEC21 ( 610 patients ) . Study endpoints were overall survival and event-free survival . Associations were assessed by multivariable analysis with adjustment for age ; tumor size ; grade ; proliferative rate ; and menopausal , lymph node , estrogen receptor , and progesterone receptor status . All statistical tests were two-sided . RESULTS Patients in the FEC14 arm had fewer dose reductions or treatment delays or discontinuation ( 26 % ) than those in the FEC21 arm ( 33 % ) ( difference = 7 % , 95 % confidence interval [ CI ] = 2 % to 12 % ; P = .008 ) . FEC14 therapy , compared with FEC21 therapy , was associated with more asthenia ( 36 % versus 29 % , difference = 7 % , 95 % CI = 2 % to 12 % ; P = .01 ) , bone pain ( 33 % versus 4 % , difference = 29 % , 95 % CI = 25 % to 33 % ; P < .001 ) , anemia ( 38 % versus 19 % , difference = 19 % , 95 % CI = 14 % to 24 % ; P < .001 ) , and thrombocytopenia ( 8 % versus 2 % , difference = 6 % , 95 % CI = 4 % to 9 % ; P < .001 ) , but with less leukopenia ( 12 % versus 45 % , difference = 33 % , 95 % CI = 28 % to 37 % ; P < .001 ) . No acute myelogenous leukemia or myelodysplastic syndrome was observed . At a median follow-up of 10.4 years , no statistically significant difference in the hazard of death ( hazard ratio [ HR ] = 0.87 , 95 % CI = 0.67 to 1.13 ) or recurrence ( HR = 0.88 , 95 % CI = 0.71 to 1.08 ) was found between FEC14 and FEC21 groups after adjustment by multivariable analysis . Although the study was underpowered for subset analysis , we found no evidence that the effect of the treatment type was associated with any of the potential prognostic factors . CONCLUSION Our results support the long-term safety of FEC14 chemotherapy as an adjuvant treatment of breast cancer . However , this therapy was not associated with improved outcome , but because of the limited statistical power of our study , we can not rule out a modest improvement in outcome associated with FEC14 therapy PURPOSE Using a 2 x 2 factorial design , we studied the adjuvant chemotherapy of women with axillary node-positive breast cancer to compare sequential doxorubicin ( A ) , paclitaxel ( T ) , and cyclophosphamide ( C ) with concurrent doxorubicin and cyclophosphamide ( AC ) followed by paclitaxel ( T ) for disease-free ( DFS ) and overall survival ( OS ) ; to determine whether the dose density of the agents improves DFS and OS ; and to compare toxicities . PATIENTS AND METHODS A total of 2,005 female patients were r and omly assigned to receive one of the following regimens : ( I ) sequential A x 4 ( doses ) -- > T x 4 -- > C x 4 with doses every 3 weeks , ( II ) sequential A x 4 -- > T x 4 -- > C x 4 every 2 weeks with filgrastim , ( III ) concurrent AC x 4 -- > T x 4 every 3 weeks , or ( IV ) concurrent AC x 4 -- > T x 4 every 2 weeks with filgrastim . RESULTS A protocol -specified analysis was performed at a median follow-up of 36 months : 315 patients had experienced relapse or died , compared with 515 expected treatment failures . Dose-dense treatment improved the primary end point , DFS ( risk ratio [ RR ] = 0.74 ; P = .010 ) , and OS ( RR = 0.69 ; P = .013 ) . Four-year DFS was 82 % for the dose-dense regimens and 75 % for the others . There was no difference in either DFS or OS between the concurrent and sequential schedules . There was no interaction between density and sequence . Severe neutropenia was less frequent in patients who received the dose-dense regimens . CONCLUSION Dose density improves clinical outcomes significantly , despite the lower than expected number of events at this time . Sequential chemotherapy is as effective as concurrent chemotherapy BACKGROUND The purpose of this study was to evaluate the impact of a dose-dense primary chemotherapy on pathological response rate ( pCR ) in patients with locally advanced breast cancer ( LABC ) treated with combined modality therapy . PATIENTS AND METHODS Stage IIIA/IIIB patients received three courses of induction chemotherapy ( ICT ) with cyclophosphamide , epirubicin and 5-fluorouracil ( CEF ) followed by local therapy ( total mastectomy or segmental mastectomy with axillary nodes dissection ) and adjuvant chemotherapy ( ACT ) with three courses of CEF alternated with three courses of cyclophosphamide , methotrexate , 5-fluorouracil ( CMF ) . Patients were r and omized to receive ICT and ACT every 3 weeks ( arm A , ' st and ard treatment ' ) or every 2 weeks with granulocyte-macrophage colony-stimulating factor ( GM-CSF ) support ( arm B , ' dose-dense treatment ' ) . In both arms radiotherapy was administered after the end of chemotherapy ( in selected cases ) and patients with hormonal receptor-positive tumors received tamoxifen for 5 years . RESULTS A total of 150 patients were r and omized ( 77 arm A and 73 arm B ) and demographics were well balanced between the two arms . Compliance to treatment was excellent : 95 % and 93 % of patients in arms A and B , respectively , completed the treatment program with no modification or delay . Median duration of treatment ( ICT+local+ACT ) was 183 days ( range 0 - 265 ) in arm A and 139 days ( 0 - 226 ) in arm B. The average relative dose intensity ( ARDI ) of chemotherapy was 1.3 with a 30 % increase in the dose intensity in arm B in comparison with arm A. No difference in clinical [ 62 % ; 95 % confidence interval ( CI ) 49 % to 73.2 % ] and pathological response rates to ICT was observed between the two arms . Median follow-up was 5 years ( range 1 - 96 months ) ; median disease-free survivals were 4.8 years in arm A and 4.5 years in arm B. Median overall survival was 7.8 years in st and ard therapy : this figure has not yet been reached in the dose-dense treatment . CONCLUSIONS In LABC a dose-dense regimen , while allowing a 30 % increase in the dose intensity of chemotherapy , did not provide significant improvement in pathological response rates . However , accelerated chemotherapy reduced the duration of the combined-modality program ( 6.1 versus 4.6 months ) with no additional toxicities The pattern of growth of human breast cancer is important theoretically and clinical ly . Speer et al. ( Cancer Res . , 44 : 4124 - 4130 , 1984 ) have recently proposed that all individual tumors initially grow with identical Gompertzian parameters , but subsequently develop kinetic heterogeneity by a r and om time-dependent process . This concept has elicited interest because it fits clinical data for the survival of untreated patients , for the progression of shadows on serial paired mammograms , and for time-to-relapse following mastectomy . The success of these curve-fits is compelling , and the model has been applied to clinical trials . However , the assumption of uniform nascent growth is not supported by theory or data , and individual cancers have not been shown to follow the complex growth curves predicted by the Speer model . As an alternative , if kinetic heterogeneity is understood to be an intrinsic property of neoplasia , the same three historical data sets are fit well by an unadorned Gompertzian model which is parsimonious and has many other intuitive and empirical advantages . The two models differ significantly in such clinical projections as the estimated duration of silent growth prior to diagnosis and the anticipated optimal chemotherapy schedule postsurgery BACKGROUND AND OBJECTIVES Treatment with CHOP chemotherapy in elderly patients with aggressive non-Hodgkin 's lymphoma ( NHL ) is less effective and accompanied by more adverse effects than in younger patients . The prophylactic use of granulocyte colony-stimulating factor ( G-CSF ) might improve the results , but increases the costs of treatment . We analyzed the costs of therapy and follow-up of patients with NHL treated with CHOP with or without G-CSF prophylaxis . DESIGN AND METHODS Four hundred and eleven patients were r and omized for treatment with CHOP or CHOP+G-CSF . A detailed study of treatment costs from r and omization until 3 years of follow-up or death was performed in a subset of 100 out of 389 eligible patients . Because costs during follow-up were independent of the use of G-CSF during treatment , costs of follow-up and second-line treatment were calculated irrespective of the treatment arm . RESULTS Total hospital costs for first-line treatment were 12178 [ 95 % CI 10297 - 14059 ] for CHOP alone and 18356 [ 95 % CI 15807 - 20906 ] for CHOP + G-CSF . Costs during follow-up showed a wide difference ( range 74 - 53925 ) depending on disease status and choice of treatment in the case of relapse or progression . INTERPRETATION AND CONCLUSIONS The clinical study showed no difference between the treatment arms in response , overall survival or event-free survival , while the costs were significantly higher in the G-CSF arm . We conclude that the addition of prophylactic G-CSF to CHOP chemotherapy is not cost-effective in these patients 513 Background : Dose-dense chemotherapy will become a new treatment option in breast cancer patients ( pts ) ( INT C9741 ) . Here we report the initial results of a second prospect i ve r and omized trial that compares dose-dense vs. conventionally scheduled sequential chemotherapy in high-risk node positive pts . METHODS A multi-center phase-III trial of the German " Arbeitsgemeinschaft fuer Gynaekologische Onkologie ( AGO ) " recruited 1284 pts from 12/98 until 4/03 . Pts below 65 years of age were eligible if they had at least 4 involved axillary lymph nodes . In the experimental arm , pts were assigned to receive three courses each of epirubicin(150 mg/m2 ) , paclitaxel ( 225 mg/m2 ) and cyclophosphamide ( 2500 mg/m2 ) at 2 weeks interval ( q2wks ) ( ETC ) with G-CSF support ( 5μg/kg/SC day 3 - 10 ) . A second r and omization ± Epoetin-alpha was performed ( 150 IU/kg/SC three times weekly ) . In the st and ard arm 4 courses of conventional dosed epirubicin/cyclophosphamide ( 90/600 mg/m2 ) followed by 4 courses of paclitaxel ( 175 mg/m2 ) ( q3wks ) were given . RESULTS Median patient age was 50 years . Risk factors were well balanced in both arms . 59 % and 41 % of the pts had 4 - 9 and ≥10 infiltrated nodes . The median number of positive nodes was 8 . In this second interim analysis 1169 pts were fully evaluable . No unusual toxicities were seen , especially no severe cardiotoxicity . Hematological toxicity ( anemia , neutropenia and thrombopenia ) was more frequent in the ETC arm ( p<0,0001 ) and varied distinctly between drugs . The incidence was highest during treatment with cyclophosphamide and lowest during treatment with paclitaxel . 7 % of pts in the ETC arm vs. 2 % in the st and ard arm were hospitalized for febrile neutropenia ( p<0,0001 ) . There were no treatment-related deaths during therapy . 82 % of pts in the ETC arm vs. 90 % in the st and ard arm received the planned number of cycles . The number of dose reductions was relatively small , ranging from 6,5 % on the ETC arm to 2 % on the st and ard arm . At a median follow-up of 28 months 94 pts in the ETC arm vs. 127 pts in the st and ard arm had relapsed . This difference was highly significant in the two-sided log-rank test ( p=0,0009 ) with a HR of 0,64 ( 95 % CI : 0,49 - 0,83 ) . Estimated 3-year RFS is 80 % in the ETC arm vs. 70 % in the st and ard arm . 103 pts have died ( 43 events vs. 60 events ) favoring again the ETC arm ( two-sided log-rank test : p=0,030 ; HR : 0,65 ( 95 % CI : 0,44 - 0,96 ) . Estimated 3-year OAS is 90 % in the ETC arm vs. 87 % in the st and ard arm . There was a highly significant difference in anemia grade 1 - 4 as well as in the number of RBC 's transfusions between ETC ± Epoetin alpha ( p<0,0001 ) . No difference in DFS ( p=0,84 ) or OAS ( p=0,98 ) was found between ETC ± Epoetin alpha . CONCLUSIONS Evidence to date indicates that the dose-dense ETC-regimen as adjuvant therapy in high-risk breast cancer pts is well tolerated and significantly improves DFS and OAS . Confirming the results of INT C9741 , dose-dense sequential regimens may become a future st and ard option in the adjuvant treatment of node positive breast cancer pts . [ Table : see text ] PURPOSE Dose-dense chemotherapy is predicted to be a superior treatment plan . Therefore , we studied dose-dense doxorubicin , paclitaxel , and cyclophosphamide ( A-->T-->C ) as adjuvant therapy . METHODS Patients with resected breast cancer involving four or more ipsilateral axillary lymph nodes were treated with nine cycles of chemotherapy , using 14-day intertreatment intervals . Doses were as follows : doxorubicin 90 mg/m2 x 3 , then paclitaxel 250 mg/m2/24 hours x 3 , and then cyclophosphamide 3.0 g/m2 x 3 ; all doses were given with subcutaneous injections of 5 microg/kg granulocyte colony-stimulating factor on days 3 through 10 . Amenorrheic patients with hormone receptor-positive tumors received tamoxifen 20 mg/day for 5 years . Patients treated with breast conservation , those with 10 or more positive nodes , and those with tumors larger than 5 cm received radiotherapy . RESULTS Between March 1993 and June 1994 , we enrolled 42 patients . The median age was 46 years ( range , 29 to 63 years ) , the median number of positive lymph nodes was eight ( range , four to 25 ) , and the median tumor size was 3.0 cm ( range , 0 to 11.0 cm ) . The median intertreatment interval was 14 days ( range , 13 to 36 days ) , and the median delivered dose-intensity exceeded 92 % of the planned dose-intensity for all three drugs . Hospital admission was required for 29 patients ( 69 % ) , and 28 patients ( 67 % ) required blood product transfusion . No treatment-related deaths or cardiac toxicities occurred . Doxorubicin was dose-reduced in four patients ( 10 % ) and paclitaxel was reduced in eight ( 20 % ) . At a median follow-up from surgery of 48 months ( range , 3 to 57 months ) , nine patients ( 19 % ) had relapsed , the actuarial disease-free survival rate was 78 % ( 95 % confidence interval , 66 % to 92 % ) , and four patients ( 10 % ) had died of metastatic disease . CONCLUSION Dose-dense sequential adjuvant chemotherapy with doxorubicin , paclitaxel , and cyclophosphamide ( A-->T-->C ) is feasible and promising . Several ongoing phase III trials are evaluating this approach BACKGROUND Prompted by complaints of dyspnea in breast cancer patients receiving adjuvant dose-dense chemotherapy ( DDC ) , we sought to evaluate the possible association of DDC with pulmonary dysfunction . PATIENTS AND METHODS A total of 34 consecutive patients receiving adjuvant DDC were enrolled . The chemotherapy regimen consisted of i.v . doxorubicin 60 mg/m(2 ) and cyclophosphamide 600 mg/m(2 ) ( AC ) every 14 days x4 with growth factor support followed by weekly i.v . paclitaxel 80 mg/m(2 ) x12 . The following parameters were prospect ively measured before and after the AC protocol ( P1 , P2 ) and at completion of paclitaxel treatment ( P3 ) : presence of dyspnea , blood pressure , pulse rate , hemoglobin , erythrocyte sedimentation rate , C-reactive protein level , cardiac ejection fraction , and pulmonary function . Repeated measures analysis was used to evaluate differences among the time points , and paired t-test was used to evaluate differences between consecutive time points . RESULTS Although only five patients ( 15 % ) complained of dyspnea , there was a significant decrease in mean carbon monoxide diffusing capacity ( DLCO ) , in all patients from P1 ( 22.09 ml/min/mmHg ) to P3 ( 15 ml/min/mmHg ) and in 29 of 32 patients ( 90.6 % ) from P1 to P2 ( 15.96 ml/min/mmHg ) ( P<0.001 ) . CONCLUSIONS DDC is associated with a statistical significant reduction in DLCO . Awareness of this potential toxicity may be important in women with preexisting lung disease PURPOSE Dose-dense and sequential administration of cytotoxic drugs are current approaches to improve outcomes in patients with early-stage breast cancer . METHODS This phase III study investigated 913 women with untreated operable breast cancer ( T2 - 3 , N0 - 2 , M0 ) r and omly assigned to receive either doxorubicin 50 mg/m2 plus docetaxel 75 mg/m2 every 14 days for four cycles with filgrastim support ( ADOC ) , or doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 every 21 days followed by docetaxel 100 mg/m2 every 21 days for four cycles each ( AC-DOC ) . The primary end point was the incidence of pathologic complete ( invasive and noninvasive ) response ( pCR ) in the breast and axillary nodes . Secondary end points were predictors for pCR , clinical response , rate of breast conservation , and safety . RESULTS A pCR was achieved in 94 patients ( 10.6 % ) , but the likelihood was significantly greater with AC-DOC ( 14.3 % ; n = 63 ) than with ADOC ( 7.0 % ; n = 31 ) ( odds ratio , 2.22 ; 90 % CI , 1.52 to 3.24 ; P < .001 ) . Independent predictors of attaining a pCR included the use of sequential therapy , high tumor grade , and negative hormone receptor status . The response rates detected by palpation and by imaging were significantly higher with AC-DOC ( 85.0 % and 78.6 % , respectively ) than with ADOC ( 75.2 % and 68.6 % , respectively ; both P values < .001 ) . The rate of breast-conserving surgery was 63.4 % for AC-DOC and 58.1 % for ADOC ( P = .05 ) . Predominant grade 3/4 toxicities were leucopenia ( AC-DOC , 74.2 % ; ADOC , 53.7 % ) and neutropenia ( AC-DOC , 66.4 % ; ADOC , 44.7 % ) but were infrequently associated with fever ( AC-DOC , 4.6 % ; ADOC , 3.1 % ) . CONCLUSION Sequential AC-DOC is more effective at inducing pCR than dose-dense ADOC as preoperative treatment for patients with operable breast cancer PURPOSE We conducted a phase III r and omized study of two adjuvant treatment schedules of doxorubicin ( A ) and cyclophosphamide ( C ) in early-stage breast cancer to determine if administration of sequential single agents ( A -- > C ) results in superior disease-free survival ( DFS ) and overall survival ( OS ) versus the same total dose given in combination ( AC ) . PATIENTS AND METHODS High-risk node-negative or low-risk node-positive breast cancer patients received AC given : ( arm I ) concurrently ( AC ) doxorubicin 54 mg/m2 and cyclophosphamide 1.2 g/m2 intravenously ( IV ) every 3 weeks for six cycles ; or ( arm II ) in sequence ( A C ) doxorubicin 40.5 mg/m2 IV days 1 and 2 every 3 weeks for four cycles followed by cyclophosphamide 2.4 gm/m2 IV every 2 weeks for three cycles . Total dose and duration were identical , but the intensity of each drug was increased on A C. Both arms included granulocyte colony-stimulating factor support and prophylactic antibiotics . All but premenopausal women with receptor negative tumors received tamoxifen after chemotherapy . RESULTS Between 1994 and 1997 , 3,176 patients were r and omly assigned . Arms were well balanced ; 48 % of eligible patients were node-negative and 48 % were estrogen receptor-positive . No significant differences in OS or DFS were observed ; 5-year estimates of OS ( 95 % CI ) were 88 % ( 87 % to 90 % ) on AC and 89 % ( 87 % to 91 % ) on A -- > C. Grade 4 hematologic toxicity was greater on A -- > C , but nonhematological grade 4 was similar . CONCLUSION The overall result does not support superiority of dose-intense sequenced single agents . The greater toxicity of higher doses of single agents does not support their sequential use PURPOSE Recently , a Dutch , r and omized , phase III trial demonstrated that , in small-cell lung cancer patients at risk of chemotherapy-induced febrile neutropenia ( FN ) , the addition of granulocyte colony-stimulating factor ( GCSF ) to prophylactic antibiotics significantly reduced the incidence of FN in cycle 1 ( 24 % v 10 % ; P = .01 ) . We hypothesized that selecting patients at risk of FN might increase the cost-effectiveness of GCSF prophylaxis . METHODS Economic analysis was conducted alongside the clinical trial and was focused on the health care perspective . Primary outcome was the difference in mean total costs per patient in cycle 1 between both prophylactic strategies . Cost-effectiveness was expressed as costs per percent-FN-prevented . RESULTS For the first cycle , the mean incremental costs of adding GCSF amounted to 681 euro ( 95 % CI , -36 to 1,397 euro ) per patient . For the entire treatment period , the mean incremental costs were substantial ( 5,123 euro ; 95 % CI , 3,908 to 6,337 euro ) , despite a significant reduction in the incidence of FN and related savings in medical care consumption . The incremental cost-effectiveness ratio was 50 euro per percent decrease of the probability of FN ( 95 % CI , -2 to 433 euro ) in cycle 1 , and the acceptability for this willingness to pay was approximately 50 % . CONCLUSION Despite the selection of patients at risk of FN , the addition of GCSF to primary antibiotic prophylaxis did not result in cost savings . If policy makers are willing to pay 240 euro for each percent gain in effect ( ie , 3,360 euro for a 14 % reduction in FN ) , the addition of GCSF can be considered cost effective PURPOSE Cyclophosphamide , epirubicin , and fluorouracil ( CEF ) and doxorubicin and cyclophosphamide ( AC ) followed by paclitaxel ( T ) are commonly used adjuvant regimens in women with early breast cancer . In a previous trial in women with locally advanced breast cancer , 3 months of high-dose epirubicin and cyclophosphamide ( EC ) administered every 2 weeks ( dose-dense ) was equivalent to 6 months of CEF . We hypothesized that 3 months of paclitaxel after dose-dense EC ( EC/T ) would be superior to CEF or AC/T. METHODS After lumpectomy or mastectomy , women 60 years of age or younger with axillary node-positive or high-risk node-negative breast cancer were r and omly assigned to receive CEF , EC/T , or AC/T for 6 months . This article reports the interim analysis for recurrence-free survival ( RFS ) , which was planned after 227 recurrences . Results A total of 2,104 patients were enrolled . The median follow-up is 30.4 months . Hazard ratios for recurrence are as follows : AC/T versus CEF , 1.49 ( 95 % CI , 1.12 to 1.99 ) , P = .005 ; AC/T versus EC/T , 1.68 ( 95 % CI , 1.25 to 2.27 ) , P = .0006 ; and EC/T versus CEF , 0.89 ( 95 % CI , 0.64 to 1.22 ) , P = .46 . Three-year RFS rates for CEF , EC/T , and AC/T are 90.1 % , 89.5 % , and 85.0 % , respectively . There was more febrile neutropenia with CEF ( 22.3 % ) and EC/T ( 16.4 % ) compared with AC/T ( 4.8 % ) , but more neuropathy with the last two regimens . CONCLUSION Three-weekly AC/T is significantly inferior to CEF or EC/T in terms of RFS . It is too early to detect any difference between CEF and dose-dense PURPOSE To compare preoperative intense dose-dense ( IDD ) chemotherapy with conventionally scheduled preoperative chemotherapy in high-risk primary breast cancer ( BC ) . PATIENTS AND METHODS In this r and omized phase III trial a total of 668 eligible primary BC patients stratified for tumors > or = 3 cm ( n = 567 ) or inflammatory BC ( n = 101 ) were r and omly assigned to receive concurrent preoperative epirubicin/paclitaxel every 3 weeks or dose-dense and dose-escalated sequential epirubicin followed by paclitaxel every 2 weeks . All patients received three cycles of cyclophosphamide , methotrexate , and fluorouracil chemotherapy after surgery . RESULTS IDD treatment significantly improved pathologic complete response rate ( 18 % v 10 % ; odds ratio [ OR ] 1.89 ; P = .008 ) , disease-free survival ( DFS ; hazard ratio [ HR ] , 0.71 ; P = .011 ) , and overall survival ( OS ; HR , 0.83 ; P = .041 ) compared to epirubicin/paclitaxel . Patients with inflammatory BC had a particularly poor prognosis and did not appear to benefit from IDD therapy in this trial ( DFS HR , 1.10 ; P = .739 ; OS HR , 1.25 ; P = .544 ) . In contrast , patients with noninflammatory BC significantly benefited from IDD treatment ( DFS HR , 0.65 , P = .005 ; OS HR , 0.77 , P = .013 ) . Treatment effects in multivariate analysis were significant for noninflammatory BC ( DFS HR , 0.65 , P = .015 ; OS HR , 0.79 , P = .034 ) , but not for all patients ( DFS HR , 0.76 ; P = .088 ; OS HR , 0.82 ; P = .059 ) . IDD therapy was associated with significantly more nonhematologic toxicities , anemia , and thrombocytopenia , but with similar neutropenia and infection rates . CONCLUSION Our results support the efficacy and short-term safety of IDD as preoperative chemotherapy . IDD was less well tolerated compared to st and ard treatment , but improved clinical outcomes in patients with noninflammatory high-risk primary BC |
12,945 | 28,822,116 | Almost consistently , these studies revealed that polymorphisms in COMT , BDNF , and FKBP5 genes might interact with early life stress and cannabis abuse or dependence , influencing various outcomes of schizophrenia spectrum disorders and BD . | Schizophrenia and bipolar disorder ( BD ) are complex and multidimensional disorders with high heritability rates .
The contribution of genetic factors to the etiology of these disorders is increasingly being recognized as the action of multiple risk variants with small effect sizes , which might explain only a minor part of susceptibility .
On the other site , numerous environmental factors have been found to play an important role in their causality .
Therefore , in recent years , several studies focused on gene × environment interactions that are believed to bridge the gap between genetic underpinnings and environmental insults .
In this article , we performed a systematic review of studies investigating gene × environment interactions in BD and schizophrenia spectrum phenotypes .
In the majority of studies from this field , interacting effects of variation in genes encoding catechol-O-methyltransferase ( COMT ) , brain-derived neurotrophic factor ( BDNF ) , and FK506-binding protein 5 ( FKBP5 ) have been explored . | OBJECTIVE Using longitudinal and prospect i ve measures of trauma during childhood , the authors assessed the risk of developing psychotic symptoms associated with maltreatment , bullying , and accidents in a nationally representative U.K. cohort of young twins . METHOD Data were from the Environmental Risk Longitudinal Twin Study , which follows 2,232 twin children and their families . Mothers were interviewed during home visits when children were ages 5 , 7 , 10 , and 12 on whether the children had experienced maltreatment by an adult , bullying by peers , or involvement in an accident . At age 12 , children were asked about bullying experiences and psychotic symptoms . Children 's reports of psychotic symptoms were verified by clinicians . RESULTS Children who experienced mal-treatment by an adult ( relative risk=3.16 , 95 % CI=1.92 - 5.19 ) or bullying by peers ( relative risk=2.47 , 95 % CI=1.74 - 3.52 ) were more likely to report psychotic symptoms at age 12 than were children who did not experience such traumatic events . The higher risk for psychotic symptoms was observed whether these events occurred early in life or later in childhood . The risk associated with childhood trauma remained significant in analyses controlling for children 's gender , socioeconomic deprivation , and IQ ; for children 's early symptoms of internalizing or externalizing problems ; and for children 's genetic liability to developing psychosis . In contrast , the risk associated with accidents was small ( relative risk=1.47 , 95 % CI=1.02 - 2.13 ) and inconsistent across ages . CONCLUSIONS Trauma characterized by intention to harm is associated with children 's reports of psychotic symptoms . Clinicians working with children who report early symptoms of psychosis should inquire about traumatic events such as maltreatment and bullying BACKGROUND Victims of bullying are at risk for psychotic experiences in early adolescence . It is unclear if this elevated risk extends into late adolescence . The aim of this study was to test whether bullying perpetration and victimization in elementary school predict psychotic experiences in late adolescence . METHOD The current study is based on the Avon Longitudinal Study of Parents and Children ( ALSPAC ) , a prospect i ve community-based study . A total of 4720 subjects with bullying perpetration and victimization were repeatedly assessed between the ages of 8 and 11 years by child and mother reports . Suspected or definite psychotic experiences were assessed with the Psychosis-Like Symptoms semi-structured interview at age 18 years . RESULTS Controlling for child 's gender , intelligence quotient at age 8 years , childhood behavioural and emotional problems , and also depression symptoms and psychotic experiences in early adolescence , victims [ child report at 10 years : odds ratio ( OR ) 2.4 , 95 % confidence interval ( CI ) 1.6 - 3.4 ; mother report : OR 1.6 , 95 % CI 1.1 - 2.3 ] , bully/victims ( child report at 10 years : OR 3.1 , 95 % CI 1.7 - 5.8 ; mother : OR 2.9 , 95 % CI 1.7 - 5.0 ) and bullies ( child report at 10 years : OR 4.9 , 95 % CI 1.3 - 17.7 ; mother : OR 1.2 , 95 % CI 0.46 - 3.1 , n.s . ) had a higher prevalence of psychotic experiences at age 18 years . Path analysis revealed that the association between peer victimization in childhood and psychotic experiences at age 18 years was only partially mediated by psychotic or depression symptoms in early adolescence . CONCLUSIONS Involvement in bullying , whether as victim , bully/victim or bully , may increase the risk of developing psychotic experiences in adolescence . Health professionals should ask routinely during consultations with children about their bullying of and by peers Observational studies have suggested that psychometric psychosis liability and a functional polymorphism in the catechol-O-methyltransferase ( COMT Val158Met ) gene moderate the psychosis-inducing effect of cannabis . To replicate and extend this finding , a double-blind , placebo-controlled cross-over design was used in which patients with a psychotic disorder ( n=30 ) , relatives of patients with a psychotic disorder ( n=12 ) , and healthy controls ( n=32 ) were exposed to Δ-9-tetrahydrocannabinol ( Δ-9-THC , the principal component of cannabis ) or placebo , followed by cognitive assessment and assessment of current psychotic experiences . Previous expression of psychometric psychosis liability was also assessed . Models of current psychotic experiences and cognition were examined with multilevel r and om regression analyses to assess ( i ) main effects of genotype and condition , ( ii ) interactions between condition and genotype , and ( iii ) three-way interactions between condition , genotype , and psychometric psychosis liability . Carriers of the Val allele were most sensitive to Δ-9-THC-induced psychotic experiences , but this was conditional on prior evidence of psychometric psychosis liability . Δ-9-THC impacted negatively on cognitive measures . Carriers of the Val allele were also more sensitive to Δ-9-THC-induced memory and attention impairments compared to carriers of the Met allele . Experimental effects of Δ-9-THC on cognition and psychosis are moderated by COMT Val158Met genotype , but the effects may in part be conditional on the additional presence of pre-existing psychosis liability . The association between cannabis and psychosis may represent higher order gene – environment and gene – gene interactions Positive and negative schizotypy exhibit differential patterns of impairment in social relations , affect , and functioning in daily life . However , studies have not examined the association of schizotypy with real-world expression of psychotic-like , paranoid , and negative symptoms . The present study employed experience-sampling methodology ( ESM ) to assess positive and negative schizotypy in daily life in a non clinical sample of 206 Spanish young adults . Participants were prompted r and omly 8 times daily for 1 week to complete assessment s of their current symptoms and experiences . Positive schizotypy was associated with psychotic-like and paranoid symptoms in daily life . Negative schizotypy was associated with a subset of these symptoms and with negative symptoms in daily life . Momentary stress was associated with psychotic-like and paranoid symptoms , but only for those high in positive schizotypy . Social stress predicted momentary psychotic-like symptoms in both positive and negative schizotypy . Time-lagged analyses indicated that stress at the preceding signal predicted psychotic-like symptoms at the current assessment , but only for individuals high in positive schizotypy . The results are consistent with models linking stress sensitivity with the experience of psychotic symptoms . The findings provide cross-cultural support for the multidimensional model of schizotypy and schizophrenia . Furthermore , the findings demonstrate that ESM is an effective method for predicting the experience of psychotic-like symptoms , as well as their precursors , in daily life OBJECTIVE Many studies have implicated prenatal infection in the etiology of schizophrenia . Cytokines , a family of soluble polypeptides , are critically important in the immune response to infection and in other inflammatory processes . The goal of this study was to determine whether second-trimester levels of four cytokines-interleukin-8 ( IL-8 ) , interleukin-1beta ( IL-1beta ) , interleukin-6 ( IL-6 ) , and tumor necrosis factor-alpha (TNF-alpha)-are higher in the mothers of offspring who later developed schizophrenia spectrum disorders than in matched comparison subjects . METHOD The authors conducted a nested case-control study of maternal serum cytokine levels in a large birth cohort , born 1959 - 1967 . Cases ( N=59 ) were subjects diagnosed with schizophrenia spectrum disorders ( mostly schizophrenia and schizoaffective disorder ) who had available second-trimester maternal serum sample s. Comparison subjects ( N=105 ) were members of the birth cohort , had not been diagnosed with a schizophrenia spectrum disorder or major affective disorder , and were matched to subjects with schizophrenia for date of birth , gender , length of time in the cohort , and availability of maternal sera . Maternal second-trimester serum levels of IL-8 , IL-1beta , IL-6 , and TNF-alpha were determined by s and wich enzyme-linked immunosorbent assay . RESULTS The second-trimester IL-8 levels in mothers of offspring with schizophrenia spectrum disorders were significantly higher than those of the mothers of comparison subjects . There were no differences between subjects with schizophrenia and comparison subjects with respect to maternal levels of IL-1beta , IL-6 , or TNF-alpha . CONCLUSIONS Using prospect ively collected prenatal sera in a large and well-characterized birth cohort , the authors have documented a significant association between maternal IL-8 level during the second trimester and risk of schizophrenia spectrum disorders in the offspring . These findings provide further support for a substantive role of in utero infection or inflammation in the etiology of schizophrenia . Moreover , these results may have important implication s for elucidating the mechanisms by which disrupted fetal development raises the risk of this disorder This article reports on the development and reliability of the Diagnostic Interview for Genetic Studies ( DIGS ) , a clinical interview especially constructed for the assessment of major mood and psychotic disorders and their spectrum conditions . The DIGS , which was developed and piloted as a collaborative effort of investigators from sites in the National Institute of Mental Health ( NIMH ) Genetics Initiative , has the following additional features : ( 1 ) polydiagnostic capacity ; ( 2 ) a detailed assessment of the course of the illness , chronology of psychotic and mood syndromes , and comorbidity ; ( 3 ) additional phenomenologic assessment s of symptoms ; and ( 4 ) algorithmic scoring capability . The DIGS is design ed to be employed by interviewers who exercise significant clinical judgment and who summarize information in narrative form as well as in ratings . A two-phase test-retest ( within-site , between-site ) reliability study was carried out for DSM-III-R criteria -based major depression , bipolar disorder , schizophrenia , and schizoaffective disorder . Reliabilities using algorithms were excellent ( 0.73 to 0.95 ) , except for schizoaffective disorder , for which disagreement on estimates of duration of mood syndromes relative to psychosis reduced reliability . A final best-estimate process using medical records and information from relatives as well as algorithmic diagnoses is expected to be more reliable in making these distinctions . The DIGS should be useful as part of archival data gathering for genetic studies of major affective disorders , schizophrenia , and related conditions Aim The present study employed Experience Sampling Methodology to examine whether the interaction between childhood bullying and FKBP5 variability ( i ) is associated with the expression of psychotic-like experiences , paranoia , and negative affect , and ( ii ) moderates psychotic-like , paranoid , and affective reactivity to different forms of momentary stress ( situational and social ) in daily life . Methods A total of 206 non clinical young adults were interviewed for bullying with the Childhood Experience of Care and Abuse and were prompted r and omly eight times daily for one week to complete assessment s of their current experiences , affect , and stress appraisal s. Participants were genotyped for three FKBP5 single nucleotide polymorphisms ( SNPs ) ( rs3800373 , rs9296158 , and rs1360780 ) that have been linked to hypothalamus-pituitary-adrenal axis reactivity . Multilevel analyses were conducted to examine the effect of the interaction between childhood bullying and the FKBP5 haplotype derived from these three SNPs . Results The interaction between bullying and the FKBP5 haplotype was associated with positive , but not negative , psychotic-like experiences , paranoia , and negative affect . The bullying x FKBP5 interaction also moderated the association of a social stress appraisal ( specifically , being alone because people do not want to be with you ) with psychotic-like experiences and negative affect in daily life . Simple slopes analyses indicated that , in all cases , the associations were significantly increased by exposure to bullying in participants with the risk haplotype , but not for those with the non-risk haplotype . Discussion The present study provides the first evidence of the interplay between childhood bullying and FKBP5 variability in the real-world expression of psychosis proneness and social stress reactivity . The findings underscore the importance of investigating how gene-environment interactions are involved in mechanistic pathways to the extended psychosis phenotype and lend further support to the increasing relevance given to socially defeating appraisal s in the experience of reality distortion The Clinical Global Impressions Scale ( CGI ) was modified specifically for use in assessing global illness severity and change in patients with bipolar disorder . Criticisms of the original CGI were addressed by correcting inconsistencies in scaling , identifying time frames for comparison , clarifying definitions of illness severity and change , and separating out assessment of treatment side effects from illness improvement during treatment . A Detailed User 's Guide was developed to train clinicians in the use of the new CGI-Bipolar Version ( CGI-BP ) for rating severity of manic and depressive episodes and the degree of change from the immediately preceding phase and from the worst phase of illness . The revised scale and manual provide a focused set of instructions to facilitate the reliability of these ratings of mania , depression , and overall bipolar illness during treatment of an acute episode or in longer-term illness prophylaxis . Interrater reliability of the scale was demonstrated in preliminary analyses . Thus , the modified CGI-BP is anticipated to be more useful than the original CGI in studies of bipolar disorder Not all individuals who smoke cannabis report psychotic-like experiences . Given that risk factors for psychotic disorders are multifaceted , precipitating factors to psychotic-like experiences after cannabis are likely to be equally complex . Reduced neurocognitive performance is associated with both psychosis risk and cannabis use . Therefore , it is possible cognitive performance may differentiate those who report psychotic-like experiences after cannabis from those who do not . We determined whether those reporting psychotic/dysphoric experiences after cannabis had reduced neurocognitive performance compared to those reporting primarily euphoric experiences . METHODS Participants were recruited on the basis of responses to the cannabis high captured by the Psychosis-Dysphoric and Euphoric experiences subscales from the Cannabis Experiences Question naire ( CEQ ) . RESULTS Compared to participants reporting primarily euphoric cannabis experiences ( n = 36 ; 44 % male ; mean age ( SD ) = 28 ( 9 ) years ) , those who reported psychotic/dysphoric experiences ( n = 40 ; 45 % male ; mean age ( SD ) = 26 ( 5 ) years ) demonstrated significantly faster responses to a trial and error learning task . In the presence of distracters , those with psychotic/dysphoric experiences after cannabis made more errors on a Continuous Performance Task . CONCLUSIONS Those who report psychotic/dysphoric experiences after cannabis have subtle inefficiencies in their cognitive processes . The multiple factors which predict vulnerability to psychotic-like experiences after cannabis require further investigation BACKGROUND Influential studies have cast doubt on the validity of retrospective reports by adults of their own adverse experiences in childhood . Accordingly , many research ers view retrospective reports with scepticism . METHOD A computer-based search , supplemented by h and search es , was used to identify studies reported between 1980 and 2001 in which there was a quantified assessment of the validity of retrospective recall of sexual abuse , physical abuse , physical/emotional neglect or family discord , using sample s of at least 40 . Validity was assessed by means of comparisons with contemporaneous , prospect ively obtained , court or clinic or research records ; by agreement between retrospective reports of two siblings ; and by the examination of possible bias with respect to differences between retrospective and prospect i ve reports in their correlates and consequences . Medium- to long-term reliability of retrospective recall was determined from studies in which the test-retest period extended over at least 6 months . RESULTS Retrospective reports in adulthood of major adverse experiences in childhood , even when these are of a kind that allow reasonable operationalisation , involve a substantial rate of false negatives , and substantial measurement error . On the other h and , although less easily quantified , false positive reports are probably rare . Several studies have shown some bias in retrospective reports . However , such bias is not sufficiently great to invali date retrospective case-control studies of major adversities of an easily defined kind . Nevertheless , the findings suggest that little weight can be placed on the retrospective reports of details of early experiences or on reports of experiences that rely heavily onjudgement or interpretation . CONCLUSION Retrospective studies have a worthwhile place in research , but further research is needed to examine possible biases in reporting In a survey of a r and om sample of the general population recent life events , collected and rated for long-term context ual threat according to the methods of Brown & Harris ( 1978 ) , were also recorded where possible on an inventory of life event categories ( Tennant & And rews , 1977 ) . Of the 82.5 % of all events collected which were covered by the inventory , 12 of the 67 event categories accounted for 77 % of life events with an aetiologicaly significant rating of marked or moderate long-term threat . Where practical and economic constraints oblige research workers to choose the inventory method , a brief list of event categories , such as the List of Threatening Experiences , is recommended in preference to much longer lists Neuropsychological assessment of older individuals with dementing illnesses has suffered from a lack of appropriately design ed test instruments . The Repeatable Battery for the Assessment of Neuropsychological Status ( RBANS ) was developed for the dual purpose s of identifying and characterizing abnormal cognitive decline in the older adult and as a neuropsychological screening battery for younger patients . The entire battery takes less than 30 minutes to administer , and yields scaled scores for five cognitive domains . The current study reports preliminary clinical validity results with the RBANS , comparing very mildly demented patients with a diagnosis of probable Alzheimer 's disease ( n = 20 ) to patients with Huntington 's disease ( n = 20 ) and normal controls ( n = 40 ) . Although the patient groups had essentially identical total scores on the RBANS , they exhibited opposite profiles , differing significantly on four of the five subsections . The AD patients performed most poorly on Language , and Delayed Memory subsections , while the HD patients obtained their lowest scaled scores on the Attention and the Visuospatial/Constructional subsections . These results are consistent with the neuropsychological profiles of these dementing disorders derived from lengthier st and ardized tests and experimental investigations . In addition , even those patients who performed above the suggested cut-off points on the MMSE and the Dementia Rating Scale scored significantly below their controls on the RBANS . These data suggest that the RBANS is effective at both detecting and characterizing dementia of different etiologies |
12,946 | 29,376,896 | Conclusions : Topical antifungal medications are the first-line treatment for PV , including zinc pyrithione , ketoconazole , and terbinafine .
In cases of severe or recalcitrant PV , the oral antifungal medications itraconazole and fluconazole may be more appropriate , with pramiconazole a possible future option .
Maintenance , or prophylactic , therapy may be useful in preventing recurrent infection ; however , at this time , there is limited research evaluating the efficacy of prophylactic antifungal treatment | Background : Pityriasis versicolor ( PV ) , also known as tinea versicolor , is caused by Malassezia species .
This condition is one of the most common superficial fungal infections worldwide , particularly in tropical climates .
PV is difficult to cure and the chances for relapse or recurrent infections are high due to the presence of Malassezia in the normal skin flora .
This review focuses on the clinical evidence supporting the efficacy of antifungal treatment for PV . | Flutrimazole is an imidazole derivative that has been proven to be efficient in superficial skin fungal infections . The aim of this r and omised double-blind study was to compare for the first time , the efficiency and safety of flutrimazole 1 % shampoo versus ketoconazole 2 % shampoo in the treatment of tinea versicolor . Study population consisted of 60 patients with pityriasis versicolor diagnosed clinical ly and through direct microscopy and culture . Patients were r and omly assigned to two groups : one instructed to apply flutrimazole shampoo 1 % and one instructed to apply ketoconazole shampoo 2 % both on head and body for 14 days . Patients were re-evaluated 14 days after the end of treatment clinical ly and through direct microscopy and culture . Twenty-one of 26 patients ( 80.8 % ) in the ketoconazole and 22 of 29 patients ( 75.9 % ) in the flutrimazole group had both visual healing and negative mycological evaluation . Comparison of the response between the two groups with the Yates ' corrected chi-square was found statistically not significant ( chi(2 ) = 0.19 , d.f . = 1 , P = 0.91 ) . None of the patients in the two groups reported any adverse effects . Fourteen ( 53 % ) patients in the ketoconazole group and 23 ( 79 % ) in the flutrimazole group assessed the shampoos as cosmetically acceptable regarding texture , smell and foam properties . Flutrimazole shampoo 1 % appears to present efficacy comparable with ketoconazole 2 % in the treatment of tinea versicolor Malassezia furfur ( Pityrosporum orbiculare ) was confirmed by microscopic potassium hydroxide ( KOH ) examination in 101 patients with recurring lesions of tinea versicolor . In a double-blind comparative study , patients were r and omly assigned to once-daily ketoconazole 2 % or placebo cream . At the end of treatment , 98 % ( p less than 0.0001 ) of the patients using ketoconazole and 28 % of those using placebo responded clinical ly ( healed or had mild residual disease ) . There was an overall 84 % mycologic cure rate ( negative KOH at treatment end ) for patients using ketoconazole 2 % cream and 10 % for those using placebo cream ( p less than 0.0001 ) . Ketoconazole-treated patients who were cured at the end of treatment remained cured 8 weeks later . By contrast 75 % of those responding to placebo had relapsed by the 8-week follow-up visit . Follow-up after 2 years revealed that 79 % ( 38/48 ) of the patients treated with ketoconazole remained clear 12 or more months Abstract Background : Ketoconazole cream and adapalene gel are effective drugs against pityriasis versicolor . However , there are no reports on combination treatment with both compounds in pityriasis versicolor . Objective : To evaluate the efficacy and safety of combination therapy with adapalene 0.1 % gel and ketoconazole 2 % cream against pityriasis versicolor . Methods : Participants with pityriasis versicolor were r and omly assigned to two groups : the combination group was treated with adapalene 0.1 % gel and ketoconazole 2 % cream once daily , and the monotherapy group received ketoconazole 2 % cream twice daily . The treatment lasted 2 weeks in both groups . Outcomes were assessed at baseline and 1 , 2 and 4 weeks after the initiation of treatment . Results : We noted clinical ly significant differences in total improvement rates between groups Weeks 1 and 2 . A statistically significant difference was obtained Week 4 . The treatment was well tolerated by all participants . Conclusions : The combination of adapalene 0.1 % gel and ketoconazole 2 % cream is effective and safe in the treatment of pityriasis versicolor . This therapeutic regimen was rapid , providing a valuable option for patients with pityriasis versicolor BACKGROUND Tinea versicolor is a common superficial fungal infection caused by a lipophilic yeast . This chronically recurring opportunistic infection is especially prevalent in tropical and semitropical regions . The topical short-term application of ketoconazole 2 % shampoo may provide effective and safe therapy for tinea versicolor . OBJECTIVE The purpose of this study was to evaluate the efficacy and safety of a single application ( 1 day ) versus three daily applications ( 3 days ) of ketoconazole 2 % shampoo versus placebo shampoo in the treatment of mycologically confirmed tinea versicolor . METHODS Three hundred twelve patients were included in the primary analyses for this 31-day study . Global evaluation scores were measured on days 10 and 31 with a 5-point scale ( 1 = healed to 5 = worsening ) , and a cellophane tape test was done at baseline and days 3 , 10 , and 31 . Efficacy was assessed by clinical response , defined as both a global evaluation score of 1 ( healed ) and a negative cellophane tape test on day 31 . Signs and symptoms of tinea versicolor ( scaling , itching , erythema , hypopigmentation , hyperpigmentation ) also were evaluated at baseline , day 10 , and day 31 with a 4-point scale ( 0 = absent to 3 = severe ) . RESULTS Both regimens of ketoconazole shampoo were significantly ( P < .001 ) more effective than placebo for rate of clinical response , global evaluation scores , and mycologic outcomes ( cellophane tape test ) . The clinical response rates at day 31 were 73 % , 69 % , and 5 % for the 3-day ketoconazole , 1-day ketoconazole , and placebo groups , respectively . The difference in the efficacy of the two ketoconazole treatment regimens was not statistically significant . There were no significant differences between any of the treatment groups in the number of patients who experienced adverse events . No serious adverse events occurred and no patient withdrew from the trial prematurely because of an adverse event . CONCLUSION Ketoconazole 2 % shampoo , used as a single application or daily for 3 days , is safe and highly effective in the treatment of tinea versicolor The antifungal efficacy and tolerability of 1 % terbinafine cream vs. 1 % bifonazole cream were assessed in a single blind r and omized trial in patients with pityriasis versicolor . Terbinafine , a drug of the allylamines group , a new class of anti-mycotic agents , blocks sterol bio synthesis in the pathogen through inhibition of squalene epoxidase and consequent squalene accumulation , a primarily fungicidal process . Forty pityriasis versicolor patients , ( 18 M , 22 F ; mean age 32.4 years ; min . 16 , max . 65 ) , used 1 % terbinafine cream or 1 % bifonazole cream for a maximum of 4 weeks . All patients were followed-up weekly both clinical ly and mycologically . Clinical cures , defined as negativization of each clinical parameter , were recorded for 20 terbinafine patients ( 100 % ) and 19 bifonazole patients ( 95 % ) , with routine microscopy and Wood 's light tests both negative . By the 2nd week of treatment , 2 terbinafine patients were mycologically cured ( 10 % ) . By the 3rd week , 14 terbinafine patients ( 70 % ) and 5 bifonazole patients ( 25 % ) were mycologically cured . The present controlled clinical trial consequently demonstrates that terbinafine is rapidly effective and well tolerated for treatment of pityriasis versicolor An open , comparative trial of two brief regimens of itraconazole for pityriasis versicolor was carried out . Twenty-four patients received 100 mg twice a day for five days , and 23 received 100 mg once a day for five days . Patients were enrolled in the study on the basis of the presence of clinical symptoms and positive findings on direct microscopic examination . Tolerance to the drug and mycologic and clinical outcome were assessed on days 6 , 14 , and 28 after the initiation of treatment . For 23 patients in each group , skin sample s were negative for fungi by day 18 . Clinical improvement was slow ; first scaling disappeared and then erythema and inflammation . Dyschromia persisted during the observation period . Six patients had adverse reactions to treatment ; none discontinued treatment BACKGROUND The use of short-term oral azoles is an alternative to topical therapy in patients with tinea versicolor . OBJECTIVE We compared the efficacy and safety of oral itraconazole with that of placebo in 36 patients with mycologically proven tinea versicolor . METHODS Patients were r and omly assigned to 7 days of treatment with either itraconazole , 200 mg once daily , or placebo . A potassium hydroxide examination and assessment of scaling , erythema , pruritus , and global condition were performed at baseline and at 4 weeks after treatment . RESULTS The itraconazole-treated group demonstrated significant improvement over both baseline ( p < 0.01 ) and placebo ( p < 0.02 ) in scaling , erythema , and pruritus . Sixty-seven percent of itraconazole-treated patients were free of symptoms at week 5 , as compared with 12 % of placebo-treated patients . Ninety-four percent of itraconazole-treated patients were considered to be healed or markedly improved at the study 's end point compared with 6 % of placebo-treated patients ( p < 0.01 ) . A total of 89 % in the itraconazole-treated group had a negative potassium hydroxide examination at the follow-up visit compared with 6 % in the placebo-treated group ( p < 0.01 ) . There was a single report of a possibly treatment-related adverse event in each treatment group . CONCLUSION Short-term treatment with itraconazole is effective and well tolerated in the management of tinea versicolor Two r and omized , double-blind , parallel-group studies , each conducted at five medical centers , assessed the efficacy and safety of a new antifungal agent , ciclopirox olamine cream 1 % , in patients with tinea versicolor . In one study , the antifungal agent was compared with its cream vehicle ; in the other , it was compared with another antifungal compound , 1 % clotrimazole cream . In both studies , treatments were applied twice daily for 14 days . Results with ciclopirox olamine cream were significantly better ( P less than 0.05 ) than those with the vehicle alone after one and two weeks of therapy and at one and two weeks posttherapy . After two weeks of treatment , 49 % of the 73 patients treated with the antifungal cream were clinical ly and mycologically cured , whereas only 24 % of the 72 patients using the vehicle were similarly cured ( P less than 0.001 ) . The clinical cure rate with ciclopirox olamine cream also was significantly better ( P less than 0.05 ) than that with clotrimazole cream . After two weeks of treatment , 77 % of the patients treated with ciclopirox olamine , compared with 45 % of those treated with clotrimazole , had both clinical and mycological cures ( P less than or equal to 0.001 ) . Fourteen days posttreatment , the proportion of patients with a combined response was still greater in the ciclopirox olamine group ( 86 % ) than in the clotrimazole group ( 73 % ) . No side effects were observed in any treatment group Ketomousse ( K ) , a new thermophobic formulation ( ketoconazole 1 % ) , has proven its efficacy in the treatment of d and ruff , caused by the same agent as pityriasis versicolor ( PV ) . The objective of this study was to compare the efficacy and tolerability of K thermophobic foam vs. ketoconazole cream 2 % ( N ) in the treatment of PV . Forty-six patients ( 22 in K and 24 in N group ) with PV involving no more than 15 % of the total trunk surface were r and omly assigned for treatment either with K or N once daily for 14 days . Three weeks after the completion of treatment , improvement rate and side-effects were evaluated by clinical and mycological examination ( Wood 's light ) . Follow-up was available for 81 % of subjects . Complete resolution was observed in five patients ( 29 % ) in K group and in nine ( 47 % ) in N group ( P = 0.291 ) . One patient in the N group reported urticaria while no adverse events were reported for K. Both products were cosmetically acceptable with respect to feasibility of application and formulation with a preference for K. Ketomousse ( 1 % ketoconazole ) provides an equal efficacy and tolerability compared to ketoconazole cream 2 % . Therefore , Ketomousse could be considered an excellent therapeutic option in the treatment of PV BACKGROUND : Tinea ( pityriasis ) versicolor is a superficial infection of the stratum corneum by the lipophilic fungus known as Malassezia furfur . OBJECTIVE : To evaluate the efficacy and safety of a 400 mg single dose or 7-day 200 mg daily dose of itraconazole capsules in the treatment of mycologically confirmed pityriasis versicolor . METHODS : A total of 50 patients were entered into a r and omized , open , clinical trial comparing a 400 mg single dose ( n = 24 for group 1 ) with a 7-day 200 mg daily dose ( n = 26 for group 2 ) of itraconazole . Clinical signs and symptoms and mycologic evaluation ( potassium hydroxide preparation and Wood 's lamp ) were performed before treatment , and at weeks 3 and 6 after treatment . RESULTS : Both regimens of itraconazole were effective . Our results showed that there were no significant differences in efficacy and safety between the two treatment regimens ( chi-square tests , p > 0.05 ) . CONCLUSIONS : On the basis of these findings , a single dose of itraconazole 400 mg/day was as effective as the 7-day 200 mg daily dose in the treatment of pityriasis versicolor A prospect i ve r and omised placebo-controlled double-blind study was design ed to investigate whether topical terbinafine 1 % solution is an effective treatment for subjects with pityriasis versicolor . The intention-to-treat population consisted of 110 subjects . The number of subjects who received terbinafine 1 % solution was 76 and the number who received placebo was 34 ; treatments were given twice a day for 1 week . The primary efficacy variables were categorised at weeks 1 , 2 , 4 and 8 . Eight weeks after the start of therapy , 81 % of the subjects using terbinafine solution and 41 % of those receiving placebo had a negative mycological examination ( p < 0.001 ) . A clinical effect of treatment was recorded in 72 % of the subjects using terbinafine 1 % solution and 26 % of those receiving placebo ( p < 0.001 ) . We conclude that terbinafine 1 % solution is an effective and safe local treatment modality for pityriasis versicolor Background : The new antifungal triazoles itraconazole and fluconazole have revolutionized the treatment of pityriasis versicolor . Both drugs have shown promising results in different dose schedules . Objective : To compare the efficacy and safety of single oral dose treatment with fluconazole versus itraconazole in patients with pityriasis versicolor . Methods : A total of 40 patients with pityriasis versicolor were allocated r and omly to group A and group B. A single dose of fluconazole ( 400 mg ) or itraconazole ( 400 mg ) was given orally to group A or group B patients , respectively . Patients were assessed mycologically by KOH and culture . Culture was done from lesional and perilesional skin to quantify growth and to observe the effect of these drugs and the persistence/reappearance of the fungus in relation to relapse at 2 and 8 weeks . Relapse was defined as reappearance or worsening of clinical signs and symptoms or positive KOH/culture after initial improvement . Results : Thirteen ( 65 % ) patients in the fluconazole group and 4 ( 20 % ) patients in the itraconazole group became culture negative at the end of 8 weeks . Relapse was found to be higher in the itraconazole group compared to the fluconazole group ( 60 vs. 35 % ) . A direct correlation was found between the relapse rate and positivity of perilesional skin for Malassezia furfur . Conclusion : In the same dosing , fluconazole was found to be more effective than itraconazole ; however , both drugs were found to be safe Terbinafine ( Lamisil ) is the newest compound within a class of antimycotic drugs called allylamines . It is active against a broad range of dermatophytes and yeasts and exerts its fungicidal action by inhibiting squalene epoxidation during sterol synthesis in fungal membranes . Effective therapy ( complete cure or mycological cure with minimal signs and symptoms ) has been observed in 70–90 % of 1200 patients treated topically with 1 % cream for tinea corporis/cruris , tinea pedis , cutaneous c and idiasis and pityriasis versicolor . Cure in patients treated systemically ( 125 mg b.i.d . orally ) has been documented to be 75–90 % in tinea corporis and chronic tinea pedis ( plantar type ) , 60–70 % in cutaneous c and idiasis , and 90–100 % in onychomycosis . Particularly noteworthy is the low rate of relapse of infection after cure of chronic dermatophyte infections , since frequent relapse is a recognized problem with presently available antifungal drugs , Terbinafine is ineffective when used systemically for pityriasis versicolor . Side‐effects following oral administration of the recommended dose of 125 mg b.i.d . include gastrointestinal symptoms ( 3–4 % ) , allergy ( 1 % ) , and miscellaneous mild non‐specific symptoms ( 1 % ) . No significant haematological , hepatic or renal effects have been observed . Based on the drug 's fungicidal action and the early appearance of negative cultures in these studies , a short duration therapy is predicted to be effective BACKGROUND : Itraconazole is an oral antifungal agent , which has been proved to be effective in pityriasis versicolor . Different regimens for the treatment of pityriasis versicolor have been studied and good results were obtained with short-term treatment regimens . OBJECTIVE : To compare the efficacy and tolerability of the classical regimen of 200 mg/day itraconazole for 5 days with the regimes of 400 mg/day for 1 and 3 days . METHODS : A total of 60 patients with pityriasis versicolor were recruited into a r and omized study . The patients were divided into three groups , each composed of 20 people . Mycological and clinical assessment s were done before and on the 7th and 28th days after treatment . Results were evaluated with the chi-squared test . RESULTS : The regimen of 400 mg/day itraconazole for 3 days was found to be as effective as the classical regimen of 200 mg/day for 5 days in the treatment of pityriasis versicolor . The regimen of 400 mg/day itraconazole for 1 day was found to be ineffective . CONCLUSION : This study has shown that a short course of itraconazole , 400 mg/day for 3 days , appears to be an effective and alterantive treatment for pityriasis versicolor Pityriasis versicolor can be treated by a single or multiple dosage regime of ketoconazole as well as by fluconazole . The therapeutic efficacy of these two drugs has not been compared . One hundred and eighty patients with moderate to extensive pityriasis versicolor confirmed by KOH and Wood 's lamp examination were r and omly assigned to one of the four oral antifungal regimes : Ketoconazole 400 mg single dose ( Category I ) , Ketoconazole 200 mg daily for 10 days ( Category II ) , Fluconazole 400 mg single dose ( Category III ) or Fluconazole 150 mg per week for 4 weeks ( Category IV ) . Follow up was done at 2 and 4 weeks and then at 3 , 6 and 12 months after the treatment in each group . KOH and Wood 's lamp examinations were repeated each time . After four weeks of treatment , clinical cure was observed in 66.6 % ( Category I ) , 73.3 % ( Category II ) , 80 % ( Category III ) and 59.9 % ( Category IV ) of patients . Mycological cure after four weeks of treatment was observed in 53.3 % ( Category I ) , 73.3 % ( Category II ) , 82.2 % ( Category III ) and 64.4 % ( Category IV ) of patients . After twelve months of follow-up , maximum relapses were observed with Category I. No relapse was seen in Category III patients . The time period of relapse varied from three to ten months . In conclusion , single dose 400 mg oral fluconazole provided the best clinical as well as mycological cure rate with no relapse during twelve months of follow-up BACKGROUND Pityriasis ( tinea ) versicolor is a superficial fungal infection of the stratum corneum caused by Malassezia species . The diagnosis is made clinical ly by its classic appearance of round or oval macules with fine scale that may be hyperpigmented or hypopigmented . Diagnosis may also be confirmed with microscopic evaluation of skin scrapings that reveal both short , stubby hyphae , and spores under KOH preparation . Ketoconazole is an important treatment of pityriasis versicolor but is primarily used in cream formulas . A foam vehicle has been shown to improve drug absorption through the stratum corneum and distribution in the skin . This study has assessed the safety and efficacy of ketoconazole 2 % foam in treatment of pityriasis versicolor . METHODS Ketoconazole 2 % foam was evaluated in a single-center , open-label , one-arm pilot study which enrolled eleven subjects to gain 10 evaluable subjects aged 21 years and older with a clinical diagnosis of tinea versicolor and positive KOH using calcofluor . The subjects came for 4 scheduled visits ( baseline , week 1 , week 2 , and week 4 ) and were instructed to apply ketoconazole 2 % foam to all affected areas twice daily for 2 weeks . At each visit , mycological and clinical assessment of a target area was done , along with static global assessment and body surface area estimation of the disease in each subject . Patient question naires were given at baseline and at week 2 to rate pruritus and satisfaction with the foam . RESULTS At the week 2 visit , following the treatment period , three out of ten evaluable subjects had negative skin sample s prepared with KOH/calcifluor . Of these three , one subject later showed recurrence of fungal elements consistent with tinea versicolor at the week 4 follow-up visit . The other negative subjects remained negative and four additional subjects tested negative at week 4 . Three subjects with positive sample s at week 4 had only yeast forms without hyphae present . Investigator ratings of the target area were averaged for each clinical feature and demonstrated improvement in scale , hyper- or hypopigmentation , erythema , and in duration throughout the study . Average pruritus score increased slightly 1 week after the baseline visit , but then improved steadily over the remaining visits . The investigator 's static global assessment rating showed improvement from mild to moderate disease at baseline to minimal or no disease at week 4 in 7 subjects . The remaining subjects showed neither improvement nor progression of the disease throughout the study . One out of the eleven subjects enrolled did not complete the study . One subject noted mild skin burning sensation after application of medicine . Post-treatment patient question naires indicated overall satisfaction with the foam vehicle . LIMITATIONS This was a single-arm , open-label , noncomparative trial . CONCLUSION Ketoconazole 2 % foam improved overall clinical assessment and microscopic evidence of pityriasis versicolor in all subjects with favorable patient feedback regarding the novel foam vehicle This study was design ed to assess the efficacy , tolerability , and safety of oral fluconazole given at 300 mg once weekly for two weeks in the treatment of tinea versicolor . Enrolled into the study were 44 subjects with tinea versicolor , provisionally confirmed by the detection of fungal hyphae in KOH wet mounts and Wood 's lamp examination . Four subjects were classified as dropouts because no information was obtained from them after the baseline visit . Subjects were treated for two weeks orally with fluconazole 300 mg weekly and followed at the 1st , 2nd , 4th and 12th weeks of treatment . The study included 40 subjects ( 26 males and 14 females , mean age 29 years , range 19 - 48 years ) . At the week 4 visit , 30 ( 75 % ) patients showed a complete cure and 31 ( 77.5 % ) patients showed mycologic cure . Ten ( 25 % ) patients had no significant response to therapy . At the final follow-up visit ( week 12 ) , none of the patients showing complete or mycologic cures exhibited a recurrence . No adverse effects were observed in any of the patients treated . We believe that , due to the low incidence of side effects , shorter treatment duration , and increased adaptation of the patients , fluconazole can be used in the treatment of tinea versicolor with confidence BACKGROUND Pityriasis ( tinea ) versicolor has a high tendency to recur after being treated successfully . Prophylactic treatment to reduce recurrence is needed . OBJECTIVE To determine whether recurrence of pityriasis versicolor could be prevented by prophylactic itraconazole treatment . DESIGN Open treatment followed by a r and omized , double-blind , placebo-controlled phase . SETTING Multinational outpatient centers . PATIENTS A total of 239 consecutive patients were included ; 238 started open treatment . A total of 209 patients started prophylactic treatment : 106 in the itraconazole group and 103 in the placebo group . INTERVENTIONS Open treatment : itraconazole , 200 mg once daily for 7 days . Prophylactic treatment : itraconazole , 200 mg , or placebo twice daily 1 day per month for 6 consecutive months . MAIN OUTCOME MEASURES Mycological cure rates at the end of open treatment and at the end of prophylactic treatment . RESULTS Mycological cure at the end of open treatment was 92 % ( 205/223 ) . At the prophylactic treatment end point ( 6 months ) , mycological cure was 88 % ( 90/102 ) in the itraconazole group and 57 % ( 56/99 ) in the placebo group ( P<.001 ) . In open treatment , 11 patients were not able to be evaluated for efficacy . In prophylactic treatment , 4 patients in the itraconazole group and 4 in the placebo group were not able to be evaluated . Adverse events were reported during open treatment by 26 patients ( 11 % ) and during prophylactic treatment by 17 ( 16 % ) in the itraconazole group and 14 ( 14 % ) in the placebo group . No patients experienced any serious adverse events . CONCLUSIONS Prophylactic itraconazole treatment is efficacious for pityriasis versicolor after 6 months , as is itraconazole in the treatment of pityriasis versicolor Background : Ketoconazole is a typical treatment available for pityriasis versicolor ; tretinoin cream is effective , too . Adapalene gel is a tretinoin derivative and has a lower incidence of irritation compared with other topical retinoid products . However , there are no reports on adapalene gel for the treatment of pityriasis versicolor . Objective : To study the effect of adapalene gel comparing the treatment with adapalene gel and 2 % ketoconazole cream in pityriasis versicolor . Methods : Eighty patients suffering from pityriasis versicolor were r and omly divided into two groups ; one group were treated with 2 % ketoconazole cream topically twice daily for 2 weeks , adapalene gel was used for the other group in a similar fashion . Results : There were no significant differences in efficacy between the two groups . No major side effects were noted in any of the groups either . Conclusion : Adapalene was the favorable option in the treatment of pityriasis versicolor . The probable therapeutic mechanism of adapalene is also discussed During the first three years of clinical investigation of itraconazole , more than 1,000 patients with mycoses were treated with the drug . Almost 50 % were women with vaginal c and idosis ; a dosage of 200 mg per day for three days appeared to be optimal for their treatment . Several treatment regimens were tested for pityriasis versicolor ; the minimum total dose necessary for optimal results was 1 g. A r and omized comparison of 50-mg and 100-mg daily doses for the treatment of skin mycoses indicated that the optimal dosage is 100 mg . The results of short courses of treatment for superficial dermatophytoses suggest that such regimens may be effective , and the results of an ongoing double-blind comparison of itraconazole and griseofulvin suggest that itraconazole is superior in these infections . The outcome of treatment of systemic mycoses with itraconazole , especially sporotrichosis , chromomycosis , and aspergillosis , indicates that itraconazole may be useful in therapy for life-threatening fungal infections when st and ard therapy has failed BACKGROUND Pramiconazole is a broad-spectrum triazole antifungal with potential for oral treatment of pityriasis versicolor . OBJECTIVE We sought to assess the efficacy and tolerability of 5 doses of pramiconazole relative to placebo . METHODS This was a r and omized , multicenter , double-blind , placebo-controlled , 28-day , dose-finding study . A total of 147 patients were r and omized to treatment with placebo or one of 5 doses of pramiconazole ; treatment lasted for 3 consecutive days . Efficacy was based on mycological response , severity of clinical signs and symptoms , and the Investigator Global Assessment of lesion clearance . RESULTS A statistically significant ( P < .001 ) dose-dependent effect was observed . When compared with placebo , a significant response ( P < .05 ) was obtained for all but the lowest single dose of pramiconazole . There were no serious , treatment-related adverse events or other safety concerns . LIMITATIONS The follow-up period was limited to 1 month after treatment onset . CONCLUSIONS Pramiconazole is a well-tolerated and effective treatment for pityriasis versicolor and the most effective treatment regimen in this study included 200 or 400 mg taken once , and 200 mg taken once daily for 2 or 3 days Ninety patients with tinea versicolor were r and omly assigned to treatment with either a single 450-mg dose of fluconazole , two 300-mg doses of fluconazole given 1 week apart , or itraconazole 200 mg daily for 7 days . At the end of treatment , the cure rate for itraconazole ( 20 % ) was significantly higher ( P = 0.024 ) than that for fluconazole 450 mg ( 0 % ) . When cure plus improvement was considered , response rates among the three treatment groups were comparable ( 97 , 100 , and 97 % for fluconazole 450 mg , fluconazole 300 mg , and itraconazole , respectively ) . Failure rates at the end of treatment were low ( 0–3 % ) . Clinical response rates achieved at the end of treatment generally were maintained at 1 month , but tended to decrease at 2 months . Eradication at the end of treatment was not significantly different among the treatment groups ( 17 , 33 , and 38 % for fluconazole 450 mg , fluconazole 300 mg , and itraconazole , respectively ) . At 1 month , the eradication rate was significantly higher ( P = 0.012 ) for the two-dose than the single-dose fluconazole treatment group ( 97 and 70 % , respectively ) . At 2 months , reinfection rates were 21 , 20 , and 4 % for fluconazole 450 mg , fluconazole 300 mg , and itraconazole , respectively . No clinical adverse events occured , and no patients were withdrawn for laboratory abnormalities Twenty-eight patients with pityriasis versicolor were treated orally with 200 mg of itraconazole per day in an open , r and omized comparison of five-day and seven-day treatment regimens . The morphologic changes in Malassezia furfur produced by treatment were confirmed by studies with transmission and scanning electron microscopy . The clinical results showed that seven days of treatment were more effective than five days . Transmission electron microscopy revealed cytopathic changes in the fungus at the end of treatment , intracellular necrosis being complete within seven to 28 days . Cell-surface alterations detected by scanning electron microscopy developed more slowly -- maximal changes were observed 14 days after the beginning of treatment . One patient developed nausea during treatment ; no other adverse effects were attributed to the drug BACKGROUND : A number of effective topical therapies are available for the treatment of tinea versicolor ( TV ) . However , topical antifungals are difficult to apply to a large body surface area and for this reason TV is perhaps more easily treated with systemic agents . METHODS : A total of 128 patients with TV , aged 15 - 55 years , were entered into a r and omized , double-blind , clinical trial comparing the efficacy and tolerance of two regimens of oral treatment for TV . The patients were r and omly divided in two groups : group 1 received two 150 mg capsules of fluconazole in a single dose repeated weekly for 2 weeks ; and group 2 received two 200 mg tablets of ketoconazole in a single dose repeated weekly for 2 weeks . Diagnosis of TV was made clinical ly by direct KOH preparation and Wood 's lamp examination . RESULTS : Of 128 patients , 100 completed the study and no major side-effects were noted between the two treatment regimens . Results of the study showed no significant differences in efficacy , safety and tolerability between the two treatment regimens . The maximal cure rate was achieved at 8 weeks from the start of treatment and decreased slightly afterwards . CONCLUSIONS : Fluconazole and ketoconazole demonstrated similar efficacy in the treatment of TV . We also demonstrated a lack of correlation between mycological cure and hypopigmentation at the end of treatment ( 2 weeks ) and the usefulness of Wood 's lamp examination in detecting cure of TV Topical drugs are often effective in limited lesions of pityriasis versicolor ; but in extensive cases , systemic drugs are more suitable . Previous studies have shown that ketoconazole and fluconazole are effective in 42 - 97 % and 74 - 100 % of lesions respectively . Our purpose was to compare the effectiveness of a single dose of 400 mg ketoconazole with two doses of 300 mg of fluconazole with 2 weeks interval . Ninety patients with extensive pityriasis versicolor ( body involved area > or = 25 % ) were r and omly assigned to treatment with either a single dose of 400 mg of ketoconazole or with two doses of 300 mg of fluconazole with 2 weeks interval . One month after the treatment , the improvement rate and side effects were evaluated by clinical examination and question naire . Sixty cases ( 66.7 % ) completed the study . They were 51 males and nine females , with a mean age of 30 years . At the follow-up visit ( 1 month after the end of treatment ) , the improvement rate for ketoconazole ( 87.9 % ) was not significantly different from fluconazole ( 81.5 % ) , ( Fisher test : P = 0.37 ) . Due to the hepatotoxicity of ketoconazole , fluconazole appears to be more suitable in the treatment of extensive pityriasis versicolor In a double blind r and omised study to assess the efficacy of single dose fluconazole therapy , 30 patients of tinea versicolor ( TV ) were enrolled and were assigned into 2 groups . Group A ( n=18 ) received fluconazole 400 mg single dose orally and Group B ( n=12 ) received placebo . At the end of 2 weeks , 8 out of 18 ( 44.4 % ) of Group A patients and 1 out of 12 ( 8.3 % ) of Group B showed mycological cure ( P=0.08 ) . Ten patients of Group A who had KOH positivity after 2 weeks were given 2nd dose of 400 mg fluconazole 2 weeks after the 1st dose . Nine of these ( 90 % ) showed mycological cure at the end of subsequent 2 weeks . The difference between the efficacy of single dose fluconazole after 2 weeks and 2 doses of fluconazole after 4 weeks was statistically significant ( P<0.01 ) . None of the patients had any significant side effects . Therefore single dose therapy of fluconazole 400 mg is not satisfactory in TV . Instead , 2 doses of flluconazole ( 400 mg ) given at 2 weeks intervals is safe and very effective Pityriasis versicolor is a chronic superficial fungal disease usually located on the upper trunk , neck or upper arms . Terbinafine is an orally and topically active allylamine antifungal derivative with a broad antifungal spectrum . Several studies have documented the high activity of terbinafine ( Lamisil ) cream in the treatment of pityriasis versicolor , with cure rates of 79 - 100 % after 2 - 4 weeks of treatment . Lamisil emulsion gel ( Lamisil DermGel ) is a new topical formulation that remains in the skin in high concentrations for several months after just 1 week of application . Recently , in a prospect i ve , double-blind , placebo-controlled , r and omised , parallel-group , comparative , multicentre study , we have treated patients with pityriasis versicolor with either terbinafine 1 % emulsion gel ( Lamisil DermGel ) or placebo gel . Sixty-one patients were included , 31 in the Lamisil DermGel group and 30 in the placebo gel group . The gel was applied once daily for 7 days and the patients were followed up for 8 weeks . Twenty-eight patients in the active and 29 patients in the placebo group were evaluable for efficacy . Using the intent-to-treat efficacy analysis , 21/28 ( 75 % ) were cured in the Lamisil-DermGel-treated group compared to 4/29 ( 14 % ) in the placebo group . No side-effects were seen . In conclusion , Lamisil DermGel was well tolerated and superior to placebo in the treatment of pityriasis versicolor when applied once daily for 7 days This study was design ed to compare the therapeutic effects of topical clotrimazole and systemic fluconazole in pityriasis versicolor . A double-blind r and omized controlled trial was carried out in the dermatological clinic of Gorgan , northern Iran , between April 2006 and May 2007 . All consecutive patients with pityriasis versicolor were included and r and omly divided into two groups . In the first group ( G1 ) , patients underwent treatment with a single dose of fluconazole capsule ( 400 mg ) and placebo cream . In the second group ( G2 ) , patients underwent treatment with clotrimazole cream ( twice daily ) and placebo capsule . The course of treatment was 2 weeks . All subjects were re-evaluated 2 , 4 and 12 weeks after the end of the therapeutic course . After 2 weeks , the rate of complete resolution of disease was significantly higher in G2 than G1 ( 49.1 % vs 30 % ) . After 4 weeks , 41 patients ( 81.2 % ) of G1 and 52 patients ( 94.9 % ) of G2 showed complete resolution . After 12 weeks , 46 patients ( 92 % ) in G1 and 45 patients ( 81.8 % ) in G2 showed complete resolution . Recurrence rate in G1 and G2 were 6 % and 18.2 % , respectively . No complications were seen in either group . In this study , clinical response at week 4 was greater in the clotrimazole group than the fluconazole group . Recurrence at week 12 after treatment was less with oral fluconazole than clotrimazole cream . So , for better evaluation , more studies need to be done |
12,947 | 26,431,423 | High heterogeneity aside , pooled results from the meta-analyses reflected a consistent , moderate-to-large effect of decreased high-frequency HRV in chronic pain , implicating a decrease in parasympathetic activation .
These effects were heavily influenced by fibromyalgia studies . | Both sympathetic and parasympathetic nervous systems are involved in regulating pain states .
The activity of these systems seems to become disturbed in states of chronic pain .
This disruption in autonomic balance can be measured through the assessment of heart rate variability ( HRV ) , that is , the variability of the interval between consecutive heart beats .
However , there is yet to be a systematic evaluation of the body of literature concerning HRV across several chronic pain conditions .
Moreover , modern meta-analytical techniques have never been used to vali date and consoli date the extent to which HRV may be decreased in chronic pain . | Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items OBJECTIVE To determine the prevalence and characteristics of fibromyalgia in the general population . METHODS A r and om sample of 3,006 persons in Wichita , KS , were characterized according to the presence of no pain , non-widespread pain , and widespread pain . A sub sample of 391 persons , including 193 with widespread pain , were examined and interviewed in detail . RESULTS The prevalence of fibromyalgia was 2.0 % ( 95 % confidence interval [ 95 % CI ] 1.4 , 2.7 ) for both sexes , 3.4 % ( 95 % CI 2.3 , 4.6 ) for women , and 0.5 % ( 95 % CI 0.0 , 1.0 ) for men . The prevalence of the syndrome increased with age , with highest values attained between 60 and 79 years ( > 7.0 % in women ) . Demographic , psychological , dolorimetry , and symptom factors were associated with fibromyalgia . CONCLUSION Fibromyalgia is common in the population , and occurs often in older persons . Characteristic features of fibromyalgia -- pain threshold and symptoms -- are similar in community and clinic population s , but overall severity , pain , and functional disability are more severe in the clinic population Pain is a syndrome characterized by several neurophysiological changes including that of the autonomic nervous system . Chronic low back pain ( LBP ) is a major health problem and is a frequent reason for using unconventional therapies especially acupuncture . This study was conducted to evaluate the autonomic status and pain profile in chronic LBP patients and to observe the effect of electro acupuncture therapy . Chronic LBP patients ( n=60 ) were recruited from the Department of Orthopaedics , GTB Hospital , Delhi . Age and sex matched healthy volunteers were selected as controls ( n=30 ) . Following a written consent , LBP patients were r and omly allocated into two study groups - Group A received 10 sittings of electro acupuncture , on alternate days , at GB and UB points selected for back pain , while the Group B received a conventional drug therapy in the form of oral Valdecoxib together with supervised physiotherapy . Controls were assessed once while the patients were assessed twice , before and after completion of the treatment program ( 3 weeks ) . The autonomic status was studied with non-invasive cardiovascular autonomic function tests which included E : I ratio , 30:15 ratio , postural challenge test and sustained h and grip test . Pain intensity was measured with the visual analogue scale ( VAS ) and the global perceived effect ( GPE ) . Statistical analysis was performed using repeated measure 's ANOVA with Tukey 's test . Pain patients showed a significantly reduced vagal tone and increased sympathetic activity as compared to the controls ( P<0.05 to P<0.001 in different variables ) . Following treatment , both the study groups showed a reduction in vagal tone together with a decrease in the sympathetic activity . There was also a considerable relief of pain in both groups , however , the acupuncture group showed a better response ( P<0.01 ) . We conclude that there is autonomic dysfunction in chronic LBP patients . Acupuncture effectively relieves the pain and improves the autonomic status and hence can be used as an alternative/additive treatment modality in these cases The aim of the present study was to investigate reactions in trapezius muscle blood flow ( MBF ) , muscle activity , heart rate variability ( HRV ) and systemic blood pressure ( BP ) to autonomic tests in subjects with chronic neck – shoulder pain and healthy controls . Changes in muscle activity and blood flow due to stress and unfavourable muscle loads are known underlying factors of work-related muscle pain . Aberration of the autonomic nervous system ( ANS ) is considered a possible mechanism . In the present study , participants ( n = 23 Pain , n = 22 Control ) performed autonomic tests which included a resting condition , static h and grip test ( HGT ) at 30 % of maximal voluntary contraction , a cold pressor test ( CPT ) and a deep breathing test ( DBT ) . HRV was analysed in time and frequency domains . MBF and muscle activity were recorded from the upper trapezius muscles using photoplethysmography and electromyography ( EMG ) . The pain group showed reduced low frequency-HRV ( LF ) and SDNN during rest , as well as a blunted BP response and increased LF-HRV during HGT ( ∆systolic 22 mm Hg ; ∆LF(nu ) 27 % ) compared with controls ( ∆systolic 27 ; ∆LF(nu ) 6 % ) . Locally , the pain group had attenuated trapezius MBF in response to HGT ( Pain 122 % Control 140 % ) with elevated trapezius EMG following HGT and during CPT . In conclusion , only HGT showed differences between groups in systemic BP and HRV and alterations in local trapezius MBF and EMG in the pain group . Findings support the hypothesis of ANS involvement at systemic and local levels in chronic neck – shoulder pain UNLABELLED Several case-control studies have been conducted that examine the association between autonomic variables and persistent pain conditions ; however , there is a surprising dearth of published studies in this area that have focused on temporom and ibular disorders ( TMD ) . The current study presents autonomic findings from the baseline case-control study of the OPPERA ( Orofacial Pain : Prospect i ve Evaluation and Risk Assessment ) cooperative agreement . Measures of arterial blood pressure , heart rate , heart rate variability , and indirect measures of baroreflex sensitivity were assessed at rest and in response to a physical ( orthostatic ) and psychological ( Stroop ) stressors in 1,633 TMD-free controls and 185 TMD cases . In bivariate and demographically adjusted analyses , greater odds of TMD case status were associated with elevated heart rates , reduced heart rate variability , and reduced surrogate measures of baroreflex sensitivity across all experimental procedures . Principal component analysis was undertaken to identify latent constructs revealing 5 components . These findings provide evidence of associations between autonomic factors and TMD . Future prospect i ve analyses in the OPPERA cohort will determine if the presence of these autonomic factors predicts increased risk for developing new onset TMD . PERSPECTIVE This article reports autonomic findings from the OPPERA Study , a large prospect i ve cohort study design ed to discover causal determinants of TMD pain . Findings indicate statistically significant differences between TMD cases and controls across multiple autonomic constructs at rest and during both physical and psychologically challenging conditions . Future analyses will determine whether these autonomic factors increase risk for new onset TMD OBJECTIVE To determine the accumulated 24-hour cardiovascular autonomic modulation and its circadian variations in patients with fibromyalgia , by means of heart rate variability analysis . METHODS Thirty patients with fibromyalgia and 30 age- and sex-matched controls were studied prospect ively . Assessment s included a 24-hour ambulatory recording of heart rate variability , time-domain analysis of the accumulated 24-hour R-R interval variations , and power spectral analysis to determine the sympatho/ vagal balance at different hours ( calculated as the power spectral density of the low-frequency [ 0.04 - 0.15-Hz ] sympathetic b and divided by the power of the high-frequency [ 0.15 - 0.50-Hz ] parasympathetic b and ) . RESULTS Fibromyalgia patients had diminished accumulated 24-hour heart rate variability , manifested by a decreased st and ard deviation of all R-R intervals ( mean + /- SD 126 + /- 35 ms , versus 150 + /- 33 ms in controls ; P = 0.008 ) and a decreased ratio of pairs of adjacent R-R intervals differing by > 50 ms ( mean + /- SD 12.0 + /- 9.0 % versus 20.1 + /- 18.0 % ; P = 0.031 ) . Patients lost the circadian variations of sympatho/vagal balance , with nocturnal values significantly higher than those of controls at time 0 ( mean + /- SD 3.5 + /- 3.2 versus 1.2 + /- 1.0 ; P = 0.027 ) and at 3 hours ( 3.3 + /- 3.0 versus 1.6 + /- 1.4 ; P = 0.01 ) . CONCLUSION Individuals with fibromyalgia have diminished 24-hour heart rate variability due to an increased nocturnal predominance of the low-frequency b and oscillations consistent with an exaggerated sympathetic modulation of the sinus node . This abnormal chronobiology could explain the sleep disturbances and fatigue that occur in this syndrome . Spectral analysis of heart rate variability may be a useful test to identify fibromyalgia patients who have dysautonomia Heart rate variability ( HRV ) is a vagal nerve-mediated biomarker of cardiac function used to investigate chronic illness , psychopathology , stress and , more recently , attention-regulation processes such as meditation . This study investigated HRV in relation to maladaptive perfectionism , a stress-related personality factor , and mindfulness meditation , a stress coping practice expected to elevate HRV , and thereby promote relaxation . Maladaptive perfectionists ( n=21 ) and Controls ( n=39 ) were exposed to a lab-based assessment in which HRV was measured during ( 1 ) a 5-minute baseline resting phase , ( 2 ) a 5-minute cognitive stress-induction phase , and ( 3 ) a post-stress phase . In the post-stress phase , participants were r and omly assigned to a 10-minute audio-instructed mindfulness meditation condition or a 10-minute rest condition with audio-description of mindfulness meditation . Analyses revealed a significant elevation in HRV during meditation for Controls but not for Perfectionists . These results suggest that mindfulness meditation promotes relaxation following cognitive stress and that the perfectionist personality hinders relaxation possibly because of decreased cardiac vagal tone . The results are discussed in the context of developing psychophysiological models to advance therapeutic interventions for distressed population |
12,948 | 29,197,438 | Conclusions Based on the clinical outcomes , the results of this systematic review and meta‐ analysis showed that soft tissue alternatives result in an increased width of KT . | Objectives This systematic review and meta‐ analysis aim ed to compare clinical outcomes and width of keratinized tissue ( KT ) around teeth , following the soft tissue alter‐ natives and free gingival graft ( FGG ) procedures . | BACKGROUND Freeze-dried acellular dermal matrix ( ADM ) allograft , originally used for full-thickness burn wounds , was recently introduced as an alternative to the autogenous free gingival graft ( FGG ) in achieving increased attached keratinized tissue . The aim of part 1 of this study was to investigate the clinical efficacy of the ADM allograft for this particular purpose . METHODS Twelve patients , 7 males and 5 females , with attached gingiva < or = 1 mm on the facial aspect of m and ibular anterior teeth demonstrating a tendency of progressive marginal tissue recession , were r and omly assigned to either test or control treatment . Six patients received ADM graft ( test ) and 6 patients received an autogenous FGG harvested from the hard palate ( control ) . Clinical variables including plaque index ( PI ) , gingival index ( GI ) , probing depth ( PD ) , attached tissue width ( AT ) , and gingival recession ( GR ) were recorded immediately before surgery and at the 6-month postoperative visit . Patients were seen at 2 , 4 , 6 , 8 , and 12 weeks to monitor wound healing and oral hygiene performance ( PI and GI ) . Graft width was also measured , in corono-apical direction , on individually involved teeth during the surgery . RESULTS When values between baseline and 6 months were compared in both groups , there was no statistically significant difference in changes of PI , GI , PD , and GR ( P>0.05 ) with the exception of PD in the FGG group ( 1.01 + /- 0.03 versus 1.27 + /- 0.20 mm , P= 0.042 ) . There was a statistically significant ( P < 0.05 ) increase in AT in both groups . Although the ADM group received wider grafts than the FGG group ( 8.81 + /- 0.46 versus 6.70 + /- 0.89 mm ) , the AT gain was significantly smaller ( 2.59 + /- 0.92 versus 5.57 + /- 0.44 mm ) and the graft shrinkage significantly greater ( 71 + /- 10 % versus 16 + /- 12 % ) in the ADM group than in the FGG group ( P<0.01 ) . CONCLUSIONS The results of this study suggest that in procedures aim ing at increasing the width of attached gingiva : 1 ) the ADM allograft was less effective and less predictable than the autogenous FGG in terms of increasing attached keratinized tissue due to considerable shrinkage and inconsistent quality of the attached tissue gained and 2 ) the esthetic results using the ADM allograft might be better than those using the autogenous FGG BACKGROUND Periodontists have found the gingival autograft to be an effective and predictable technique to increase the amount of attached gingiva around teeth , but this technique requires the surgeon to harvest donor tissue from a remote surgical site . The present study seeks to evaluate the safety and effectiveness of a tissue-engineered skin equivalent , a living human fibroblast-derived dermal substitute ( HF-DDS ) , compared to a gingival autograft ( GA ) consisting of donor tissue harvested from the patient 's palate in a procedure design ed to increase the amount of keratinized tissue around teeth that do not require root coverage . METHODS Twenty-five patients with insufficient attached gingiva associated with at least two teeth in contralateral quadrants of the same jaw were treated . One tooth in each patient was r and omized to receive either a GA ( control ) or a HF-DDS graft ( test ) . Clinical parameters measured at baseline and 3 , 5 , 7 , 9 , and 12 months included recession , clinical attachment level , keratinized tissue height , and plaque index . Probing depth was measured at 7 , 9 , and 12 months . Inflammation of each site was scored and texture and color of the grafted tissue were compared to the surrounding tissue . Resistance to muscle pull was evaluated and a question naire was used to determine patient preference . Surgical position of the graft and alveolar bone level were recorded at the surgical visit and patients were evaluated weekly for the first 4 weeks at which time recession and level of oral hygiene were measured . Biopsies and persistence studies were performed on a subset of the patients . RESULTS Results for both test and control groups were similar for all measured clinical parameters with the exception of amount of keratinized tissue and percent shrinkage of keratinized tissue . The control group exhibited an average of 1.0 to 1.2 mm more keratinized tissue over time than the test group ( P < 0.001 ) and the control group had about half as much shrinkage as the test group over time ( P < 0.001 ) . Test sites demonstrated significantly better color match over time compared to control sites . Similarly , tissue texture for test sites was significantly better than control sites over time . CONCLUSIONS Based on the results of this investigation , the tissue engineered HF-DDS graft was safe and capable of generating keratinized tissue without the morbidity and potential clinical difficulties associated with donor site surgery . The GA generated more keratinized tissue and shrank less than the HF-DDS graft , but the test graft generated tissue that appeared more natural BACKGROUND This study evaluated the safety and effectiveness of a tissue-engineered skin product composed of viable neonatal keratinocytes and fibroblasts and compared it to a free gingival graft ( FGG ) in a procedure to enhance keratinized tissue ( KT ) and wound healing around teeth that do not require root coverage . METHODS Twenty-five subjects were enrolled who had at least two non-adjacent teeth in contralateral quadrants exhibiting an insufficient zone of attached gingiva requiring soft tissue grafting where root coverage was not desired . One tooth was r and omized to receive an FGG , and the other was r and omized to receive bilayered cell therapy ( BCT ) . The amount of KT was measured at baseline and 3 and 6 months , and the texture and color of the grafted tissue were compared to the surrounding tissue at months 1 , 3 , and 6 . A question naire was used to determine subject preference at 6 months . Biopsies and persistence studies were performed on a subset of the subjects . RESULTS The FGG generated statistically significantly ( P < 0.001 ) more KT than the test device ( BCT ) ( 4.5 + /- 0.80 mm versus 2.4 + /- 1.02 mm ) ; no significant difference in recession or clinical attachment level was detected between treatment groups ( P = 0.212 and P = 0.448 , respectively ) ; and no significant differences were detected at any time point for bleeding on probing ( BOP ) , resistance to muscle pull , or inflammation . The BCT group had significantly better color and texture match with surrounding tissue ( P < 0.001 ) , and subject preference was significantly greater for the BCT group ( P = 0.041 ) . No device-related adverse events or safety issues occurred during the course of the study . CONCLUSIONS The tissue-engineered graft BCT was safe and capable of generating de novo KT without the morbidity and potential clinical difficulties associated with donor-site surgery . The amount of KT generated with FGG was greater than generated with BCT ; however , 24 of 25 test sites demonstrated an increase in KT at 6 months , with more than three-quarters of the sites yielding > or = 2 mm b and s of KT 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 This study was conducted to compare the efficacy and feasibility of an extracellular matrix membrane ( DynaMatrix ) with that of an autogenous gingival graft in increasing the width of attached keratinized tissue . Six patients with an inadequate amount of attached keratinized gingiva on the bilateral facial aspect of the m and ibular posterior teeth were recruited for this study . The defect sites were r and omly subjected to receive either test ( DynaMatrix membrane ) or control ( autogenous gingival graft ) treatment . Both test and control sites achieved a clinical ly significant increase in the amount of keratinized gingiva , and the DynaMatrix membrane-treated sites blended well with the surrounding tissue , with a better appearance when compared to the autogenous gingival grafted sites . The biopsy specimens of both test and control sites appeared to be similar histologically , with mature connective tissue covered by keratinized epithelium . The results of both clinical and histologic evaluations have suggested a potential application of an extracellular matrix membrane in achieving gingival augmentation BACKGROUND The aim of this study was to evaluate clinical ly , histologically , and ultrastructurally the integration process of the acellular dermal matrix used to increase the b and of keratinized tissue while achieving gingival inflammation control . METHODS Ten patients exhibiting a mucogingival problem with b and s of keratinized tissue < or=1 mm and gingival inflammation of the related teeth were included in the study . The surgical procedures were performed to augment the gingival tissue using acellular dermal matrix . Clinical measurements were assessed at baseline and after 3 months . A specimen of the allograft and surrounding tissues was obtained immediately before the surgery and 4 minutes and 1 , 2 , 3 , 4 , 6 , and 10 weeks after grafting . RESULTS Clinical ly , a gain of keratinized tissue of 2.92 + /- 0.65 mm was observed after 3 months . Histologically and ultrastructurally , many macrophages were observed phagocytosing preexisting collagen fibers in the first weeks . From week 2 on , fibroblasts synthesizing new collagen , epithelial cells colonizing the graft surface , and revascularization were noticed . After 6 weeks it was difficult to find the acellular dermal matrix preexisting collagen fibers . This process of substitution was completed after 10 weeks , when the reepithelialization of the entire graft throughout a well-structured basement membrane was achieved . CONCLUSION The acellular dermal matrix graft seemed to be an easily h and led material for use in keratinized tissue augmentation that , in humans , was substituted and completely reepithelialized in 10 weeks according to histologic and ultrastructural results This prospect i ve split-mouth pilot case series compared the use of a bilayer collagen matrix ( CM ) to an autogenous gingival graft ( AGG ) in the ability to increase the zone of keratinized attached gingiva . Five patients with inadequate amounts of keratinized attached gingiva bilaterally in the posterior m and ible were enrolled using a split-mouth design . There were statistically significant increases in attached gingiva at all test ( CM ) and control ( AGG ) sites . The CM sites at 12 months blended well with surrounding tissues , while the AGG sites were morphologically dissimilar to the adjacent areas . Biopsy results showed intrapatient histologic similarity between CM and AGG treatments , with all sites exhibiting mature connective tissue covered by keratinized epithelium . Thus , the obtained data support further investigations in evaluating the role of CM as a viable alternative to AGG in augmenting areas deficient in keratinized gingiva BACKGROUND The importance of keratinized tissue is a controversial subject . However , in some situations most clinicians would agree that surgical procedures to increase the amount of keratinized tissue without root coverage are indicated . In this study , 3 surgical procedures were compared in their ability to increase the width of keratinized tissue . They are : the epithelized autogenous masticatory mucosa graft ( free gingival graft ) , autogenous predominately connective tissue graft ( connective tissue graft ) , and acellular dermal matrix . METHODS Forty-five patients referred for treatment of areas with inadequate keratinized tissue were r and omly assigned into 1 of 3 groups of 15 each . Each group was treated with 1 of the 3 surgical procedures to increase the width of keratinized tissue . The width of keratinized tissue pre- and postsurgery was evaluated . RESULTS All 3 groups started with a similar width of keratinized tissue . All of the surgical procedures result ed in a statistically significant increase in the width of keratinized tissue : free gingival graft , 4.1 mm ; connective tissue graft , 3.6 mm ; and acellular dermal matrix , 4.1 mm . CONCLUSION A statistically significant increase in the amount of keratinized tissue was obtained with all 3 surgical procedures evaluated AIM The aim of this study was to test a new collagen matrix ( CM ) aim ed to increase keratinized gingiva/mucosa when compared with the free connective tissue graft ( CTG ) . MATERIAL AND METHODS This r and omized longitudinal parallel controlled clinical trial studied 20 patients with at least one location with minimal keratinized tissue ( < or=1 mm ) . MAIN OUTCOME MEASURE The 6-month width of keratinized tissue . As secondary outcomes , the aesthetic outlook , the maintenance of periodontal health and the patient morbidity were assessed pre-operatively at 1 , 3 and 6 months . RESULTS At 6 months , the CTG attained a mean width of keratinized tissue of 2.6 ( 0.9 ) mm , while the CM was 2.5 ( 0.9 ) mm , these differences being insignificant . In both groups , there was a marked contraction ( 60 % and 67 % , respectively ) although the periodontal parameters were not affected . The CM group had a significantly lower patient morbidity ( pain and medication intake ) as well as reduced surgery time . CONCLUSIONS These results prove that this new CM was as effective and predictable as the CTG for attaining a b and of keratinized tissue , but its use was associated with a significantly lower patient morbidity BACKGROUND The aim of this retrospective long-term split-mouth study was to compare the periodontal conditions of sites treated with gingival-augmentation procedures to untreated homologous contralateral sites over a long period of time ( 10 to 27 years ) . METHODS Fifty-five subjects with 73 sites ( test group ) lacking attached gingiva associated with recessions were treated by means of submarginal free gingival grafts ( SMFGGs ) and marginal free gingival grafts ( MFGGs ) . The 73 contralateral homologous sites ( control group ) , with or without recession and with or without attached gingiva , were not treated . Patients were recalled every 4 months during the follow-up period ( 10 to 27 years ) . Clinical variables , including recession depth , amount of keratinized tissue ( KT ) , and probing depth ( PD ) , were measured in treated and untreated sites at baseline , at 1 year , and at the end of the follow-up period . RESULTS At the end of the follow-up period , recession was reduced in all treated sites ( 1.5 + /- 1.0 mm for SMFGG and 1.3 + /- 0.9 mm for MFGG ) , whereas it was increased in the untreated sites ( -0.7 + /- 0.7 mm for SMFGG and -1.0 + /- 0.5 mm for MFGG ) . In the treated sites , the increased KT remained quite stable during the follow-up period . PD remained stable ( 1 mm ) in the treated and untreated sites . CONCLUSIONS The sites treated with gingival-augmentation surgery showed a tendency for coronal displacement of the gingival margin with a reduction in recession . The contralateral untreated sites showed a tendency for apical displacement of the gingival margin with an increase in the existing recessions BACKGROUND An adequate width of attached gingiva is necessary to maintain healthy periodontium , especially in orthodontics or restorative treatments in periodontics . The purpose of this study was to evaluate the width of attached gingiva after clinical application of a cultured gingival graft compared to a periosteal fenestration technique . METHODS This study was conducted on nine patients ( 18 sites ) with insufficient attached gingiva adjacent to at least two teeth in contralateral quadrants of the same jaw . A small portion ( approximately 3 x 2 x 1 mm ) of attached gingiva ( epithelial + connective tissue ) was removed with a surgical blade . After culture of gingival fibroblasts , 2 x 10(5 ) cells in 250 microl nutritional medium were added to 250 microl collagen gel . One tooth in each patient was r and omized to receive a periosteal fenestration technique for gingival augmentation ( control ) or a tissue-engineered mucosal graft ( test ) . Clinical parameters measured at baseline and 3 months included width of keratinized tissue , probing depth , and width of attached gingiva . RESULTS An increased amount of keratinized tissue was seen at all treated sites after 3 months . The mean increased amount of attached gingiva was 2.8 mm at test sites and 2 mm at control sites ; this difference was significant ( P < 0.05 ) . CONCLUSION Based on the results of this investigation , the tissue-engineered mucosal graft is safe and capable of generating keratinized tissue BACKGROUND Generation of site-appropriate tissue in the oral cavity includes the restoration of the correct anatomic type , amount , and distribution of the tissue . This study is a post hoc analysis of data collected during previously published results from two r and omized clinical trials of a living cellular sheet ( LCS ; allogenic cultured keratinocytes and fibroblasts in bovine collagen ) versus a free gingival graft ( FGG ) , evaluating their ability to augment keratinized tissue or gingiva . METHODS Post hoc histologic and clinical ( photographic ) comparisons of the outcomes of treatment were performed on histologic and photographic data gathered in the two r and omized clinical trials . RESULTS Histologic findings showed that LCS-treated sites resembled gingiva rather than alveolar mucosa . Photographic analysis indicated that LCS treatment result ed in more site-appropriate tissue than FGG in terms of tissue color , with adjacent untreated tissue , absence of scar formation or keloid-like appearance , and mucogingival junction alignment . CONCLUSION Treatment of mucogingival defects with LCS result ed in the generation of tissue that is more site appropriate than tissue transplanted from the palate The treatment of mucogingival problems is one of the main objectives of periodontal treatment . The insufficient or absent gingival attachment increases the risk of development of gingival recessions . Multiple gingival augmentation techniques of varying level of success are known . The aim of this study has been to clinical ly and histologically evaluate the integration process of scaffolds composed of primary human fibroblasts derived from keratinized gingiva on collagenous carriers . Ten patients exhibiting a mucogingival problem and gingival inflammation of the related teeth were included in the study . In total , 34 teeth in the anterior part of the maxilla and the m and ible underwent treatment . Clinical ly , over a 6 month period of observation , a significant decrease in the distance from cemento-enamel junction to mucogingival junction ( CEJ-MGJ ) was revealed . Histologically , mature connective tissue covered by keratinized epithelium was found after 12 weeks . No specimens revealed an inflammatory response . A complete clinical healing was observed after 2 weeks in eight patients [ early healing index (EHI)=I ] . The results of clinical evaluation indicate that the method of primary culture of human fibroblasts on a collagenous carrier for gingival augmentation is an esthetic and effective method of mucogingival complex repair . The scaffolds were substituted and completely re-epithelialized within 12 weeks according to histologic results The aim of this study was to clinical ly evaluate the use of alloderm to increase the width of attached gingiva . Nine patients were selected . The inclusion criteria were : attached gingiva smaller than 1 mm ; Miller 's class I and II gingival recession ; patients able to attend control dental appointments ; absence of periodontal pocket and endodontic treatment in the neighboring area where the acellular dermal graft would be placed . The clinical evaluation included : allograft shrinkage 7 , 14 , 21 , 30 , 60 and 90 days after surgery ; width of attached gingiva at the end of the study ; difference in color and mobility of allograft . Allograft shrinkage was calculated by comparing its area immediately after surgery to its areas in the other days . Five st and ardized photographs were taken , digitized and the allograft area was measured . Paired Student 's t-test was used to compare the clinical data ( alpha=0.05 ) . The mean allograft shrinkage 90 days after surgery was 90.43 % and the mean width was 1.27 mm . Difference in color was observed in only 1 subject and no allograft mobility was detected . The results showed a large shrinkage of allograft 90 days after its insertion , raising doubts as to its validity for increasing the width of attached gingiva BACKGROUND The st and ard of care for increasing keratinized gingiva adjacent to teeth that do not require root coverage is the free gingival graft ( FGG ) . A pilot study indicated that the use of a living cellular construct ( LCC ) could be effective in this clinical scenario . METHODS A pivotal , multicenter , r and omized , within-patient , controlled , open-label trial was conducted ( N = 96 patients ) . After removing the mucosa and keratinized gingiva from the test site , either an LCC or FGG was applied . The primary efficacy endpoint was the ability of the LCC to regenerate ≥2 mm keratinized gingiva at 6 months . Secondary measures were the same color and texture as the adjacent tissue , a 1-mm width of keratinized gingiva at 6 months , patient treatment preference , surgical site sensitivity at 1 week , and patient-reported pain after 3 days . Safety was assessed by reports of adverse events . RESULTS At 6 months , the LCC regenerated ≥2 mm of keratinized gingiva in 95.3 % of patients ( 81 of 85 patients ; P < 0.001 versus a 50 % predefined st and ard ) . As expected , the FGG generated more keratinized gingiva than the LCC ( 4.57 ± 1.0 mm versus 3.2 ± 1.1 mm , respectively ) . The gingiva regenerated with the LCC matched the color and texture of the adjacent gingiva . All patients achieved ≥1 mm keratinized gingiva with the LCC treatment by 6 months , and more patients preferred treatment with the LCC than with the FGG . No difference in sensitivity or pain was noted between the treatments . The treatments were well tolerated , and reported adverse events were typical for this type of periodontal surgery . CONCLUSION The use of an LCC may provide a safe and effective therapy for augmenting the zone of keratinized gingiva BACKGROUND The st and ard of care for increasing keratinized tissue ( KT ) and vestibular area is an autogenous free gingival graft ( FGG ) and vestibuloplasty ; however , there is morbidity associated with the harvest of autogenous tissue , and supply is limited . The purpose of this study is to determine if a xenogeneic collagen matrix ( CM ) might be as effective as FGG . METHODS This study is a single-masked , r and omized , controlled , split-mouth study of 30 patients with insufficient zones of KT ( < 2 mm ) . It uses a within-patient treatment-comparison design to establish non-inferiority of the test ( CM ) versus control ( FGG ) therapy . The primary efficacy endpoint was change in KT width ( ∆KT ) from surgery to 6 months post-surgery . Secondary endpoints included traditional periodontal measures , such as clinical attachment level , recession , and bleeding on probing . Patient-reported pain , discomfort , and esthetic satisfaction were also recorded . Biopsies were obtained at 6 months . RESULTS Surgery and postoperative sequelae were uneventful , with normal healing observed at both test and control sites . The primary outcome , ∆KT width at 6 months , did not establish non-inferiority of CM compared to FGG ( P = 0.9992 ) , with the FGG sites averaging 1.5 mm more KT width than CM sites . However , the amount of new KT generated for both therapies averaged ≥2 mm . Secondary outcomes were not significantly different between test and control sites . All site biopsies appeared as normal mucoperiosteum with keratinized epithelium . CM sites achieved better texture and color matches , and more than two-thirds of patients preferred the appearance of their CM sites . CONCLUSION With the proviso of sufficient KT ( ≈2 mm in width ) and study goals of lower morbidity , unlimited supply , and patient satisfaction , CM appears to be a suitable substitute for FGG in vestibuloplasty procedures design ed to increase KT around teeth |
12,949 | 23,609,361 | The benefit of antineoplastic combined with whole brain radiation for brain metastases was not concerned , either in the brain metastases from unselected primary tumors or lung cancer | BACKGROUND The st and ard treatment for brain metastases is whole brain radiation , but the medium survival is about 3 - 10 months and had n't be improved for years .
AIM This study was to evaluate the effect of antineoplastic therapy combined with whole brain radiation for brain metastases . | PURPOSE Little progress has been made in the treatment of adult high- grade gliomas over the last two decades , thus necessitating a search for novel therapeutic strategies . Malignant gliomas are vascular or angiogenic tumors , which leads to the supposition that angiogenesis inhibition may represent a potentially promising strategy in the treatment of these tumors . We present the results of a phase II trial of thalidomide , a putative inhibitor of angiogenesis , in the treatment of adults with previously irradiated , recurrent high- grade gliomas . PATIENTS AND METHODS Patients with a histologic diagnosis of anaplastic mixed glioma , anaplastic astrocytoma , or glioblastoma multiforme who had radiographic demonstration of tumor progression after st and ard external-beam radiotherapy with or without chemotherapy were eligible . Patients were initially treated with thalidomide 800 mg/d with increases in dose by 200 mg/d every 2 weeks until a final daily dose of 1,200 mg was achieved . Patients were evaluated every 8 weeks for response by both clinical and radiographic criteria . RESULTS A total of 39 patients were accrued , with 36 patients being assessable for both toxicity and response . Thalidomide was well tolerated , with constipation and sedation being the major toxicities . One patient developed a grade 2 peripheral neuropathy after treatment with thalidomide for nearly a year . There were two objective radiographic partial responses ( 6 % ) , two minor responses ( 6 % ) , and 12 patients with stable disease ( 33 % ) . Eight patients were alive more than 1 year after starting thalidomide , although almost all with tumor progression . Changes in serum levels of basic fibroblastic growth factor ( bFGF ) were correlated with time to tumor progression and overall survival . CONCLUSION Thalidomide is a generally well-tolerated drug that may have antitumor activity in a minority of patients with recurrent high- grade gliomas . Future studies will better define the usefulness of thalidomide in newly diagnosed patients with malignant gliomas and in combination with radiotherapy and chemotherapy . Additionally , studies will be needed to confirm the potential utility of changes in serum bFGF as a marker of antiangiogenic activity and /or glioma growth |
12,950 | 31,192,137 | Conclusions : Folfox-4 regimen is likely to be the optimal chemotherapy for patients with advanced BTC and the predominant targeted therapy has n't achieved significant success currently .
XP and GS can be considered as alternatives for advanced BTC | Background : Although gemcitabine plus cisplatin ( GP ) is considered as st and ard chemotherapy for patients with advanced biliary tract cancer ( BTC ) , the optimal regimen remains unknown . | BACKGROUND Combination chemotherapy has shown benefit in the treatment of biliary cancer and further improvements might be achieved by the addition of a biological agent . We report here the effect of chemotherapy with the monoclonal EGFR antibody panitumumab as therapy for KRAS wild-type biliary cancer . PATIENTS AND METHODS Patients with advanced biliary tract cancer were r and omised ( 2:1 ) to receive cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 on day 1 and day 8/q3w with ( arm A ) or without panitumumab ( arm B ; 9 mg/kg BW , i.v q3w ) . The primary end-point was the evaluation of progression-free survival ( PFS ) at 6 months . Secondary end-points included objective response rate ( ORR ) , overall survival ( OS ) , and toxicity . In addition , a post hoc assessment of genetic alterations was performed . Finally , we performed a meta- analysis of trials with chemotherapy with and without EGFR antibodies . RESULTS Sixty-two patients were r and omised in arm A and 28 patients in arm B. Patients received 7 treatment cycles in median ( 1 - 35 ) with a median treatment duration of 4.7 months ( 141 days , 8 - 765 ) . PFS rate at 6 months was 54 % in patients treated with cisplatin/gemcitabine and panitumumab but was 73 % in patients treated with cisplatin/gemcitabine without antibody , respectively . Secondary end-points were an ORR of 45 % in treatment arm A compared with 39 % receiving treatment B and a median OS of 12.8 months ( arm A ) and of 20.1 months ( arm B ) , respectively . In contrast to the p53-status , genetic alterations in IDH1/2 were linked to a high response after chemotherapy and prolonged survival . In accordance with our results , the meta- analysis of 12 trials did not reveal a survival advantage for patients treated with EGFR antibodies compared with chemotherapy alone . CONCLUSIONS Panitumumab in combination with chemotherapy does not improve ORR , PFS and OS in patients with KRAS wild-type , advanced biliary cancer . Genetic profiling should be included in CCA trials to identify and vali date predictive and prognostic biomarkers . CLINICAL TRIALS NUMBER The trial was registered with NCT01320254 BACKGROUND Combination chemotherapy with gemcitabine and a platinum-based agent is regarded as a st and ard treatment for patients with advanced biliary-tract cancer . Results of phase 2 trials of single-agent erlotinib in biliary-tract cancer and of gemcitabine plus erlotinib in pancreatic cancer have shown modest benefits . Therefore , we aim ed to investigate the efficacy of gemcitabine and oxaliplatin plus erlotinib versus chemotherapy alone for advanced biliary-tract cancer . METHODS In this open label , r and omised , phase 3 trial , we r and omly assigned patients ( in a 1:1 ratio ) with metastatic biliary-tract cancer ( cholangiocarcinoma , gallbladder cancer , or ampulla of Vater cancer ) to receive either first-line treatment with chemotherapy alone ( gemcitabine 1000 mg/m(2 ) on day 1 and oxaliplatin 100 mg/m(2 ) on day 2 ) or chemotherapy plus erlotinib ( 100 mg daily ) . Treatment was repeated every 2 weeks until disease progression or unacceptable toxic effects . R and omisation was done central ly ( stratified by participating centre and presence of measurable lesion ) . The primary endpoint was progression-free survival . Analyses were by intention-to-treat . This study is registered with Clinical Trials.gov , number NCT01149122 . FINDINGS 133 patients were r and omly assigned to the chemotherapy alone group and 135 to the chemotherapy plus erlotinib group . The groups were balanced except for a higher proportion of patients with cholangiocarcinoma in the group given erlotinib than in the chemotherapy alone group ( 96 [ 71 % ] patients vs 84 [ 63 % ] ) . Median progression-free survival was 4·2 months ( 95 % CI 2·7 - 5·7 ) in the chemotherapy alone group and 5·8 months ( 95 % CI 4·6 - 7·0 ) in the chemotherapy plus erlotinib group ( hazard ratio [ HR ] 0·80 , 95 % CI 0·61 - 1·03 ; p=0·087 ) . Significantly more patients had an objective response in the chemotherapy plus erlotinib group than in the chemotherapy alone group ( 40 patients vs 21 patients ; p=0·005 ) , but median overall survival was the same in both groups ( 9·5 months [ 95 % CI 7·5 - 11·5 ] in the chemotherapy alone group and 9·5 months [ 7·6 - 11·4 ] in the chemotherapy plus erlotinib group ; HR 0·93 , 0·69 - 1·25 ; p=0·611 ) . All-cause deaths within 30 days of r and om assignment occurred in one ( 1 % ) of the patients in the chemotherapy alone group and in four ( 3 % ) of those in the chemotherapy plus erlotinib group . The most common grade 3 - 4 adverse event was febrile neutropenia ( eight [ 6 % ] patients in the chemotherapy alone group and six [ 4 % ] in the chemotherapy plus erlotinib group ) . No patient died of treatment-related causes during the study . Subgroup analyses by primary site of disease showed that for patients with cholangiocarcinoma , the addition of erlotinib to chemotherapy significantly prolonged median progression-free survival ( 5·9 months [ 95 % CI 4·7 - 7·1 ] for chemotherapy plus erlotinib vs 3·0 months [ 1·1 - 4·9 ] for chemotherapy alone ; HR 0·73 , 95 % CI 0·53 - 1·00 ; p=0·049 ) . INTERPRETATION Although no significant difference in progression-free survival was noted between groups , the addition of erlotinib to gemcitabine and oxaliplatin showed antitumour activity and might be a treatment option for patients with cholangiocarcinoma . FUNDING None Background A st and ard treatment for unresectable advanced-stage intrahepatic cholangiocarcinoma ( IHCC ) has not yet been established . Although neoadjuvant concurrent chemoradiotherapy ( CCRT ) and liver transplantation are associated with long-term survival in select patients , the outcomes of CCRT for advanced-stage unresectable IHCC remain unclear . The aim of our study was to evaluate the outcomes of CCRT in patients with unresectable advanced-stage IHCC . Methods We retrospectively review ed the records of all patients with unresectable advanced stage ( stage IVa or IVb ) IHCC who were pathologically diagnosed and treated at National Cancer Center , Korea , from June 2001 to March 2012 . Of the total of 92 patients , 25 ( 27.1 % ) received capecitabine plus cisplatin ( XP ) chemotherapy with external radiotherapy ( RT ) ( XP-CCRT group ) and 67 ( 72.8 % ) received XP chemotherapy alone ( XP group ) . The clinical characteristics and outcomes of the 2 groups were compared . Results The 92 patients comprised 72 male and 20 female patients , with a median age of 58 years ( range 26–78 years ) . The baseline clinical characteristics of the 2 groups were similar . Patients in the XP-CCRT group received a mean 44.7 Gy of RT and a mean 5.6 cycles of XP chemotherapy , whereas patients in the XP group received a mean 4.0 cycles . The disease control rate was higher in the XP-CCRT group than in the XP group , but the difference was not statistically significant ( 56.0 % vs. 41.5 % , p = 0.217 ) . Although neutropenia was significantly more frequent in the XP-CCRT than in the XP group ( 48 % vs. 9 % , p < 0.001 ) , the rates of other toxicities and > grade 3 toxicities did not differ . At a median follow-up of 5.3 months , PFS ( 4.3 vs. 1.9 months , p = 0.001 ) and OS ( 9.3 vs. 6.2 months , p = 0.048 ) were significantly longer in the XP-CCRT than in the XP group . Conclusions XP-CCRT was well tolerated and was associated with longer PFS and OS than XP chemotherapy alone in patients with unresectable advanced IHCC . Controlled r and omized trials are required to determine whether XP-CCRT is a primary treatment option for patients with unresectable advanced IHCC BACKGROUND / AIM Few clinical trials are available for advanced biliary tract carcinoma ( BTC ) . We conducted this r and omized phase II clinical trial to explore efficacy and safety of 5-fluorouracil/leucovorin ( 5-FU/LV - de Gramont ) or the same regimen plus oxaliplatin ( Folfox 4 ) as first-line treatment of advanced BTC . PATIENTS AND METHODS Primary endpoint was overall survival ( OS ) ; secondary endpoints were progression-free survival ( PFS ) , response and toxicity . RESULTS A total of 48 patients were enrolled , 23 in de Gramont arm and 25 in the Folfox arm . Disease control rate was 56.5 % for de Gramont vs. 72 % for Folfox . RR was 21.7 % for de Gramont arm and 28 % for Folfox arm ( p=0.12 ) . PFS was in favor of Folfox ( 5.2 vs. 2.8 months ; p=0.031 ) . OS was 7.5 and 13.0 months for de Gramont and Folfox arm respectively ( p=0.0010 ) . Toxicity was generally mild in both arms . CONCLUSION Folfox 4 could be considered a valid option as first-line treatment of BTC due to its efficacy and tolerability Background : A British r and omised study of gemcitabine plus cisplatin ( GC ) combination showed promising results in biliary tract cancer ( BTC ) patients . In our study , we evaluated the efficacy and safety of this combination compared with gemcitabine alone ( G ) in Japanese BTC patients . Methods : Overall , 84 advanced BTC patients were r and omised to either cisplatin 25 mg m−2 plus gemcitabine 1000 mg m−2 on days 1 , 8 of a 21-day cycle ( GC-arm ) , or single-agent gemcitabine 1000 mg m−2 on days 1 , 8 and 15 of a 28-day cycle ( G-arm ) . Treatments were repeated for at least 12 weeks until disease progression or unacceptable toxicity occurred , up to a maximum of 48 weeks . Results : A total of 83 patients were included in the analysis . For the GC and G-arms , respectively , the 1-year survival rate was 39.0 vs 31.0 % , median survival time 11.2 vs 7.7 months , median progression-free survival time 5.8 vs 3.7 months and overall response rate 19.5 vs 11.9 % . The most common grade 3 or 4 toxicities ( GC-arm/G-arm ) were neutropenia ( 56.1%/38.1 % ) , thrombocytopenia ( 39.0%/7.1 % ) , leukopenia ( 29.3%/19.0 % ) , haemoglobin decrease ( 36.6%/16.7 % ) and γ-GTP increase ( 29.3%/35.7 % ) . Conclusions : Gemcitabine plus cisplatin combination therapy was found to be effective and well tolerated , suggesting that it could also be a st and ard regimen for Japanese patients PURPOSE This study aim ed to establish an effective prognostic nomogram for intrahepatic cholangiocarcinoma ( ICC ) after partial hepatectomy . PATIENTS AND METHODS The nomogram was based on a retrospectively study on 367 patients who underwent partial hepatectomy for ICC at the Eastern Hepatobiliary Surgery Hospital from 2002 to 2007 . The predictive accuracy and discriminative ability of the nomogram were determined by concordance index ( C-index ) and calibration curve and compared with five currently used staging systems on ICC . The results were vali date d using bootstrap resampling and a prospect i ve study on 82 patients operated on from 2007 to 2008 at the same institution . RESULTS On multivariate analysis of the primary cohort , independent factors for survival were serum carcinoembryonic antigen , CA 19 - 9 , tumor diameter and number , vascular invasion , lymph node metastasis , direct invasion , and local extrahepatic metastasis , which were all selected into the nomogram . The calibration curve for probability of survival showed good agreement between prediction by nomogram and actual observation . The C-index of the nomogram for predicting survival was 0.74 ( 95 % CI , 0.71 to 0.77 ) , which was statistically higher than the C-index values of the following systems : American Joint Committee on Cancer ( AJCC ) seventh edition ( 0.65 ) , AJCC sixth edition ( 0.65 ) , Nathan ( 0.64 ) , Liver Cancer Study Group of Japan ( 0.64 ) , and Okabayashi ( 0.67 ; P < .001 for all ) . It was also higher ( 0.74 ) in predicting survival for the mass-forming type of ICC ( P < .001 ) . In the validation cohort , the nomogram discrimination was superior to the five other staging systems ( C-index : 0.75 v 0.60 to 0.63 ; P < .001 for all ) . CONCLUSION The proposed nomogram result ed in more-accurate prognostic prediction for patients with ICC after partial hepatectomy 4106 Background : There is no st and ard palliative chemotherapy regimen in biliary tract cancers ( BTC ) . Fluoropyrimidine or gemcitabine , with or without platinum , are most frequently used . The purpose of this prospect i ve multicenter phase II study was to evaluate the efficacy and safety of FOLFOX-6(5-FU/LV plus oxaliplatin ) combination chemotherapy in patients with advanced BTC . METHODS Eligible criteria included pathologically or cytologically confirmed biliary adenocarcinoma , unresectable or metastatic BTCs with at least one measurable lesion , no previous palliative chemotherapy , age ≥ 18 , performance status ≤ 2 , adequate organ function and no clinical ly significant cardiovascular disease . 89.8 % patients had metastatic disease . All patients received FOLFOX-6 ( oxaliplatin 85mg/m2 and folinic acid 400 mg/m2 on day 1 follwed by a 5-FU bolus 400 mg/m2 and 46-h infusion 2400 mg/m2 every 2 weeks ) until progression of disease or unacceptable toxicities . Tumor response was evaluated each after four treatment cycles using the RECIST . RESULTS 49 patients were enrolled in this phase II study from May 2008 to Aug 2010 . Medain age was 60.14 years ( range 35 - 80 ) , male/female=27/12 , ECOG performance status 0/1/2 = 23/21/5 . The primary tumor site was 14 patients in gallbladders , 28 patients in intrahepatic cholangiocarcinoma , and 7 patients in extrahepatic cholangiocarcinoma . 44 patients showed metastatic disease at baseline . Total chemotherapeutic cycles were 210 and 4.29 cycles were performed each person . Treatment related grade 3/4 toxicities included ( number of cycles ) diarrhea ( 2 ) , neutropenia ( 10 ) , neutropenic fever ( 2 ) , anemia ( 1 ) , thrombocytopenia ( 2 ) , nausea ( 1 ) and pneumonia ( 1 ) . Overall response rate was 16.3 % and overall disease control rate was 61.7 % . The median TTP was 3.83 months ( 95%CI , 3.45 - 5.68 months ) and the overall survival was 10.77 months ( 95%CI , 7.92 - 13.62 months ) . No treatment related deaths occurred during the study . CONCLUSIONS This results suggest that FOLFOX-6 would be an effective and well-tolerated chemotherapy regimen for Korean patients with advanced BTC Background The results of R and omized Controlled Trials ( RCTs ) on time-to-event outcomes that are usually reported are median time to events and Cox Hazard Ratio . These do not constitute the sufficient statistics required for meta- analysis or cost-effectiveness analysis , and their use in secondary analyses requires strong assumptions that may not have been adequately tested . In order to enhance the quality of secondary data analyses , we propose a method which derives from the published Kaplan Meier survival curves a close approximation to the original individual patient time-to-event data from which they were generated . Methods We develop an algorithm that maps from digitised curves back to KM data by finding numerical solutions to the inverted KM equations , using where available information on number of events and numbers at risk . The reproducibility and accuracy of survival probabilities , median survival times and hazard ratios based on reconstructed KM data was assessed by comparing published statistics ( survival probabilities , medians and hazard ratios ) with statistics based on repeated reconstructions by multiple observers . Results The validation exercise established there was no material systematic error and that there was a high degree of reproducibility for all statistics . Accuracy was excellent for survival probabilities and medians , for hazard ratios reasonable accuracy can only be obtained if at least numbers at risk or total number of events are reported . Conclusion The algorithm is a reliable tool for meta- analysis and cost-effectiveness analyses of RCTs reporting time-to-event data . It is recommended that all RCTs should report information on numbers at risk and total number of events alongside KM curves Although the combination of cisplatin and gemcitabine ( GEM ) is considered the st and ard first-line chemotherapy against unresectable hilar cholangiocarcinoma ( HC ) , its efficacy is discouraging . The present r and omized open-label clinical trial aim ed to evaluate the efficacy and safety of the GEM plus S-1 ( GEM-S-1 ) combination against unresectable HC . Twenty-five patients per group were r and omly assigned to receive GEM , S-1 or GEM-S-1 . Neutropenia ( 56 % ) and leukopenia ( 40 % ) were the most common chemotherapy-related toxicities in the GEM-S-1 group . Median overall survival ( OS ) in the GEM-S-1 , GEM and S-1 groups was 11 , 10 and 6 months , respectively . GEM plus S-1 significantly improved OS compared to S-1 monotherapy ( OR=0.68 ; 95%CI , 0.50–0.90 ; P=0.008 ) . Median progression-free survival ( PFS ) times in the GEM-S-1 , GEM and S-1 groups were 4.90 , 3.70 and 1.60 months , respectively . GEM plus S-1 significantly improved PFS compared to S-1 monotherapy ( OR=0.50 ; 95%CI , 0.27–0.91 ; P=0.024 ) . Response rates were 36 % , 24 % and 8 % in the GEM-S-1 , GEM and S-1 groups , respectively . A statistically significant difference was found in response rates between the gemcitabine-S-1 and S-1 groups ( 36 % vs 8 % , P=0.017 ) . Patients with CA19 - 9<466 U/ml were more responsive to chemotherapeutic agents than those with CA19 - 9≥571 U/ml ( 88.9 % vs 0 % , P<0.001 ) . We conclude that the combination of GEM plus S-1 provides a better OS , PFS and response rate than S-1 monotherapy , but it did not significantly differ from GEM monotherapy . ( ChiCTR-TRC-14004733 ) BACKGROUND The management of biliary tract cancers ( BTCs ) is complex due to limited data on the optimal therapeutic approach . This phase II multicenter study evaluated the efficacy and tolerability of v and etanib monotherapy compared with v and etanib plus gemcitabine or gemcitabine plus placebo in patients with advanced BTC . PATIENTS AND METHODS Patients were r and omized in a 1 : 1 : 1 ratio to three treatment groups : v and etanib 300 mg monotherapy ( V ) , v and etanib 100 mg plus gemcitabine ( V/G ) , gemcitabine plus placebo ( G/P ) . V and etanib ( 300 mg or 100 mg ) or placebo was given in single oral daily doses . Gemcitabine 1000 mg/m(2 ) was i.v . infused on day 1 and day 8 of each 21-day cycle . The primary end point was progression-free survival ( PFS ) . Secondary end points were : objective response rate ( ORR ) , disease control rate , overall survival , duration of response , performance status and safety outcomes . RESULTS A total of 173 patients ( mean age 63.6 years ) were recruited at 19 centers across Italy . Median ( 95 % confidence intervals ) PFS ( days ) were 105 ( 72 - 155 ) , 114 ( 91 - 193 ) and 148 ( 71 - 225 ) , respectively , for the V , V/G and G/P treatment groups , with no statistical difference among them ( P = 0.18 ) . No statistical difference between treatments was observed for secondary end points , except ORR , which slightly favored the V/G combination over other treatments . The proportion of patients reporting adverse events ( AEs ) was similar for the three groups ( 96.6 % in V arm , 91.4 % in the V/G arm and 89.3 % in the G/P arm ) . CONCLUSIONS V and etanib treatment did not improve PFS in patients with advanced BTC . The safety profile of v and etanib did not show any additional AEs or worsening of already known AEs . CLINICAL TRIAL NUMBER NCT00753675 Summary Background Cisplatin and gemcitabine is the st and ard first-line chemotherapy regimen for patients with advanced biliary tract cancer ; expression of VEGF and its receptors is associated with adverse outcomes . We aim ed to assess the effect of the addition of cediranib ( an oral inhibitor of VEGF receptor 1 , 2 , and 3 ) to cisplatin and gemcitabine on progression-free survival . Methods In this multicentre , placebo-controlled , r and omised phase 2 study , we recruited patients aged 18 years or older with histologically confirmed or cytologically confirmed advanced biliary tract cancer from hepatobiliary oncology referral centres in the UK . Patients were eligible if they had an ECOG performance status of 0–1 and an estimated life expectancy of longer than 3 months . Patients were given first-line cisplatin and gemcitabine chemotherapy ( 25 mg/m2 cisplatin and 1000 mg/m2 gemcitabine [ on days 1 and 8 every 21 days , for up to eight cycles ] ) with either 20 mg oral cediranib or placebo once a day until disease progression . We r and omly assigned patients ( 1:1 ) with a minimisation algorithm , incorporating the stratification factors : extent of disease , primary disease site , previous treatment , ECOG performance status , and centre . The primary endpoint was progression-free survival in the intention-to-treat population . This study is registered with Clinical Trials.gov , number NCT00939848 , and was closed on Sept 30 , 2014 ; results of the final analysis for the primary endpoint are presented . Findings Between April 5 , 2011 , and Sept 28 , 2012 , we enrolled 124 patients ( 62 in each group ) . With a median follow-up of 12·2 months ( IQR 7·3–18·5 ) , median progression-free survival was 8·0 months ( 95 % CI 6·5–9·3 ) in the cediranib group and 7·4 months ( 5·7–8·5 ) in the placebo group ( HR 0·93 , 80 % CI 0·74–1·19 , 95 % CI 0·65–1·35 ; p=0·72 ) . Patients who received cediranib had more grade 3–4 toxic effects than did patients who received placebo : hypertension ( 23 [ 37 % ] vs 13 [ 21 % ] ; p=0·05 ) , diarrhoea ( eight [ 13 % ] vs two [ 3 % ] ; p=0·05 ) ; platelet count decreased ( ten [ 16 % ] vs four [ 6 % ] ; p=0·09 ) , white blood cell decreased ( 15 [ 24 % ] vs seven [ 11 % ] ; p=0·06 ) and fatigue ( 16 [ 24 % ] vs seven [ 11 % ] ; p=0·04 ) . Interpretation Cediranib did not improve the progression-free survival of patients with advanced biliary tract cancer in combination with cisplatin and gemcitabine , which remains the st and ard of care . Although patients in the cediranib group had more adverse events , we recorded no unexpected toxic effects . The role of VEGF inhibition in addition to chemotherapy for patients with advanced biliary tract cancer remains investigational . Funding Cancer Research UK and AstraZeneca Pharmaceuticals BACKGROUND There is no established st and ard chemotherapy for patients with locally advanced or metastatic biliary tract cancer . We initially conducted a r and omized , phase 2 study involving 86 patients to compare cisplatin plus gemcitabine with gemcitabine alone . After we found an improvement in progression-free survival , the trial was extended to the phase 3 trial reported here . METHODS We r and omly assigned 410 patients with locally advanced or metastatic cholangiocarcinoma , gallbladder cancer , or ampullary cancer to receive either cisplatin ( 25 mg per square meter of body-surface area ) followed by gemcitabine ( 1000 mg per square meter on days 1 and 8 , every 3 weeks for eight cycles ) or gemcitabine alone ( 1000 mg per square meter on days 1 , 8 , and 15 , every 4 weeks for six cycles ) for up to 24 weeks . The primary end point was overall survival . RESULTS After a median follow-up of 8.2 months and 327 deaths , the median overall survival was 11.7 months among the 204 patients in the cisplatin-gemcitabine group and 8.1 months among the 206 patients in the gemcitabine group ( hazard ratio , 0.64 ; 95 % confidence interval , 0.52 to 0.80 ; P<0.001 ) . The median progression-free survival was 8.0 months in the cisplatin-gemcitabine group and 5.0 months in the gemcitabine-only group ( P<0.001 ) . In addition , the rate of tumor control among patients in the cisplatin-gemcitabine group was significantly increased ( 81.4 % vs. 71.8 % , P=0.049 ) . Adverse events were similar in the two groups , with the exception of more neutropenia in the cisplatin-gemcitabine group ; the number of neutropenia-associated infections was similar in the two groups . CONCLUSIONS As compared with gemcitabine alone , cisplatin plus gemcitabine was associated with a significant survival advantage without the addition of substantial toxicity . Cisplatin plus gemcitabine is an appropriate option for the treatment of patients with advanced biliary cancer . ( Clinical Trials.gov number , NCT00262769 . Purpose Gemcitabine-cisplatin combination chemotherapy has been regarded as st and ard regimen for advanced or metastatic biliary tract cancer ( BTC ) , based on the ABC-02 trial . To date , however , no studies have compared the efficacies of gemcitabine-platinum and fluoropyrimidine- platinum combination chemotherapy , even though fluoropyrimidine has been widely used as a backbone agent for gastrointestinal cancer . This study compared the efficacy and toxicities of gemcitabine-cisplatin ( GP ) and capecitabine-cisplatin ( XP ) combination chemotherapy for treatment of advanced BTC . Material s and Methods We examined 49 patients treated with GP and 44 patients treated with XP from October 2009 to July 2012 . All patients had unresectable BTC . The GP regimen comprised gemcitabine ( 1,000 mg/m2 , intravenously [ IV ] , days 1 and 8) and cisplatin ( 75 mg/m2 , IV , day 1 ) . The XP regimen comprised capecitabine ( 1,250 mg/m2 twice a day , peroral , days 1 - 14 ) and cisplatin ( 60 mg/m2 , IV , day 1 , every three weeks ) . We analyzed the response rate ( RR ) , time to progression ( TTP ) , overall survival ( OS ) , and toxicity . Results The RRs were 27.3 % and 6.1 % in the XP and GP arms , respectively . XP result ed in longer TTP ( 5.2 months vs. 3.6 months , p=0.016 ) , but OS was not statistically different ( 10.7 months vs. 8.6 months , p=0.365 ) . Both regimens result ed in grade 3 - 4 hematologic toxicities , but febrile neutropenia was not noted . Grade 3 - 4 asthenia , stomatitis , and h and -foot syndrome occurred more frequently in the XP arm . Conclusion XP result ed in a superior TTP and RR compared to GP for treatment of advanced BTC , with comparable toxicity . Conduct of prospect i ve large , r and omized trials to evaluate the possibility of XP as another st and ard therapy is warranted Purpose In order to confirm the impact of adding S-1 to gemcitabine , we conducted a r and omized phase II study to compare the combination therapy of gemcitabine plus S-1 to gemcitabine monotherapy in patients with advanced biliary tract cancer . Methods Sixty-two patients with advanced cholangiocarcinoma or gallbladder cancer were r and omized to either the combination therapy of gemcitabine and S-1 ( gemcitabine 1,000 mg/m2 on days 1 and 15 and S-1 40 mg/m2 b.i.d . on days 1–14 , repeated every 4 weeks ) or gemcitabine monotherapy ( gemcitabine 1,000 mg/m2 on days 1 , 8 , and 15 , repeated every 4 weeks ) . The primary endpoint of this study was response rate , and the regimen which showed the better response rate was selected as a c and i date of phase III study . Tumor response was assessed every two cycles using Response Evaluation Criteria in Solid Tumors criteria version 1.0 . Results The response rates of the combination therapy and the monotherapy were 20.0 and 9.4 % , respectively . The median time-to-progressions and overall survivals of these two treatments were nearly the same ( 5.6 vs. 4.3 months ; 8.9 vs. 9.2 months ) . Adverse events occurred more frequently in the combination arm . Conclusions The combination therapy of gemcitabine and S-1 showed the better response rate , but the superiority of this combination therapy was not clear in total . Because the st and ard of care changed to the combination therapy with gemcitabine and cisplatin during this study , it is difficult to select this combination therapy with a 4-week regimen as a c and i date of phase III study Biliary tract cancer ( BTC ) is a rare and lethal disease with few therapeutic options . Pre clinical data suggest that the epidermal growth factor receptor ( EGFR ) pathway could be involved in its progression Abstract Background . We evaluated the efficacy and safety of a combination of S-1 and cisplatin ( SP ) versus gemcitabine and cisplatin ( GP ) as first-line therapy for advanced biliary tract adenocarcinoma ( ABTA ) . Material and methods . Patients were r and omized to receive cisplatin ( 60 mg/m2 intravenously [ IV ] on Day 1 ) plus S-1 ( 40 mg/m2 bid orally on Days 1–14 ) or gemcitabine ( 1000 mg/m2 IV at 10 mg/m2/min on Days 1 and 8) every three weeks . The primary end point was six-month progression-free survival ( PFS ) . Results . Of 96 eligible patients , 49 were r and omized to GP and 47 to SP . At a median follow-up time of 14.2 months , the six-month PFS rates were 43.8 % and 34.7 % , respectively [ unadjusted HR ( GP/SP ) = 0.85 , 95 % CI 0.52–1.36 ] . The median OS values in the GP and SP groups were 10.1 months and 9.9 months , respectively [ unadjusted HR ( GP/SP ) = 0.72 , 95 % CI 0.45–1.17 ] . Grade 3 - 4 toxicities in the GP and SP groups included neutropenia ( 49.0 % vs. 31.8 % ) , anemia ( 22.4 % vs. 2.3 % ) , thrombocytopenia ( 22.4 % vs. 4.5 % ) , and asthenia ( 4.1 % vs. 2.1 % ) . Conclusion . Both GP and SP has comparable efficacy with favorable safety profile as first-line treatment for ABTA . ( Clinical Trials.gov number NCT 01375972 ) Abstract Purpose Gemcitabine/cisplatin combination therapy has been the st and ard palliative chemotherapy for patients with advanced biliary tract cancer ( BTC ) . We aim ed to evaluate the efficacy and safety of adding S-1 to gemcitabine/cisplatin combination therapy for patients with advanced BTC . Methods Patients with histologically or cytologically confirmed unresectable or recurrent BTC were eligible for inclusion . The primary end point was overall survival . Based on the results of our preceding phase I study , gemcitabine and cisplatin were administered intravenously at doses of 1,000 or 25 mg/m2 , respectively , on day 1 , and oral S-1 was administered daily at a dose of 80 mg/m2 on days 1–7 every 2 weeks . This study was registered with Clinical Trials.gov ( NCT01284413 ) and the UMIN Clinical Trials Registry ( ID 000004468 ) . Results Fifty patients enrolled between October 2011 and August 2012 were evaluated . After a median follow-up of 15.1 months ( range 2.4–24.4 months ) , the median overall survival time was 16.2 months [ 95 % confidence interval ( CI ) 10.2–22.2 months ] , and the one-year overall survival rate was 59.9 % ( 95 % CI 46.2–73.5 % ) . The grade 3–4 hematological toxicities were as follows : neutropenia ( 32 % ) , anemia ( 32 % ) , thrombocytopenia ( 10 % ) , and febrile neutropenia ( 4 % ) . The common grade 3–4 non-hematological toxicities were biliary tract infection ( 14 % ) , anorexia/nausea ( 10 % ) , and fatigue ( 8 % ) . Conclusions Gemcitabine/cisplatin/S-1 combination chemotherapy offered a promising survival benefit with manageable toxicity in patients with advanced BTC . A r and omized phase III trial to investigate the efficacy of this regimen compared to gemcitabine/cisplatin combination therapy in patients with advanced BTC is now underway ( UMIN000014371/NCT02182778 ) BACKGROUND Gemcitabine plus a platinum-based agent ( eg , cisplatin or oxaliplatin ) is the st and ard of care for advanced biliary cancers . We investigated the addition of cetuximab to chemotherapy in patients with advanced biliary cancers . METHODS In this non-comparative , open-label , r and omised phase 2 trial , we recruited patients with locally advanced ( non-resectable ) or metastatic cholangiocarcinoma , gallbladder carcinoma , or ampullary carcinoma and a WHO performance status of 0 or 1 from 18 hospitals across France and Germany . Eligible patients were r and omly assigned ( 1:1 ) central ly with a minimisation procedure to first-line treatment with gemcitabine ( 1000 mg/m(2 ) ) and oxaliplatin ( 100 mg/m(2 ) ) with or without cetuximab ( 500 mg/m(2 ) ) , repeated every 2 weeks until disease progression or unacceptable toxicity . R and omisation was stratified by centre , primary site of disease , disease stage , and previous treatment with curative intent or adjuvant therapy . Investigators who assessed treatment response were not masked to group assignment . The primary endpoint was the proportion of patients who were progression-free at 4 months , analysed by intention to treat . This study is registered with Clinical Trials.gov , number NCT00552149 . FINDINGS Between Oct 10 , 2007 , and Dec 18 , 2009 , 76 patients were assigned to chemotherapy plus cetuximab and 74 to chemotherapy alone . 48 ( 63 % ; 95 % CI 52 - 74 ) patients assigned to chemotherapy plus cetuximab and 40 ( 54 % ; 43 - 65 ) assigned to chemotherapy alone were progression-free at 4 months . Median progression-free survival was 6·1 months ( 95 % CI 5·1 - 7·6 ) in the chemotherapy plus cetuximab group and 5·5 months ( 3·7 - 6·6 ) in the chemotherapy alone group . Median overall survival was 11·0 months ( 9·1 - 13·7 ) in the chemotherapy plus cetuximab group and 12·4 months ( 8·6 - 16·0 ) in the chemotherapy alone group . The most common grade 3 - 4 adverse events were peripheral neuropathy ( in 18 [ 24 % ] of 76 patients who received chemotherapy plus cetuximab vs ten [ 15 % ] of 68 who received chemotherapy alone ) , neutropenia ( 17 [ 22 % ] vs 11 [ 16 % ] ) , and increased aminotransferase concentrations ( 17 [ 22 % ] vs ten [ 15 % ] ) . 70 serious adverse events were reported in 39 ( 51 % ) of 76 patients who received chemotherapy plus cetuximab ( 34 events in 19 [ 25 % ] patients were treatment-related ) , whereas 41 serious adverse events were reported in 25 ( 35 % ) of 71 patients who received chemotherapy alone ( 20 events in 12 [ 17 % ] patients were treatment-related ) . One patient died of atypical pneumonia related to treatment in the chemotherapy alone group . INTERPRETATION The addition of cetuximab to gemcitabine and oxaliplatin did not seem to enhance the activity of chemotherapy in patients with advanced biliary cancer , although it was well tolerated . Gemcitabine and platinum-based combination should remain the st and ard treatment option . FUNDING Institut National du Cancer , Merck Serono The oral fluoropyrimidine , S‐1 , combined with or without gemcitabine is considered to be a promising agent for treating advanced biliary tract cancer ; gemcitabine plus cisplatin is the current st and ard regimen . This r and omized phase II trial was design ed to evaluate the safety and efficacy of two regimens : gemcitabine plus S‐1 ( GS ) ( gemcitabine : 1000 mg/m2 , day 1 and day 8 ; S‐1 : 60 mg/m2 , twice daily on days 1–14 , repeated every 3 weeks ) ; and S‐1 ( 80 mg/m2 , days 1–28 , given orally twice daily for 4 weeks , followed by a 2‐week rest , repeated every 6 weeks ) . The regimen with a higher 1‐year survival would be selected for a subsequent phase III trial . Between February 2009 and April 2010 , 101 patients were r and omized . For the GS ( n = 51 ) and S‐1 ( n = 50 ) arms , the 1‐year survival was 52.9 % ( 95 % confidence interval , 38.5–65.5 ) and 40.0 % ( 95 % confidence interval , 26.5–53.1 ) , and the median survival times were 12.5 and 9.0 months , respectively . Grade 3/4 hematological toxicities were more frequent in the GS arm ( leucocytes 29.4 % , neutrophils 60.8 % , hemoglobin 11.8 % , platelets 11.8 % ) than in the S‐1 arm ( leucocytes 2.0 % , neutrophils 4.0 % , hemoglobin 4.0 % , platelets 4.0 % ) . Although two treatment‐related deaths occurred in the GS arm , all other grade 3/4 non‐hematological toxicities were reversible . In conclusion , GS was considered to be more promising and was selected as the test regimen for a subsequent phase III trial comparing GS with gemcitabine plus cisplatin combination therapy . This study was registered at the UMIN Clinical Trials Registry as UMIN 000001685 ( http://www.umin.ac.jp/ctr/index.htm ) Purpose To evaluate the efficacy and safety of gemcitabine and S-1 combination chemotherapy in patients with advanced biliary tract cancer . Methods Patients with a measurable lesion and no previous history of chemotherapy or radiotherapy were enrolled . Gemcitabine was administered intravenously at a dose of 1,000 mg/m2 over 30 min on day 1 and 15 , repeated every 4 weeks . S-1 was administered orally at a dose of 40 mg/m2 b.i.d . on days 1–14 . Tumor response was assessed every two cycles using Response Evaluation Criteria in Solid Tumors criteria . Results As much as 35 patients were enrolled between December 2006 and July 2008 ; 14 patients ( 40 % ) with gallbladder cancer and 14 ( 40 % ) with intrahepatic cholangiocarcinoma were included and 7 patients ( 20 % ) had received previous surgical resection . The overall response rate was 34.3 % and the overall disease control rate was 82.9 % . The median overall survival time was 11.6 months ( 95 % CI , 7.3–15.6 months ) , and the median time to progression was 5.9 months ( 95 % CI , 4.0–7.7 months ) . The grade 3/4 toxicities were leucopenia ( 23 % ) , neutropenia ( 34 % ) , anemia ( 20 % ) , thrombocytopenia ( 6 % ) and anorexia ( 3 % ) . Conclusions Gemcitabine and S-1 combination chemotherapy has promising efficacy and good tolerability in patients with advanced biliary tract cancer BACKGROUND Chemoradiotherapy ( CHRT ) is often advocated for locally-advanced biliary tract cancer ( LABTC ) . However there was not comparative study with chemotherapy alone ( CH ) . PATIENTS AND METHODS Patients with hilar or extrahepatic non-metastatic , LABTC could be included in this phase II trial . The inclusion criteria required World Health Organisation ( WHO ) performance status ⩽ 2 , bilirubinemia ⩽ 50 μM/L after biliary drainage if necessary , and possibility of external radiotherapy . Fluorouracil ( 5 FU ) infusion and cisplatin , were given in association to radiotherapy ( 50 Gy ) in the CHRT arm . Gemcitabine+oxaliplatin ( GEMOX ) was planned for 6 months in the CH arm . End-points were progression-free survival ( PFS ) , overall survival ( OS ) , toxicity and rate of biliary complications . RESULTS The trial was closed before completion due to slow recruitment . Eighteen and 16 patients were included in the CHRT and CH arms , respectively . Median follow up was 27.9 months ( ± 2.8 ) . Grade III-IV toxicities were mostly haematological ( 23 % and 25 % ) , and gastrointestinal ( 11 % and 6 % ) , in the CHRT and CH arm , respectively . Biliary complications occurred in 28 % of patients in the CHRT arm and 44 % of patients in the CH arm ( risk ratio ( RR ) : 1.60 [ 0.65 - 3.92 ] ) . Median PFS was 5.8 months in the CHRT group and 11.0 months in the CH group ( hazard ratio ( HR ) : 0.65 [ 0.32 - 1.33 ] ) . Median OS was 13.5 months in the CHRT group and 19.9 months in the CH group ( HR : 0.69 [ 0.31 - 1.55 ] ) . CONCLUSIONS Combination of gemcitabine plus cisplatin seems to be at least as efficient as chemoradiotherapy ( 50 Gy plus 5 FU and cisplatin ) in LABTC PURPOSE We design ed this study to evaluate efficacy of modified gemcitabine and oxaliplatin ( mGEMOX ) over best supportive care ( BSC ) or fluorouracil ( FU ) and folinic acid ( FA ) in unresectable gall bladder cancer ( GBC ) . PATIENTS AND METHODS Patients with unresectable GBC were enrolled for single center r and omized study . Arm A , BSC ; arm B , FU 425 mg/m(2 ) and FA 20 mg/m(2 ) intravenous ( IV ) bolus weekly for 30 weeks ( FUFA ) ; arm C , gemcitabine 900 mg/m(2 ) and oxaliplatin 80 mg/m(2 ) IV infusion on days 1 and 8 every 3 weeks for maximum of six cycles . Eighty-one patients were r and omly assigned , arms A ( n = 27 ) , B ( n = 28 ) , and C ( n = 26 ) . RESULTS Complete response plus partial response in the three groups was 0 ( 0 % ) , four ( 14.3 % ) , and eight ( 30.8 % ) respectively ( P < .001 ) . Two patients in the mGEMOX arm and one patient in the FUFA arm underwent curative resection after chemotherapy . One patient in the mGEMOX arm had complete pathologic response . Median overall survival ( OS ) was 4.5 , 4.6 , and 9.5 months for the BSC , FUFA , and mGEMOX arms ( P = .039 ) , respectively . Progression-free survival ( PFS ) was 2.8 , 3.5 , and 8.5 months for the three groups ( P < .001 ) . There was no difference in grade 3/4 toxicities in the chemotherapy arms except transaminitis , which was more prevalent in mGEMOX arm ( P = .04 ) . Two patients in the FUFA arm and 10 patients in the mGEMOX arm had grade 3 or 4 myelosuppression . Two patients in the mGEMOX group had neutropenic fever that resolved with antibiotics . CONCLUSION This r and omized controlled trial confirmed the efficacy of chemotherapy ( mGEMOX ) compared with BSC and FUFA in improving OS and PFS in unresectable GBC Trends in biliary tract cancer incidence rates have increased in Shanghai , China . These trends have coincided with economic and developmental growth , as well as a shift in dietary patterns to a more Westernized diet . To examine the effect of dietary changes on incident disease , we evaluated associations between diet and biliary tract cancers amongst men and women from a population -based case-control study in Shanghai , China . Biliary tract cancer cases were recruited from 42 collaborating hospitals in urban Shanghai , and population -based controls were r and omly selected from the Shanghai Household Registry . Food frequency question naire data were available for 225 gallbladder , 190 extrahepatic bile duct , and 68 ampulla of Vater cancer cases . A total of 39 food groups were created and examined for associations with biliary tract cancer . Interestingly , only four food groups demonstrated a suggested association with gallbladder , extrahepatic bile duct , or ampulla of Vater cancers . The allium food group , consisting of onions , garlic , and shallots showed an inverse association with gallbladder cancer ( OR : 0.81 , 95 % CI : 0.68–0.97 ) . Similar trends were seen in the food group containing seaweed and kelp ( OR : 0.79 , 95 % CI : 0.67–0.96 ) . In contrast , both preserved vegetables and salted meats food groups showed positive associations with gallbladder cancer ( OR:1.27 , 95 % CI : 1.06–1.52 ; OR : 1.18 , 95 % CI : 1.02–1.37 , respectively ) . Each of these four food groups showed similar trends for extrahepatic bile duct and ampulla of Vater cancers . The results of our analysis suggest intake of foods with greater anti-inflammatory properties may play a role in decreasing the risk of biliary tract cancers . Future studies should be done to better underst and effects of cultural changes on diet , and to further examine the impact diet and inflammation have on biliary tract cancer incidence & NA ; We evaluated the efficacy and toxicity of 5‐fluorouracil ( 5‐FU ) and folinic acid ( Mayo Clinic regimen ) in previously untreated patients with advanced gallbladder cancer . Thirty patients with histologically confirmed adenocarcinoma of gallbladder were enrolled on this trial . All were symptomatic and had stage IV disease . Patients received 5‐FU 425 mg/m2 daily for 5 consecutive days preceded by folinic acid 20 mg/m2/d . Treatment cycles were repeated every 28 days . Only two patients ( 7 % ) achieved an objective response to therapy . Another 10 ( 33 % ) had stable disease . Median time to progression was 4.7 months , and median overall survival was 14.8 months . Toxicity was moderate , and one treatment‐related death occurred . In conclusion , 5‐FU and folinic acid ( Mayo Clinic regimen ) is ineffective in the management of patients with advanced gallbladder cancer , and further trials with this regimen are not recommended Objectives : We conducted a retrospective cohort study to compare 2 different chemotherapy regimens for advanced biliary tract cancer ( BTC ) . Methods : Records of patients consecutively treated in our institution for advanced BTC from 2001 to 2006 were retrieved . Chemotherapy treatment with FOLFOX-4 regimen was routinely offered as first option ; gemcitabine ( GEM ) as single agent was proposed as an alternative option to patients who refused central venous catheter implantation . Toxicity , overall response rate , progression-free survival ( PFS ) , and overall survival ( OS ) obtained with the 2 treatments were evaluated . Results : Twenty-two patients were treated with FOLFOX-4 , whereas 18 patients received GEM . In the FOLFOX-4 group , the overall response rate was 13.6 % ( 95 % confidence interval [ CI ] , 4.7 - 33.3 ) , with 1 complete response and 2 partial responses , and 54.5 % ( 95 % CI , 34.7 - 73.1 ) of disease control rate ( complete response+partial response+stable disease ) . Median OS was 14.1 months ( 95 % CI , 9.1 - 18.8 ) and median PFS 5.44 months ( 95 % CI , 3.2 - 6.3 ) . In the GEM group , we observed no objective response , whereas 27.7 % ( 95 % CI , 12.5 - 50.9 ) obtained disease control . Median OS was 8.3 months ( 95 % CI , 4.7 - 12.9 ) and median PFS 3.9 months ( 95 % CI , 2.2 - 5.4 ) . Toxicity , mainly hematological , was acceptable for both treatments . On a multivariable Cox model including a propensity score , only the performance status and chemotherapy regimen were confirmed as strong predictors of OS , with an hazard ratio of 0.49 ( 95 % CI , 0.24 - 0.99 ) in favor of FOLFOX-4 . Conclusions : The combination chemotherapy with oxaliplatin and 5-fluorouracil is well tolerated and seems to provide prolonged survival than GEM alone in advanced BTC treatment , but further r and omized trials are warranted BACKGROUND Since sorafenib has shown activity in different tumour types and gemcitabine regimens improved the outcome for biliary tract cancer ( BTC ) patients , we evaluated first-line gemcitabine plus sorafenib in a double-blind phase II study . PATIENTS AND METHODS 102 unresectable or metastatic BTC patients with histologically proven adenocarcinoma of gallbladder or intrahepatic bile ducts , Eastern Cooperative Oncology Group ( ECOG ) 0 - 2 were r and omised to gemcitabine ( 1000 mg/m2 once weekly , first 7-weeks+1-week rest followed by once 3-weeks+1-week rest ) plus sorafenib ( 400 mg twice daily ) or placebo . Treatment continued until progression or unacceptable toxicity . Tumour sample s were prospect ively stained for sorafenib targets and potential biomarkers . Serum sample s ( first two cycles ) were measured for vascular endothelial growth factors ( VEGFs ) , vascular endothelial growth factor receptor 2 ( VEGFR-2 ) and stromal cell-derived factor 1 (SDF1)α by enzyme-linked immunosorbent assay ( ELISA ) . RESULTS Gemcitabine plus sorafenib was generally well tolerated . Four and three patients achieved partial responses in the sorafenib and placebo groups , respectively . There was no difference in the primary end-point , median progression-free survival ( PFS ) for gemcitabine plus sorafenib versus gemcitabine plus placebo ( 3.0 versus 4.9 months , P=0.859 ) , and no difference for median overall survival ( OS ) ( 8.4 versus 11.2 months , P=0.775 ) . Patients with liver metastasis after resection of primary BTC survived longer with sorafenib ( P=0.019 ) compared to placebo . Patients who developed h and -foot syndrome ( HFS ) showed longer PFS and OS than patients without HFS . Two sorafenib targets , VEGFR-2 and c-kit , were not expressed in BTC sample s. VEGFR-3 and Hif1α were associated with lymph node metastases and T stage . Absence of PDGFRβ expression correlated with longer PFS . CONCLUSION The addition of sorafenib to gemcitabine did not demonstrate improved efficacy in advanced BTC patients . Biomarker subgroup analysis suggested that some patients might benefit from combined treatment |
12,951 | 22,258,957 | There is insufficient evidence to guide selection of appropriate PEEP levels for RDS or CMV . | BACKGROUND Conventional mechanical ventilation ( CMV ) of neonates has been used as a treatment of respiratory failure for over 30 years .
While CMV facilitates gas exchange , it may simultaneously damage the lung .
Positive end expiratory pressure ( PEEP ) has received less attention than other ventilation parameters when considering this balance of benefit and possible harm .
While an appropriate level of PEEP may exert substantial benefits in ventilation , both inappropriately low or high levels may lead to harm .
An appropriate level of PEEP for neonates may also be best achieved by an individualized approach .
To compare the effects of different levels of PEEP in preterm newborn infants requiring CMV for respiratory distress syndrome (RDS).2 .
To compare the effects of different levels of PEEP in preterm infants requiring CMV for bronchopulmonary dysplasia (BPD).3 .
To compare the effects of different methods for individualizing PEEP to an optimal level in preterm newborn infants requiring CMV for RDS .
The study addressed the effects of different levels of PEEP in preterm newborn infants requiring CMV for RDS . | CONTEXT The need for lung protection is universally accepted , but the optimal level of positive end-expiratory pressure ( PEEP ) in patients with acute lung injury ( ALI ) or acute respiratory distress syndrome remains debated . OBJECTIVE To compare the effect on outcome of a strategy for setting PEEP aim ed at increasing alveolar recruitment while limiting hyperinflation to one aim ed at minimizing alveolar distension in patients with ALI . DESIGN , SETTING , AND PATIENTS A multicenter r and omized controlled trial of 767 adults ( mean [ SD ] age , 59.9 [ 15.4 ] years ) with ALI conducted in 37 intensive care units in France from September 2002 to December 2005 . INTERVENTION Tidal volume was set at 6 mL/kg of predicted body weight in both strategies . Patients were r and omly assigned to a moderate PEEP strategy ( 5 - 9 cm H(2)O ) ( minimal distension strategy ; n = 382 ) or to a level of PEEP set to reach a plateau pressure of 28 to 30 cm H(2)O ( increased recruitment strategy ; n = 385 ) . MAIN OUTCOME MEASURES The primary end point was mortality at 28 days . Secondary end points were hospital mortality at 60 days , ventilator-free days , and organ failure-free days at 28 days . RESULTS The 28-day mortality rate in the minimal distension group was 31.2 % ( n = 119 ) vs 27.8 % ( n = 107 ) in the increased recruitment group ( relative risk , 1.12 [ 95 % confidence interval , 0.90 - 1.40 ] ; P = .31 ) . The hospital mortality rate in the minimal distension group was 39.0 % ( n = 149 ) vs 35.4 % ( n = 136 ) in the increased recruitment group ( relative risk , 1.10 [ 95 % confidence interval , 0.92 - 1.32 ] ; P = .30 ) . The increased recruitment group compared with the minimal distension group had a higher median number of ventilator-free days ( 7 [ interquartile range { IQR } , 0 - 19 ] vs 3 [ IQR , 0 - 17 ] ; P = .04 ) and organ failure-free days ( 6 [ IQR , 0 - 18 ] vs 2 [ IQR , 0 - 16 ] ; P = .04 ) . This strategy also was associated with higher compliance values , better oxygenation , less use of adjunctive therapies , and larger fluid requirements . CONCLUSIONS A strategy for setting PEEP aim ed at increasing alveolar recruitment while limiting hyperinflation did not significantly reduce mortality . However , it did improve lung function and reduced the duration of mechanical ventilation and the duration of organ failure . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00188058 Twenty neonates requiring mechanical ventilation for respiratory failure , including 13 with hyaline membrane disease , were studied to assess the effects of alterations in ventilator setting s on mean airway pressure ( MAP ) , blood gases , and intracranial pressure ( ICP ) . The study involved r and om alterations in peak inspiratory pressure ( PIP ) , positive end-expiratory pressure ( PEEP ) , and inspiratory/expiratory ratio while MAP , PaO2 , ICP , and end-tibal PCO2 were continuously monitored . The results showed a significant relationship between MAP and PaO2 that was expressed as the change in PaO2 per millimeter of mercury change in MAP ( delta PaO2/delta MAP ) with a mean delta PaO2/delta MAP of 4.92 . The delta PaO2/delta MAP was highest for changes in PEEP ( 6.08 ) , followed by PIP ( 5.07 ) , and inspiratory/expiratory ratio ( 1.9 ) . There was a significant relationship between alterations in PEEP and PIP vs PaCO2 and pH. Increases in PEEP and decreases in PIP result ed in an elevated PaCO2 and a lowered pH , and decreases in PEEP and increases in PIP result ed in a decreased PaCO2 and an elevated pH. There was no significant relationship between MAP and ICP , but there was a significant association between delta ICP and delta PaCO2 during alterations in PIP ( r = .64 , P less than .001 ) . Increases in PEEP will lead to the greatest increase in PaO2 per change in MAP , followed by increase in PIP and inspiratory/expiratory ratio using a pressure-limited ventilator Abstract Positive end expiratory pressure is routinely used when ventilating preterm infants . Elevation of PEEP increases lung volume , as does surfactant treatment . The purpose of this study was to investigate the effect of various levels of PEEP within the range of 0.2 to 0.4 kPa on lung volume , compliance and gas exchange . We measured functional residual capacity , compliance of the respiratory system and arterial blood gases in 20 infants ( median birth weight 1240 g , range 660–1690 g ; median gestational age 28 weeks , range 24–32 weeks ; postnatal age 3–4 days ) . The infants were studied at 72 hours after their last dose of natural surfactant . At this time the patients were routinely nursed at 0.3 kPa of PEEP , the PEEP level was lowered to 0.2 kPa or raised to 0.4 kPa in r and om order . The PEEP level was then changed to the third level 0.4 kPa or 0.2 kPa . Each new setting was maintained for 20 min before FRC , compliance and blood gases were measured . FRC was assessed using SF6 washout technique . Increasing PEEP from 0.2 to 0.3 to 0.4 kPa result ed in increases in FRC ( p < 0.01 ) and oxygenation ( ns ) in all infants . In 16 infants compliance decreased and paCO2 increased with elevation of PEEP . Only in 4 infants compliance increased and CO2 fell . Conclusion : In the majority of our infants reduction of PEEP from 0.4 to 0.2 kPa result ed in increases in compliance and CO2 reduction . Our results might suggest that relatively low levels of PEEP < 0.3 kPa may be appropriate at 72 hours after surfactant replacement . Furthermore , these results underline the importance of PEEP test in clinical practice Sixteen rabbits were anaesthetized and subjected to saline lavage of the lungs to produce surfactant deficiency . This result ed in an arterial oxygen tension of less than 12 kPa on 100 % inspired oxygen and an inflection point on the pressure-volume curve at a pressure of 8–12 mmHg . After lavage the animals were r and omly assigned to receive either conventional mechanical ventilation ( CMV ) with a positive end-expiratory pressure ( PEEP ) of 1–2 mmHg ( group I —low PEEP ) or CMV with PEEP equal to the inflection point pressure ( group II — high PEEP ) . Mean airway pressures were kept at 14–16 mmHg in both groups by increasing the inspiratory : expiratory time ratios in the low PEEP group . The 5-h protocol was completed by 4 animals in group I and 6 animals in group II , early death usually being associated with a metabolic acidosis . On 100 % oxygen , the mean PaO2 at 2-h post-lavage was 15.2±8.3 kPa in group I and 39.6±21.8 kPa in group II . Group I had much lower end-expiratory lung volumes ( 3.0±1.5 ml above FRC ) than group II ( 34.9±12.2 ml above FRC ) . Histological examination of the lungs revealed significantly less hyaline membrane formation in group II ( p=0.001 ) . Thus , the prevention of alveolar collapse by the use of high PEEP levels appears to reduce lung damage in this preparation BACKGROUND There are limited data to inform the choice between early treatment with continuous positive airway pressure ( CPAP ) and early surfactant treatment as the initial support for extremely-low-birth-weight infants . METHODS We performed a r and omized , multicenter trial , with a 2-by-2 factorial design , involving infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation . Infants were r and omly assigned to intubation and surfactant treatment ( within 1 hour after birth ) or to CPAP treatment initiated in the delivery room , with subsequent use of a protocol -driven limited ventilation strategy . Infants were also r and omly assigned to one of two target ranges of oxygen saturation . The primary outcome was death or bronchopulmonary dysplasia as defined by the requirement for supplemental oxygen at 36 weeks ( with an attempt at withdrawal of supplemental oxygen in neonates who were receiving less than 30 % oxygen ) . RESULTS A total of 1316 infants were enrolled in the study . The rates of the primary outcome did not differ significantly between the CPAP group and the surfactant group ( 47.8 % and 51.0 % , respectively ; relative risk with CPAP , 0.95 ; 95 % confidence interval [ CI ] , 0.85 to 1.05 ) after adjustment for gestational age , center , and familial clustering . The results were similar when bronchopulmonary dysplasia was defined according to the need for any supplemental oxygen at 36 weeks ( rates of primary outcome , 48.7 % and 54.1 % , respectively ; relative risk with CPAP , 0.91 ; 95 % CI , 0.83 to 1.01 ) . Infants who received CPAP treatment , as compared with infants who received surfactant treatment , less frequently required intubation or postnatal corticosteroids for bronchopulmonary dysplasia ( P<0.001 ) , required fewer days of mechanical ventilation ( P=0.03 ) , and were more likely to be alive and free from the need for mechanical ventilation by day 7 ( P=0.01 ) . The rates of other adverse neonatal outcomes did not differ significantly between the two groups . CONCLUSIONS The results of this study support consideration of CPAP as an alternative to intubation and surfactant in preterm infants . ( Clinical Trials.gov number , NCT00233324 . A controlled trial of elective intervention with continuous inflating pressure ( CIP ) was performed in infants with severe hyaline membrane disease who weighed more than 1000 g at birth . Infants entered the trial if their arterial oxygen tension ( PaO2 ) fell below 60 mmHg while breathing a fractional inspired oxygen concentration ( F1O2 ) greater than 0 - 95 . 11 out of 12 infants in the CIP-treated group and 10 out of 12 in the control group survived . 7 treated and 6 control infants required mechanical ventilation . When CIP was started the Pao2 of the treated infants increased , and they breathed high concentrations of oxygen for a significantly shorter period than the control infants . During the 31-month duration of the trial 107 other infants with severe hyaline membrane disease were admitted who did not meet the criteria for entry to the trial . 37 survived after breathing high concentrations of oxygen ( F1O2 greater than 0 - 60 ) spontaneously without any ventilatory assistance , and the remaining 70 infants were already being ventilated on their arrival in the unit , usually because they had required mechanical ventilation during transfer from other hospitals . The neonatal survival rate for those infants born in this hospital during the study period was 88 % ( 50 out of 57 infants ) and for those referred from other hospitals it was 69 % ( 51 out of 74 infants ) . The maximum further increase in overall survival rate that might have been achieved in our population of infants if CIP had been initiated very early in the course of the illness was 5%--i.e . from 77 % ( 101/131 ) to 82 % ( 107/131 ) Objectives : To compare the effects of low vs. high tidal volume ( Vt ) with three positive end-expiratory pressure ( PEEP ) strategies on activated neutrophil influx into the lung . Design : Prospect i ve , r and omized controlled animal study . Setting : Animal laboratory in a university hospital . Subjects : Newborn piglets . Interventions : Surfactant-depleted piglets were r and omized in littermate pairs ; to PEEP of either 0 ( zero end-expiratory pressure [ ZEEP ] ; n = 6 ) , 8 cm H2O ( PEEP 8 ; n = 5 ) , or 1 cm H2O above the lower inflection point ( LIP ) ( PEEP > LIP ; n = 6 ) . Within each pair piglets were r and omized to a low Vt ( 5–7 mL/kg ) or high Vt strategy ( 17–19 mL/kg ) . After 4 hrs of mechanical ventilation , 18-fluorodeoxyglucose ( 18FDG ) was injected and positron emission tomography scanning was performed . Measurements and Main Results : Vt and PEEP changes on influx constants of 18FDG were assessed by analysis of variance . A within-litter comparison of Vt was nonsignificant ( p = .50 ) . A between-litter comparison , ordered in linear trend rank , from ZEEP , to PEEP 8 , to PEEP > LIP , showed a strong effect of PEEP on influx constant ( p = .019 ) . Conclusions : PEEP set above the LIP on the inspiratory limb of the pressure-volume curve affords a stronger lung protection than Vt strategy CONTEXT Low-tidal-volume ventilation reduces mortality in critically ill patients with acute lung injury and acute respiratory distress syndrome . Instituting additional strategies to open collapsed lung tissue may further reduce mortality . OBJECTIVE To compare an established low-tidal-volume ventilation strategy with an experimental strategy based on the original " open-lung approach , " combining low tidal volume , lung recruitment maneuvers , and high positive-end-expiratory pressure . DESIGN AND SETTING R and omized controlled trial with concealed allocation and blinded data analysis conducted between August 2000 and March 2006 in 30 intensive care units in Canada , Australia , and Saudi Arabia . PATIENTS Nine hundred eighty-three consecutive patients with acute lung injury and a ratio of arterial oxygen tension to inspired oxygen fraction not exceeding 250 . INTERVENTIONS The control strategy included target tidal volumes of 6 mL/kg of predicted body weight , plateau airway pressures not exceeding 30 cm H2O , and conventional levels of positive end-expiratory pressure ( n = 508 ) . The experimental strategy included target tidal volumes of 6 mL/kg of predicted body weight , plateau pressures not exceeding 40 cm H2O , recruitment maneuvers , and higher positive end-expiratory pressures ( n = 475 ) . MAIN OUTCOME MEASURE All-cause hospital mortality . RESULTS Eighty-five percent of the 983 study patients met criteria for acute respiratory distress syndrome at enrollment . Tidal volumes remained similar in the 2 groups , and mean positive end-expiratory pressures were 14.6 ( SD , 3.4 ) cm H2O in the experimental group vs 9.8 ( SD , 2.7 ) cm H2O among controls during the first 72 hours ( P < .001 ) . All-cause hospital mortality rates were 36.4 % and 40.4 % , respectively ( relative risk [ RR ] , 0.90 ; 95 % confidence interval [ CI ] , 0.77 - 1.05 ; P = .19 ) . Barotrauma rates were 11.2 % and 9.1 % ( RR , 1.21 ; 95 % CI , 0.83 - 1.75 ; P = .33 ) . The experimental group had lower rates of refractory hypoxemia ( 4.6 % vs 10.2 % ; RR , 0.54 ; 95 % CI , 0.34 - 0.86 ; P = .01 ) , death with refractory hypoxemia ( 4.2 % vs 8.9 % ; RR , 0.56 ; 95 % CI , 0.34 - 0.93 ; P = .03 ) , and previously defined eligible use of rescue therapies ( 5.1 % vs 9.3 % ; RR , 0.61 ; 95 % CI , 0.38 - 0.99 ; P = .045 ) . CONCLUSIONS For patients with acute lung injury and acute respiratory distress syndrome , a multifaceted protocol ized ventilation strategy design ed to recruit and open the lung result ed in no significant difference in all-cause hospital mortality or barotrauma compared with an established low-tidal-volume protocol ized ventilation strategy . This " open-lung " strategy did appear to improve secondary end points related to hypoxemia and use of rescue therapies . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00182195 Objective . Although earlier studies have suggested that early continuous airway positive pressure ( CPAP ) may be beneficial in reducing ventilator dependence and subsequent chronic lung disease in the extremely low birth weight ( ELBW ) infant , the time of initiation of CPAP has varied , and there are no prospect i ve studies of infants who have received CPAP or positive end-expiratory pressure ( PEEP ) from initial resuscitation in the delivery room ( DR ) . Current practice for the ELBW infant includes early intubation and the administration of prophylactic surfactant , often in the DR . The feasibility of initiating CPAP in the DR and continuing this therapy without intubation for surfactant has never been determined prospect ively in a population of ELBW infants . This study was design ed to determine the feasibility of r and omizing ELBW infants of < 28 weeks ’ gestation to CPAP/PEEP or no CPAP/PEEP during resuscitation immediately after delivery , avoiding routine DR intubation for surfactant administration , initiating CPAP on neonatal intensive care unit ( NICU ) admission , and assessing compliance with subsequent intubation criteria . Methods . Infants who were of < 28 weeks ’ gestation , who were born in 5 National Institute of Child Health and Human Development Neonatal Research Network NICUs from July 2002 to January 2003 , and for whom a decision had been made to provide full treatment after birth were r and omized to receive either CPAP/PEEP or not using a neonatal T-piece resuscitator ( NeoPuff ) . Infants would not be intubated for the sole purpose of surfactant administration in the DR . After admission to the NICU , all nonintubated infants were placed on CPAP and were to be intubated for surfactant administration only after meeting specific criteria : a fraction of inspired oxygen of > 0.3 with an oxygen saturation by pulse oximeter of < 90 % and /or an arterial oxygen pressure of < 45 mm Hg , an arterial partial pressure of carbon dioxide of > 55 mm Hg , or apnea requiring bag and mask ventilation . Results . A total of 104 infants were enrolled over a 6-month period : 55 CPAP and 49 control infants . No infant was intubated in the DR for the exclusive purpose of surfactant administration . Forty-seven infants were intubated for resuscitation in the DR : 27 of 55 CPAP infants and 20 of 49 control infants . Only 4 of the 43 infants who had a birth weight of < 700 g and 3 of the 37 infants of < 25 weeks ’ gestation were resuscitated successfully without positive pressure ventilation , and no difference was observed between the treatment groups . All infants of 23 weeks ’ gestation required intubation in the DR , irrespective of treatment group , whereas only 3 ( 14 % ) of 21 infants of 27 weeks ’ required such intubation . For infants who were not intubated in the DR , 36 infants ( 16 CPAP infants and 20 control infants ) were subsequently intubated in the NICU by day 7 , in accordance with the protocol . Overall , 80 % of studied infants required intubation within the first 7 days of life . The care provided for 52 ( 95 % ) of 55 CPAP infants and 43 ( 88 % ) of the 49 control infants was in compliance with the study protocol , with an overall compliance of 91 % . Conclusions . This study demonstrated that infants could be r and omized successfully to a DR intervention of CPAP/PEEP compared with no CPAP/PEEP , with intubation provided only for resuscitation indications , and subsequent intubation for prespecified criteria . Forty-five percent ( 47 of 104 ) of infants < 28 weeks ’ gestation required intubation for resuscitation in the DR . CPAP/PEEP in the DR did not affect the need for intubation at birth or during the subsequent week . Overall , 20 % of infants did not need intubation by 7 days of life . This experience should be helpful in facilitating the design of subsequent prospect i ve studies of ventilatory support in ELBW infants OBJECTIVE To compare immediate extubation versus delayed extubation after 36 hr in extremely low-birth weight infants receiving gentle mechanical ventilation and perinatal lung protective interventions . Our hypothesis was that a delayed extubation in this setting would decrease the rate of reintubation . STUDY DESIGN / METHODOLOGY : A prospect i ve , unmasked , r and omized , controlled trial to compare immediate extubation and delayed extubation after 36 hr . Optimized ventilation in both groups included continuous tracheal gas insufflation ( CTGI ) , prophylactic surfactant administration , low oxygen saturation target and moderate permissive hypercapnia . Successful extubation for at least 7 days was the primary criterion and ventilatory support requirements until 36 weeks gestational age the main secondary criteria . PATIENT SELECTION Eighty-six infants under 28 weeks gestational age in a single neonatal intensive tertiary care unit . RESULTS Delayed extubation ( 1.9 + /- 0.8 days vs. 0.5 + /- 0.7 days ) did not improve the rate of successful extubation but had no long-term adverse effects . CTGI and the lung protective strategy we describe result ed in a very gentle ventilation . The rate of survival without bronchopulmonary dysplasia ( BPD , defined as any respiratory support at 36 weeks gestational age ) was similar in the two groups and remarkably high for the global population ( 78 % ) and for the subgroup of infants < 1,000 g at birth ( 75 % ) . CONCLUSIONS Adding 36 hr of optimized mechanical ventilation before first extubation does not improve the rate of successful extubation but has no adverse effects CONTEXT Despite more than 2 decades of outcomes research after very preterm birth , clinicians remain uncertain about the extent to which neonatal morbidities predict poor long-term outcomes of extremely low-birth-weight ( ELBW ) infants . OBJECTIVE To determine the individual and combined prognostic effects of bronchopulmonary dysplasia ( BPD ) , ultrasonographic signs of brain injury , and severe retinopathy of prematurity ( ROP ) on 18-month outcomes of ELBW infants . DESIGN Inception cohort assembled for the Trial of Indomethacin Prophylaxis in Preterms ( TIPP ) . SETTING AND PARTICIPANTS A total of 910 infants with birth weights of 500 to 999 g who were admitted to 1 of 32 neonatal intensive care units in Canada , the United States , Australia , New Zeal and , and Hong Kong between 1996 and 1998 and who survived to a postmenstrual age of 36 weeks . MAIN OUTCOME MEASURES Combined end point of death or survival to 18 months with 1 or more of cerebral palsy , cognitive delay , severe hearing loss , and bilateral blindness . RESULTS Each of the neonatal morbidities was similarly and independently correlated with a poor 18-month outcome . Odds ratios were 2.4 ( 95 % confidence interval [ CI ] , 1.8 - 3.2 ) for BPD , 3.7 ( 95 % CI , 2.6 - 5.3 ) for brain injury , and 3.1 ( 95 % CI , 1.9 - 5.0 ) for severe ROP . In children who were free of BPD , brain injury , and severe ROP the rate of poor long-term outcomes was 18 % ( 95 % CI , 14%-22 % ) . Corresponding rates with any 1 , any 2 , and all 3 neonatal morbidities were 42 % ( 95 % CI , 37%-47 % ) , 62 % ( 95 % CI , 53%-70 % ) , and 88 % ( 64%-99 % ) , respectively . CONCLUSION In ELBW infants who survive to a postmenstrual age of 36 weeks , a simple count of 3 common neonatal morbidities strongly predicts the risk of later death or neurosensory impairment Abstract Positive end expiratory pressure ( PEEP ) is routinely used when ventilating preterm infants , and high levels are recommended in those with severe respiratory distress syndrome ( RDS ) . Elevation of PEEP increases lung volume , as does surfactant administration . We postulated that in surfactant-treated infants even modest PEEP levels could result in overdistension and ( CO2 ) retention . To test that hypothesis , lung volume , compliance and arterial blood gases were measured in eight preterm infants ( median gestational age 28 weeks , range 26–35 weeks ) at three PEEP levels . The infants , all with RDS , were studied at a median time of 18 h , ( range 12–68 h ) after their last dose of surfactant . Infants were routinely nursed at 3 cmH2O of PEEP , the PEEP level was then raised to 6 cmH2O or lowered to 0 cmH2O in r and om order . The new setting was maintained for 20 min ; the PEEP level was then changed to the third level ( 0 or 6 cmH2O ) again for 20 min . At the end of each 20-min period , lung volume , compliance and blood gases were measured . Lung volume was assessed by measuring functional residual capacity ( FRC ) using a helium dilution technique . Compliance was measured by relating the volume change from a positive pressure inflation maintained until no further volume change occurred to the pressure drop ( peak inflating pressure PEEP ) . Increasing PEEP from 0 to 3 cmH2O and particularly to 6 cmH2O result ed in increases in FRC ( P < 0.05 ) , oxygenation ( ns ) and paCO2 ( P < 0.02 ) . Specific compliance ( compliance/FRC ) ( P < 0.05 ) and pH ( P < 0.02 ) fell . Conclusion Following surfactant treatment , relatively low levels of positive end expiratory pressure ( ≤3 cmH2O ) may be appropriate The influence of continuous positive airway pressure ( CPAP ) and positive end-expiratory pressure ( PEEP ) on mortality and complication rates in severe hyaline membrane disease ( HMD ) was evaluated in a r and omized , prospect i ve study . Patients were admitted to the study if the Po2 was less than 50 mm Hg with FiO2 greater than 0.6 . Twenty-four patients in each of three weight groups were equally divided between treatment and control groups . The treatment regimen included CPAP ( 6 to 14 cm H2O ) for spontaneously breathing patients and PEEP for patients requiring mechanical ventilation for apnea or hypercapnia ( Pco2 greater than 65 mm Hg ) . Control patients received oxygen and were mechanically ventilated if they had apnea , hypercapnia , or Po2 less than 50 mm Hg with FiO2 greater than 0.8 . Oxygenation improved after the start of CPAP or PEEP ; however , Pco2 rose after CPAP was initiated . There was no significant difference between treatment and control groups in mortality , requirement for mechanical ventilation , or incidence of pulmonary sequelae . The incidence of pulmonary air-leak was increased with Peep . the findings suggest that CPAP and PEEP have not significantly altered the outcome of HMD BACKGROUND Bronchopulmonary dysplasia is associated with ventilation and oxygen treatment . This r and omized trial investigated whether nasal continuous positive airway pressure ( CPAP ) , rather than intubation and ventilation , shortly after birth would reduce the rate of death or bronchopulmonary dysplasia in very preterm infants . METHODS We r and omly assigned 610 infants who were born at 25-to-28-weeks ' gestation to CPAP or intubation and ventilation at 5 minutes after birth . We assessed outcomes at 28 days of age , at 36 weeks ' gestational age , and before discharge . RESULTS At 36 weeks ' gestational age , 33.9 % of 307 infants who were assigned to receive CPAP had died or had bronchopulmonary dysplasia , as compared with 38.9 % of 303 infants who were assigned to receive intubation ( odds ratio favoring CPAP , 0.80 ; 95 % confidence interval [ CI ] , 0.58 to 1.12 ; P=0.19 ) . At 28 days , there was a lower risk of death or need for oxygen therapy in the CPAP group than in the intubation group ( odds ratio , 0.63 ; 95 % CI , 0.46 to 0.88 ; P=0.006 ) . There was little difference in overall mortality . In the CPAP group , 46 % of infants were intubated during the first 5 days , and the use of surfactant was halved . The incidence of pneumothorax was 9 % in the CPAP group , as compared with 3 % in the intubation group ( P<0.001 ) . There were no other serious adverse events . The CPAP group had fewer days of ventilation . CONCLUSIONS In infants born at 25-to-28-weeks ' gestation , early nasal CPAP did not significantly reduce the rate of death or bronchopulmonary dysplasia , as compared with intubation . Even though the CPAP group had more incidences of pneumothorax , fewer infants received oxygen at 28 days , and they had fewer days of ventilation . ( Australian New Zeal and Clinical Trials Registry number , 12606000258550 . ) Objective We examined the hypothesis that injurious strategies of mechanical ventilation alter the expression and distribution within the lung of tumor necrosis factor-&agr ; and interleukin-6 that are both duration and ventilation strategy dependent . SubjectsMale Sprague Dawley rats . Interventions Lungs from rats were preserved immediately after death or were r and omized to ex vivo ventilation with either a ) noninjurious ventilation ; b ) high end-inspiratory lung volume with positive end-expiratory pressure ( PEEP ) ; c ) high end-inspiratory lung volume without PEEP ; or d ) intermediate lung distension without PEEP , for periods ranging from 30 mins to 3 hrs . Measurement and Main Results Changes in cytokines were assessed by in situ hybridization , immunocytochemistry , simultaneous in situ hybridization and immunocytochemistry , Northern analysis , and enzyme-linked immunosorbent assay . Whereas minimal expression of tumor necrosis factor-&agr ; and interleukin-6 mRNA was found in lungs subjected to noninjurious ventilation , the three injurious strategies result ed in a diffuse increase in expression of tumor necrosis factor-&agr ; and interleukin-6 . The principal cells involved were the bronchial , bronchiolar , and alveolar epithelium . The changes in tumor necrosis factor-&agr ; mRNA and protein expression were dependent on both duration of ventilation and the ventilation strategy used . Conclusions The vast pulmonary epithelium is a major contributor to ventilation-induced changes in cytokine production and may play an important role in the pathogenesis of lung injury and systemic sequelae in ventilated subjects Preterm infants need the achievement of adequate lung volume . Lung recruitment maneuver ( LRM ) is applied during high-frequency oscillatory ventilation . We investigated the effect of an LRM with positive end-expiratory pressure ( PEEP ) on oxygenation and outcomes in infants conventionally ventilated for respiratory distress syndrome ( RDS ) . Preterm infants in assisted controlled ventilation+volume guarantee for RDS after surfactant r and omly received an LRM ( group A ) or did not ( group B ) . LRM entailed increments of 0.2 cm H (2)O PEEP every 5 minutes , until fraction of inspired oxygen ( Fi O(2))=0.25 . Then PEEP was reduced and the lung volume was set on the deflation limb of the pressure/volume curve . When saturation of peripheral oxygen fell and Fi O(2 ) rose , we reincremented PEEP until Sp O(2 ) became stable . Group A ( N=10 ) and group B ( N=10 ) infants were similar : gestational age 25 ± 2 versus 25 ± 2 weeks ; body weight 747 ± 233 versus 737 ± 219 g ; clinical risk index for babies 9.8 versus 8.1 ; initial Fi O(2 ) 56 ± 24 versus 52 ± 21 , respectively . LRM began at 86 ± 69 minutes of age and lasted for 61 ± 18 minutes . Groups A and B showed different max PEEP during the first 12 hours of life ( 6.1 ± 0.3 versus 5.3 ± 0.3 cm H (2)O , P=0.00 ) , time to lowest Fi O(2 ) ( 94 ± 24 versus 435 ± 221 minutes ; P=0.000 ) and O(2 ) dependency ( 29 ± 12 versus 45 ± 17 days ; P=0.04 ) . No adverse events and no differences in the outcomes were observed . LRM led to the earlier lowest Fi O(2 ) of the first 12 hours of life and a shorter O ( 2 ) dependency BACKGROUND Most patients requiring mechanical ventilation for acute lung injury and the acute respiratory distress syndrome ( ARDS ) receive positive end-expiratory pressure ( PEEP ) of 5 to 12 cm of water . Higher PEEP levels may improve oxygenation and reduce ventilator-induced lung injury but may also cause circulatory depression and lung injury from overdistention . We conducted this trial to compare the effects of higher and lower PEEP levels on clinical outcomes in these patients . METHODS We r and omly assigned 549 patients with acute lung injury and ARDS to receive mechanical ventilation with either lower or higher PEEP levels , which were set according to different tables of predetermined combinations of PEEP and fraction of inspired oxygen . RESULTS Mean ( + /-SD ) PEEP values on days 1 through 4 were 8.3+/-3.2 cm of water in the lower-PEEP group and 13.2+/-3.5 cm of water in the higher-PEEP group ( P<0.001 ) . The rates of death before hospital discharge were 24.9 percent and 27.5 percent , respectively ( P=0.48 ; 95 percent confidence interval for the difference between groups , -10.0 to 4.7 percent ) . From day 1 to day 28 , breathing was unassisted for a mean of 14.5+/-10.4 days in the lower-PEEP group and 13.8+/-10.6 days in the higher-PEEP group ( P=0.50 ) . CONCLUSIONS These results suggest that in patients with acute lung injury and ARDS who receive mechanical ventilation with a tidal-volume goal of 6 ml per kilogram of predicted body weight and an end-inspiratory plateau-pressure limit of 30 cm of water , clinical outcomes are similar whether lower or higher PEEP levels are used BACKGROUND In patients with the acute respiratory distress syndrome , massive alveolar collapse and cyclic lung reopening and overdistention during mechanical ventilation may perpetuate alveolar injury . We determined whether a ventilatory strategy design ed to minimize such lung injuries could reduce not only pulmonary complications but also mortality at 28 days in patients with the acute respiratory distress syndrome . METHODS We r and omly assigned 53 patients with early acute respiratory distress syndrome ( including 28 described previously ) , all of whom were receiving identical hemodynamic and general support , to conventional or protective mechanical ventilation . Conventional ventilation was based on the strategy of maintaining the lowest positive end-expiratory pressure ( PEEP ) for acceptable oxygenation , with a tidal volume of 12 ml per kilogram of body weight and normal arterial carbon dioxide levels ( 35 to 38 mm Hg ) . Protective ventilation involved end-expiratory pressures above the lower inflection point on the static pressure-volume curve , a tidal volume of less than 6 ml per kilogram , driving pressures of less than 20 cm of water above the PEEP value , permissive hypercapnia , and preferential use of pressure-limited ventilatory modes . RESULTS After 28 days , 11 of 29 patients ( 38 percent ) in the protective-ventilation group had died , as compared with 17 of 24 ( 71 percent ) in the conventional-ventilation group ( P<0.001 ) . The rates of weaning from mechanical ventilation were 66 percent in the protective-ventilation group and 29 percent in the conventional-ventilation group ( P=0.005 ) : the rates of clinical barotrauma were 7 percent and 42 percent , respectively ( P=0.02 ) , despite the use of higher PEEP and mean airway pressures in the protective-ventilation group . The difference in survival to hospital discharge was not significant ; 13 of 29 patients ( 45 percent ) in the protective-ventilation group died in the hospital , as compared with 17 of 24 in the conventional-ventilation group ( 71 percent , P=0.37 ) . CONCLUSIONS As compared with conventional ventilation , the protective strategy was associated with improved survival at 28 days , a higher rate of weaning from mechanical ventilation , and a lower rate of barotrauma in patients with the acute respiratory distress syndrome . Protective ventilation was not associated with a higher rate of survival to hospital discharge |
12,952 | 20,434,167 | This review , however , suggests that cefepime therapy in pediatric patients is not associated with an increased risk of adverse outcomes | OBJECTIVES We systematic ally review ed clinical trials on the safety and efficacy of cefepime in pediatric patients in view of recent reports , which suggested that cefepime is associated with increased 30-day all-cause mortality rates . | OBJECTIVE To evaluate the therapeutic effects and safety of cefepime ( Maxipime ) and sulbactam/cefoperazone ( sulperazone ) on moderate and severe respiratory infection in children . METHODS Totally 100 children hospitalized for pneumonia were r and omized equally into 2 groups , namely group A with maxipime treatment at the dose of 50 mg/kg given intravenously twice daily , and group B with sulperazone treatment at 50 - 100 mg/kg given intravenously twice a day . The therapeutic effects and safety of both medications were observed . RESULTS In maxipime group , 44 of the 50 cases were cured with complete elimination of the symptoms and signs , and obvious therapeutic effect was achieved in 5 cases with significant improvement or resolution of the majority of symptoms and signs . One case failed to respond favorably to the treatment , with the overall efficacy rate of 98 % without incidence of adverse effects . In sulperazone group , 40 of the 50 cases were cured , 6 showed significant improvement , and 4 failed to respond to the treatment , with the rate of 92 % . One patient complained of rashes during sulperazone treatment , which disappeared the next day without sulperazone withdrawal . Significant difference was not noted between the groups ( chi(2)=2.43 , P>0.05 ) . CONCLUSIONS Both maxipime and sulperazon are effective and safe for application in children with moderate and severe respiratory infections 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 A prospect i ve , open-label , r and omized , comparative study in pediatric cancer patients was conducted to evaluate the efficacy and safety of cefepime and meropenem in the empiric therapy of febrile neutropenic patients . Febrile episodes were classified as microbiologically documented infection , clinical documented infection , or fever of unknown origin . Clinical response to therapy was classified as success or failure . In this period 37 children with solid tumors including lymphoma , 25 males , 12 females , had neutropenia on 65 occasions . Microbiologically documented infections occurred in 21 episodes ( 32.31 % ) . Frequency of positive bacteria isolated was higher than gram-negative bacteria . There was no infection-related death . There were no statistical differences between the cefepime and meropenem groups for duration of fever or neutropenia , response rate , and necessity for modification . Cefepime appears to be as effective and safe as meropenem for empiric treatment of febrile episodes in neutropenic pediatric cancer patients 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 Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists Abstract Multidrug-resistant organisms cause late-onset ventilator-associated pneumonia ( VAP ) . In a pilot , r and omized and controlled study , the efficacy and safety of cefepime , in late-onset VAP in infants , have now been evaluated in Malaysia . Thirty children aged < 1 year with late-onset VAP ( i.e. VAP occurring 5 or more days after intubation ) were r and omized to receive cefepime or , as a control , ceftazidime . The clinical responses and the microbiological clearance of tracheal aspirates were evaluated in each arm . Adverse events , if any , were monitored clinical ly and by blood tests . Ten of the 15 children given cefepime and five of the 15 given ceftazidime showed a satisfactory clinical response ( P<0.1 ) . Cefepime appeared significantly better at clearing polymicrobial infections from tracheal aspirates . There were no fatalities in the cefepime arm but three in ceftazidime ( P<0.1 ) . The mean ( S.E. ) duration s of antibiotic use were 9.4 ( 1.5 ) days for cefepime and 7.6 ( 1.0 ) days for ceftazidime ( P>0.05 ) . No serious adverse effects were observed in either arm . In conclusion , in late-onset VAP in infants , cefepime monotherapy appears to be at least as effective and safe as ceftazidime monotherapy , with better microbiological clearance The purpose of this study was to compare the efficacy , safety , and cost of piperacillin/tazobactam with cefepime monotherapy in children with febrile neutropenia . A prospect i ve r and omized study in children and adolescent with cancer was conducted . Patients were r and omly assigned to receive either 80 mg/kg piperacillin/10 mg/kg tazobactam every 6 h ( maximum 4.5 g/dose ) or cefepime 50 mg/kg every 8 h ( maximum 2 g/dose ) . Treatment modification was defined as all the changes in the empirical antimicrobials after the first 96 h. Overall treatment success was defined as cure of febrile episode with or without modification . Cost of hospitalization , antimicrobial drugs , and supportive therapy were calculated . Fifty febrile netropenic episodes ( 25 in the piperacillin/tazobactam group , 25 in the cefepime group ) in 27 pediatric cancer patients were evaluated . The groups were comparable in terms of age , gender , body weight , primary diagnosis , disease status , initial neutrophil count , and duration of neutropenia . Microbiologically and clinical ly documented infection rate was 46 % . There was no infection-related mortality in the study period . The treatment success of initial empirical therapy without modification was not different in the 2 groups ( 56 % in piperacillin/tazobactam group and 48 % in cefepime group ) . Anti-anaerobic drugs were added more frequently in the cefepime group . Duration of fever , neutropenia , treatment , and cost of therapy were not different in the treatment groups . Piperacillin/tazobactam monoterapy is as effective as cefepime monotherapy in febril neutropenia of pediatric cancer patients The efficacy , safety , and cost of cefepime and ceftazidime + amikacin as empirical therapy in children with febrile neutropenia is compared . A prospect i ve r and omized study in children with cancer was conducted . Patients were r and omly assigned to receive either cefepime 150 mg/kg/day or ceftazidime 150 mg/kg/day combined with amikacin 15 mg/kg/day . Treatment modification was defined as all the changes in the empirical antimicrobials after the first 72 h. Overall treatment success was defined as cure of febrile episode with or without modification . Costs of hospitalization , antimicrobial drugs , and supportive therapy were calculated . Fifty febrile netropenic episodes were evaluated . Infectious agents were microbiologically identified in 28 % of episodes . The incidence of gram-negative and gram-positive isolates was equal . Overall treatment success was 100 % and success of initial empirical therapy without modification was 52 and 40 % in the cefepime and cefepime + amikacin groups , respectively . The response rate after glycopeptides were added to the regimen was 64 and 52 % in the cefepime and cefepime + amikacin arms , respectively . Glycopeptide and antifungal drugs were added more frequently in the ceftazidime + amikacin group . Duration of fever , hospitalization , and antimicrobial drug administration were longer in the ceftazidime + amikacin arm . The costs of the antimicrobial drugs , hospitalization , and total cost were lower in the cefepime arm . Cefepime monotherapy is as effective as ceftazidime + amikacin combination in febrile neutropenia of pediatric cancer patients and must be preferred due to shorter defervescence of fever , shorter hospitalization , and lower therapy cost BACKGROUND Cefepime has been used in clinical therapeutic trials for meningitis , serious infection and febrile neutropenia , comprising more than 800 pediatric patients . This agent has also been used in patients 12 years of age and older with uncomplicated and complicated urinary tract infections including pyelonephritis , but not in younger patients . In this study the safety and efficacy of cefepime were compared with those of ceftazidime for treatment of pyelonephritis in pediatric patients younger than 12 years of age . METHODS Two hundred ninety-nine pediatric patients ( ages 1 month to 12 years ) with pyelonephritis ( 300 episodes ) were enrolled in a r and omized , open label , multicenter trial . Individual results were evaluated by a blinded committee of experts . Cefepime was compared with ceftazidime , both administered parenterally at 50 mg/kg every 8 h. Patients were to receive the assigned study drug until at least 48 h after becoming afebrile . The i.v . treatment was then to be continued or replaced by oral trimethoprimsulfamethoxazole for a maximum of 12 to 14 days . RESULTS The predominant causative pathogens were Escherichia coli , 88 % ; Proteus spp . , 6 % ; Pseudomonas aeruginosa , 2 % ; and Klebsiella spp . , 2 % . Bacteriologic eradication was achieved in 96 and 94 % of cefepime and ceftazidime patients , respectively , at the end of i.v . study drug treatment and was maintained in 94 and 91 % , respectively , at the end of total study therapy . After study therapy bacteriologic eradication was maintained after 4 to 6 weeks in 86 % of cefepime cases and in 83 % of ceftazidime cases . A satisfactory clinical response occurred in 98 and 96 % of cefepime and ceftazidime patients , respectively , at the end of i.v . treatment and in 93 % at the end of total study therapy in both treatment arms . Drug-related clinical adverse events occurred in 14 cefepime patients ( 91 % ) and in 10 ceftazidime patients ( 7 % ) . CONCLUSIONS Cefepime and ceftazidime are equally safe and efficacious treatment for pyelonephritis in pediatric patients Abstract Infection remains the major cause of morbidity and mortality in immuno-compromised children with malignancy . In addition , the economic impact of antibiotic treatment should always be evaluated , especially in developing countries . In our center between January 1998 and January 1999 , 73 children with hematological malignancies [ acute lymphoblastic leukemia ( ALL ) , acute myeloid leukemia ( AML ) ] ; 9 children with solid tumors ( rhabdomyosarcoma , neuroblas-toma ) had 87 febrile neutropenic episodes ( related to chemotherapy ) . These children were r and omized prospect ively into three treatment groups . The first group ( n : 28 ) received cefepime plus netilmicin , while the second group ( n : 29 ) was treated with ceftazidime plus amikacin and the third ( n : 30 ) with meropenem as monotherapy . The aim of the study was to compare the success rates and cost of fourth generation cephalosporin plus aminoglycoside and monotherapy of meropenem with ceftazidime plus amikacin , which is the st and ard therapy for febrile neutropenia . Microbiologically documented infections were 29.9 % , clinical ly documented infections were 9.2 % and 60.9 % of the febrile neutropenic episodes were considered to be FUO . Gram-positive microorganisms were the most commonly isolated agents from blood cultures [ MRSA ( Methicillin Resistant Staphylococcus aureus ) in 6 patients and MSSA ( Methicillin Sensitive Staphylococcus aureus ) in 4 patients ] . The success rates were 78.5 % , 79.3 % and 73.3 % for the 1st , 2nd and 3rd groups respectively . In 4 patients ( 4.5 % ) fever responded only to amphotericin-B therapy . There was no statistically significant difference between the three treatment regimens with respect to efficacy , safety and tolerance ( x2 test , p>0.05 ) , but while the third and fourth generation cephalosporins + aminoglycosides were comparable for cost , the monotherapy regimen was the most expensive . The main determining factors for the choice of treatment of febrile neutropenic children , especially in a developing country , are cost , presence of indwelling catheter and the bacterial flora of the unit , as well as efficacy |
12,953 | 25,994,247 | On subgroup analysis , there was no statistically significant difference between everolimus and temsirolimus in the risk of relevant adverse events .
CONCLUSIONS This meta- analysis demonstrated that regimens containing everolimus , temsirolimus or ridaforolimus for the treatment of solid tumors are associated with a significantly increased risk of all- grade and high- grade diarrhea and stomatitis . | BACKGROUND The authors performed a systematic review and meta- analysis of diarrhea and stomatitis associated with the use of everolimus , temsirolimus or ridaforolimus in patients with solid tumors . | PURPOSE The oral mammalian target of rapamycin inhibitor everolimus demonstrated promising efficacy in a phase II study of pretreated advanced gastric cancer . This international , double-blind , phase III study compared everolimus efficacy and safety with that of best supportive care ( BSC ) in previously treated advanced gastric cancer . PATIENTS AND METHODS Patients with advanced gastric cancer that progressed after one or two lines of systemic chemotherapy were r and omly assigned to everolimus 10 mg/d ( assignment schedule : 2:1 ) or matching placebo , both given with BSC . R and omization was stratified by previous chemotherapy lines ( one v two ) and region ( Asia v rest of the world [ ROW ] ) . Treatment continued until disease progression or intolerable toxicity . Primary end point was overall survival ( OS ) . Secondary end points included progression-free survival ( PFS ) , overall response rate , and safety . RESULTS Six hundred fifty-six patients ( median age , 62.0 years ; 73.6 % male ) were enrolled . Median OS was 5.4 months with everolimus and 4.3 months with placebo ( hazard ratio , 0.90 ; 95 % CI , 0.75 to 1.08 ; P = .124 ) . Median PFS was 1.7 months and 1.4 months in the everolimus and placebo arms , respectively ( hazard ratio , 0.66 ; 95 % CI , 0.56 to 0.78 ) . Common grade 3/4 adverse events included anemia , decreased appetite , and fatigue . The safety profile was similar in patients enrolled in Asia versus ROW . CONCLUSION Compared with BSC , everolimus did not significantly improve overall survival for advanced gastric cancer that progressed after one or two lines of previous systemic chemotherapy . The safety profile observed for everolimus was consistent with that observed for everolimus in other cancers OBJECTIVE We report the clinical features and management outcomes in 7 patients with everolimus-related stomatitis . STUDY DESIGN Fifteen women with hormone-receptor-positive advanced breast cancer receiving everolimus combined with exemestane were prospect ively evaluated to assess the development of stomatitis . Oral ulcers were diagnosed based on established criteria . RESULTS Seven patients developed stomatitis ( 46.6 % ) . All patients were treated with topical dexamethasone solution , while everolimus was temporarily discontinued in 4 patients . Stomatitis resolved within 1 - 2 weeks . Two of the 4 patients , who had interrupted everolimus , developed recurrent stomatitis following drug resume and everolimus was again discontinued and restarted after 2 weeks . To date , 5 patients receive everolimus in full dose . The 2 patients , who developed recurrent stomatitis , received a reduced dose . CONCLUSIONS Everolimus-related oral ulcers were frequent and led to dose modifications . Controlled trials , endorsing a consensus in terminology , are needed to evaluate measures on prevention and management of this unique toxicity BACKGROUND We tested the oral mammalian target of rapamycin ( mTOR ) inhibitor everolimus in addition to paclitaxel in patients with HER2-negative tumours not responding to initial neoadjuvant cytotoxic and anti-angiogenic treatment . METHODS Patients with primary HER2-negative tumours received four neoadjuvant cycles of epirubicin/cyclophosphamide ( EC ) with or without bevacizumab . Patients without clinical response were r and omised to receive weekly paclitaxel ( 80 mg/m(2 ) ) with or without everolimus ( 5 mg p.o . daily , after a step-wise dose-escalation starting from 2.5 mg bid ) for 12 weeks before surgery . To detect an increase in pathological complete response ( pCR ; ypT0 ypN0 ) from 5 % to 12.1 % ( odds ratio 2.62 ) 566 patients had to be recruited . The trial was stopped prematurely due to completion of accrual in the main study . FINDINGS Of 1948 patients initially starting neoadjuvant treatment 403 were r and omised . A total of 18 ( 4.6 % ) patients , 7 ( 3.6 % ) treated with paclitaxel and everolimus and 11 ( 5.6 % ) treated with paclitaxel alone had a pCR ( odds ratio 0.36 ( OR ) ( 95 % confidence interval ( CI ) , 0.24 - 1.6 ) p=0.34 ) . Overall response rate in breast and lymph nodes at surgery was 52.2 % after paclitaxel plus everolimus and 61.7 % after paclitaxel alone ( p=0.063 ) . Breast conserving treatment was performed in 54.4 % of patients with the combination treatment and 61.9 % with paclitaxel alone ( p=0.20 ) . Mucosal inflammation , thrombocytopenia , neutropenia , infection , and skin rash were more frequent when everolimus was added to paclitaxel . INTERPRETATION Neoadjuvant therapy with everolimus and paclitaxel for patients with HER2-negative disease unresponsive to EC with or without bevacizumab did not improve the pCR rate . Long-term outcome is awaited . FUNDING Novartis , Roche , and Sanofi-Aventis Anti-cancer agents that inhibit the mTOR pathway are associated with a number of unique toxicities , with one of the most significant and potentially dose-limiting being stomatitis . The objective of this study was to report the clinical features and management outcomes of a series of cancer patients who developed painful mTOR inhibitor-associated stomatitis ( mIAS ) . Seventeen cancer patients developed mIAS while being treated with everolimus- or ridaforolimus-containing protocol s at the Dana-Farber Cancer Institute and were referred to the oral medicine clinic for evaluation and management . Clinical characteristics , toxicity management , and outcomes were summarized . In addition , the frequency and rationale for dose reductions and therapy discontinuation were assessed . The median duration of mTOR inhibitor therapy was 80 days ( range 9 - 187 days ) . The median time to development of mouth ulcers was 10 days ( range 4 - 25 days ) . Five patients required protocol -directed dose reductions due to grade s 2 and 3 stomatitis and one patient discontinued cancer treatment due to mouth ulcers . Clinical improvement and pain relief was reported in 86.6 % of patients following topical , intralesional , or systemic corticosteroid therapy , with side effects limited to secondary c and idiasis ( n=2 ) . Mouth ulcers are a common and potentially dose limiting toxicity associated with the use of mTOR inhibitors in cancer treatment . This case series demonstrates that local and systemic corticosteroid therapy is an effective approach to managing patients with symptomatic mIAS . Prospect i ve studies are necessary to evaluate the effectiveness of treatment and prevention strategies with the ultimate goal of improving overall cancer treatment outcomes PURPOSE Cross-talk between the estrogen receptor ( ER ) and the phosphoinositide-3-kinase (PI3K)/Akt/mammalian target of rapamycin ( mTOR ) pathways is a mechanism of resistance to endocrine therapy , and blockade of both pathways enhances antitumor activity in pre clinical models . This study explored whether sensitivity to letrozole was enhanced with the oral mTOR inhibitor , everolimus ( RAD001 ) . PATIENTS AND METHODS Two hundred seventy postmenopausal women with operable ER-positive breast cancer were r and omly assigned to receive 4 months of neoadjuvant treatment with letrozole ( 2.5 mg/day ) and either everolimus ( 10 mg/day ) or placebo . The primary end point was clinical response by palpation . M and atory biopsies were obtained at baseline and after 2 weeks of treatment ( ie , day 15 ) . Sample s were assessed for PI3 K mutation status ( PIK3CA ) and for pharmacodynamic changes of Ki67 , phospho-S6 , cyclin D1 , and progesterone receptor ( PgR ) by immunohistochemistry . RESULTS Response rate by clinical palpation in the everolimus arm was higher than that with letrozole alone ( ie , placebo ; 68.1 % v 59.1 % ) , which was statistically significant at the preplanned , one-sided , alpha = 0.1 level ( P = .062 ) . Marked reductions in progesterone receptor and cyclin D1 expression occurred in both treatment arms , and dramatic downregulation of phospho-S6 occurred only in the everolimus arm . An antiproliferative response , as defined by a reduction in Ki67 expression to natural logarithm of percentage positive Ki67 of less than 1 at day 15 , occurred in 52 ( 57 % ) of 91 patients in the everolimus arm and in 25 ( 30 % ) of 82 patients in the placebo arm ( P < .01 ) . The safety profile was consistent with historical results of everolimus monotherapy ; grade s 3 to 4 adverse events occurred in 22.6 % of patients who received everolimus and in 3.8 % of patients who received placebo . CONCLUSION Everolimus significantly increased letrozole efficacy in neoadjuvant therapy of patients with ER-positive breast cancer BACKGROUND Interferon alfa is widely used for metastatic renal-cell carcinoma but has limited efficacy and tolerability . Temsirolimus , a specific inhibitor of the mammalian target of rapamycin kinase , may benefit patients with this disease . METHODS In this multicenter , phase 3 trial , we r and omly assigned 626 patients with previously untreated , poor-prognosis metastatic renal-cell carcinoma to receive 25 mg of intravenous temsirolimus weekly , 3 million U of interferon alfa ( with an increase to 18 million U ) subcutaneously three times weekly , or combination therapy with 15 mg of temsirolimus weekly plus 6 million U of interferon alfa three times weekly . The primary end point was overall survival in comparisons of the temsirolimus group and the combination-therapy group with the interferon group . RESULTS Patients who received temsirolimus alone had longer overall survival ( hazard ratio for death , 0.73 ; 95 % confidence interval [ CI ] , 0.58 to 0.92 ; P=0.008 ) and progression-free survival ( P<0.001 ) than did patients who received interferon alone . Overall survival in the combination-therapy group did not differ significantly from that in the interferon group ( hazard ratio , 0.96 ; 95 % CI , 0.76 to 1.20 ; P=0.70 ) . Median overall survival times in the interferon group , the temsirolimus group , and the combination-therapy group were 7.3 , 10.9 , and 8.4 months , respectively . Rash , peripheral edema , hyperglycemia , and hyperlipidemia were more common in the temsirolimus group , whereas asthenia was more common in the interferon group . There were fewer patients with serious adverse events in the temsirolimus group than in the interferon group ( P=0.02 ) . CONCLUSIONS As compared with interferon alfa , temsirolimus improved overall survival among patients with metastatic renal-cell carcinoma and a poor prognosis . The addition of temsirolimus to interferon did not improve survival . ( Clinical Trials.gov number , NCT00065468 [ Clinical Trials.gov ] . ) BACKGROUND Oral ulcers is a well-recognised adverse event ( AE ) of mTOR inhibitors . Paradoxically , little is known about its natural history , risk factors , and basic management . PATIENTS AND METHODS AEs of 79 patients prospect ively enrolled in 6 phase I-II studies testing everolimus were review ed . The following parameters were analysed : incidence , severity , duration and associated AE . The association between OU and everolimus dose , pharmacokinetics and the effectiveness of empiric treatments were explored . RESULTS OU , grade 3 - 4 OU , prolonged time under OU and RCOU ( recurrent and chronic oral ulcer ) were observed in 72 % 11 % , 30 % and 25 % patients , respectively . Patients with antecedent of prior chemotherapy , with PS 1 , or receiving everolimus in combination tended to present higher rates of prolonged time under OU and of grade 3 - 4 OU . As everolimus daily dose increased , the median time to OU was shorter , the median duration was longer and OU incidence tended to increase . Simultaneously , OU tended to be associated with higher everolimus exposure . None of the empiric treatments appeared effective against OU ( preventive or curative intent ) . CONCLUSION Everolimus-induced OU is a frequent , recurrent and sometimes harmful complication . A dose effect relationship is displayed . Its daily management remains challenging . OU represents a key issue in the compliance of mTOR inhibitors BACKGROUND Disease progression in patients with HER2-positive breast cancer receiving trastuzumab might be associated with activation of the PI3K/Akt/mTOR intracellular signalling pathway . We aim ed to assess whether the addition of the mTOR inhibitor everolimus to trastuzumab might restore sensitivity to trastuzumab . METHODS In this r and omised , double-blind , placebo-controlled , phase 3 trial , we recruited women with HER2-positive , trastuzumab-resistant , advanced breast carcinoma who had previously received taxane therapy . Eligible patients were r and omly assigned ( 1:1 ) using a central patient screening and r and omisation system to daily everolimus ( 5 mg/day ) plus weekly trastuzumab ( 2 mg/kg ) and vinorelbine ( 25 mg/m(2 ) ) or to placebo plus trastuzumab plus vinorelbine , in 3-week cycles , stratified by previous lapatinib use . The primary endpoint was progression-free survival ( PFS ) by local assessment in the intention-to-treat population . We report the final analysis for PFS ; overall survival follow-up is still in progress . This trial is registered with Clinical Trials.gov , number NCT01007942 . FINDINGS Between Oct 26 , 2009 , and May 23 , 2012 , 569 patients were r and omly assigned to everolimus ( n=284 ) or placebo ( n=285 ) . Median follow-up at the time of analysis was 20.2 months ( IQR 15.0 - 27.1 ) . Median PFS was 7.00 months ( 95 % CI 6.74 - 8.18 ) with everolimus and 5.78 months ( 5.49 - 6.90 ) with placebo ( hazard ratio 0.78 [ 95 % CI 0.65 - 0.95 ] ; p=0.0067 ) . The most common grade 3 - 4 adverse events were neutropenia ( 204 [ 73 % ] of 280 patients in the everolimus group vs 175 [ 62 % ] of 282 patients in the placebo group ) , leucopenia ( 106 [ 38 % ] vs 82 [ 29 % ] ) , anaemia ( 53 [ 19 % ] vs 17 [ 6 % ] ) , febrile neutropenia ( 44 [ 16 % ] vs ten [ 4 % ] ) , stomatitis ( 37 [ 13 % ] vs four [ 1 % ] ) , and fatigue ( 34 [ 12 % ] vs 11 [ 4 % ] ) . Serious adverse events were reported in 117 ( 42 % ) patients in the everolimus group and 55 ( 20 % ) in the placebo group ; two on-treatment deaths due to adverse events occurred in each group . INTERPRETATION The addition of everolimus to trastuzumab plus vinorelbine significantly prolongs PFS in patients with trastuzumab-resistant and taxane-pretreated , HER2-positive , advanced breast cancer . The clinical benefit should be considered in the context of the adverse event profile in this population BACKGROUND Angiomyolipomas are slow-growing tumours associated with constitutive activation of mammalian target of rapamycin ( mTOR ) , and are common in patients with tuberous sclerosis complex and sporadic lymphangioleiomyomatosis . The insidious growth of these tumours predisposes patients to serious complications including retroperitoneal haemorrhage and impaired renal function . Everolimus , a rapamycin derivative , inhibits the mTOR pathway by acting on the mTOR complex 1 . We compared the angiomyolipoma response rate on everolimus with placebo in patients with tuberous sclerosis or sporadic lymphanioleiomyomatosis-associated angiomyolipomata . METHODS In this double-blind , placebo-controlled , phase 3 trial , patients aged 18 years or older with at least one angiomyolipoma 3 cm or larger in its longest diameter ( defined by radiological assessment ) and a definite diagnosis of tuberous sclerosis or sporadic lymphangioleiomyomatosis were r and omly assigned , in a 2:1 fashion with the use of an interactive web response system , to receive oral everolimus 10 mg per day or placebo . The primary efficacy endpoint was the proportion of patients with confirmed angiomyolipoma response of at least a 50 % reduction in total volume of target angiomyolipomas relative to baseline . This study is registered with Clinical Trials.gov number NCT00790400 . RESULTS 118 patients ( median age 31·0 years ; IQR 18·0–61·0 ) from 24 centres in 11 countries were r and omly assigned to receive everolimus ( n=79 ) or placebo ( n=39 ) . At the data cutoff , double-blind treatment was ongoing for 98 patients ; two main reasons for discontination were disease progression ( nine placebo patients ) followed by adverse events ( two everolimus patients ; four placebo patients ) . The angiomyolipoma response rate was 42 % ( 33 of 79 [ 95 % CI 31–53 % ] ) for everolimus and 0 % ( 0 of 39 [ 0–9 % ] ) for placebo ( response rate difference 42 % [ 24–58 % ] ; one-sided Cochran-Mantel-Haenszel test p<0·0001 ) . The most common adverse events in the everolimus and placebo groups were stomatitis ( 48 % [ 38 of 79 ] , 8 % [ 3 of 39 ] , respectively ) , nasopharyngitis ( 24 % [ 19 of 79 ] and 31 % [ 12 of 39 ] ) , and acne-like skin lesions ( 22 % [ 17 of 79 ] and 5 % [ 2 of 39 ] ) . INTERPRETATION Everolimus reduced angiomyolipoma volume with an acceptable safety profile , suggesting it could be a potential treatment for angiomyolipomas associated with tuberous sclerosis . FUNDING Novartis Pharmaceuticals Everolimus is a valid therapeutic option for neuroendocrine tumors ( NETs ) ; however , data in a real-world setting outside regulatory trials are sparse . The aim of this study was to determine everolimus tolerability and efficacy , in relation to previous treatments , in a compassionate use program . A total of 169 patients with advanced progressive NETs treated with everolimus were enrolled , including 85 with pancreatic NETs ( pNETs ) and 84 with nonpancreatic NETs ( non-pNETs ) . Previous treatments included somatostatin analogs ( 92.9 % ) , peptide receptor radionuclide therapy ( PRRT ; 50.3 % ) , chemotherapy ( 49.7 % ) , and PRRT and chemotherapy ( 22.8 % ) . Overall , 85.2 % of patients experienced adverse events ( AEs ) , which were severe ( grade 3 - 4 ) in 46.1 % . The most frequent severe AEs were pneumonitis ( 8.3 % ) , thrombocytopenia ( 7.7 % ) , anemia ( 5.3 % ) , and renal failure ( 3.5 % ) . In patients previously treated with PRRT and chemotherapy , a 12-fold increased risk for severe toxicity was observed , with grade 3 - 4 AEs reported in 86.8 % ( vs. 34.3 % in other patients ) . In addition , 63.3 % of patients required temporarily everolimus discontinuation due to toxicity . Overall , 27.8 % of patients died during a median follow-up of 12 months . Median progression-free survival ( PFS ) and overall survival ( OS ) were 12 months and 32 months , respectively . Similar disease control rates , PFS , and OS were reported in pNETs and non-pNETs . In the real-world setting , everolimus is safe and effective for the treatment of NETs of different origins . Higher severe toxicity occurred in patients previously treated with systemic chemotherapy and PRRT . This finding prompts caution when using this drug in pretreated patients and raises the issue of planning for everolimus before PRRT and chemotherapy in the therapeutic algorithm for advanced NETs PURPOSE Chemotherapy-induced diarrhea ( CID ) is a relatively common adverse event in the treatment of patients with colorectal cancer . The LAR for Chemotherapy-Induced Diarrhea ( LARCID ) trial evaluated the efficacy and safety of long-acting release octreotide ( octreotide LAR ) for the prevention of CID in this population . PATIENTS AND METHODS Patients with colorectal cancer starting adjuvant or first-line treatment with a chemotherapy combination containing fluorouracil , capecitabine , and /or irinotecan were r and omly assigned to receive octreotide LAR 30 mg intramuscularly every 4 weeks ( experimental arm ) or the physician 's treatment of choice in case of diarrhea ( control arm ) . RESULTS A total of 139 patients were r and omly assigned , most of whom received fluorouracil- and oxaliplatin-containing chemotherapy regimens . The rate of diarrhea was 76.1 % in the experimental group ( n = 68 ) and 78.9 % in the control group ( n = 71 ) . Treatment with octreotide LAR did not prevent or reduce the severity of CID . Treatment choices for diarrhea management included loperamide in the majority of patients . No benefit from octreotide LAR was identified in terms of need for diarrhea treatment , opioids , or intravenous hydration or in the rate of hospitalization or quality of life . CONCLUSION This study could not prove the efficacy of octreotide LAR in the prevention of CID BACKGROUND Tuberous sclerosis complex is a genetic disorder leading to constitutive activation of mammalian target of rapamycin ( mTOR ) and growth of benign tumours in several organs . In the brain , growth of subependymal giant cell astrocytomas can cause life-threatening symptoms -- eg , hydrocephalus , requiring surgery . In an open-label , phase 1/2 study , the mTOR inhibitor everolimus substantially and significantly reduced the volume of subependymal giant cell astrocytomas . We assessed the efficacy and safety of everolimus in patients with subependymal giant cell astrocytomas associated with tuberous sclerosis complex . METHODS In this double-blind , placebo-controlled , phase 3 trial , patients ( aged 0 - 65 years ) in 24 centres in Australia , Belgium , Canada , Germany , the UK , Italy , the Netherl and s , Pol and , Russian Federation , and the USA were r and omly assigned , with an interactive internet-response system , in a 2:1 ratio to oral everolimus 4·5 mg/m(2 ) per day ( titrated to achieve blood trough concentrations of 5 - 15 ng/mL ) or placebo . Eligible patients had a definite diagnosis of tuberous sclerosis complex and at least one lesion with a diameter of 1 cm or greater , and either serial growth of a subependymal giant cell astrocytoma , a new lesion of 1 cm or greater , or new or worsening hydrocephalus . The primary endpoint was the proportion of patients with confirmed response -- ie , reduction in target volume of 50 % or greater relative to baseline in subependymal giant cell astrocytomas . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00789828 . FINDINGS 117 patients were r and omly assigned to everolimus ( n=78 ) or placebo ( n=39 ) . 27 ( 35 % ) patients in the everolimus group had at least 50 % reduction in the volume of subependymal giant cell astrocytomas versus none in the placebo group ( difference 35 % , 95 % CI 15 - 52 ; one-sided exact Cochran-Mantel-Haenszel test , p<0·0001 ) . Adverse events were mostly grade 1 or 2 ; no patients discontinued treatment because of adverse events . The most common adverse events were mouth ulceration ( 25 [ 32 % ] in the everolimus group vs two [ 5 % ] in the placebo group ) , stomatitis ( 24 [ 31 % ] vs eight [ 21 % ] ) , convulsion ( 18 [ 23 % ] vs ten [ 26 % ] ) , and pyrexia ( 17 [ 22 % ] vs six [ 15 % ] ) . INTERPRETATION These results support the use of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis . Additionally , everolimus might represent a disease-modifying treatment for other aspects of tuberous sclerosis . FUNDING Novartis Pharmaceuticals PURPOSE Evaluate the activity of everolimus ( RAD001 ) in combination with octreotide long-acting repeatable ( LAR ) in patients with advanced low- to intermediate- grade neuroendocrine tumors . METHODS Treatment consisted of RAD001 5 mg/d ( 30 patients ) or 10 mg/d ( 30 patients ) and octreotide LAR 30 mg every 28 days . Thirty carcinoid and 30 islet cell patients were enrolled . RESULTS Intent-to-treat response rate was 20 % . Per protocol , there were 13 with partial responses ( 22 % ) , 42 with stable disease ( SD ; 70 % ) , and five patients with progressive disease ( 8 % ) . Overall median progression-free survival ( PFS ) was 60 weeks . Median PFS for patients with known SD at entry was longer than for those who had progressive disease ( 74 v 50 weeks ; P < .01 ) . Median overall survival has not been reached . One- , 2- , and 3-year survival rates were 83 % , 81 % , and 78 % , respectively . Among 37 patients with elevated chromogranin A , 26 ( 70 % ) achieved normalization or more than 50 % reduction . Most common toxicity was mild aphthous ulceration . Grade 3/4 toxicities occurring in > or= 10 % of patients included hypophosphatemia ( 11 % ) , fatigue ( 11 % ) , and diarrhea ( 11 % ) . Treatment was associated with a dose-dependent rise in lactate dehydrogenase ( LDH ) . Those with lower than 109 U/L rise in LDH at week 4 had shorter PFS ( 38 v 69 weeks ; P = .01 ) . Treatment was also associated with a decrease in proliferation marker Ki-67 among patients who underwent optional paired pre- and post-treatment biopsy ( P = .04 ) . CONCLUSION RAD001 at 5 or 10 mg/d was well tolerated in combination with octreotide LAR , with promising antitumor activity . Confirmatory studies are ongoing IMPORTANCE Aside from the multikinase inhibitor sorafenib , there are no effective systemic therapies for the treatment of advanced hepatocellular carcinoma . OBJECTIVE To assess the efficacy of everolimus in patients with advanced hepatocellular carcinoma for whom sorafenib treatment failed . DESIGN , SETTING , AND PARTICIPANTS EVOLVE-1 was a r and omized , double-blind , phase 3 study conducted among 546 adults with Barcelona Clinic Liver Cancer stage B or C hepatocellular carcinoma and Child-Pugh A liver function whose disease progressed during or after sorafenib or who were intolerant of sorafenib . Patients were enrolled from 17 countries between May 2010 and March 2012 . R and omization was stratified by region ( Asia vs rest of world ) and macrovascular invasion ( present vs absent ) . INTERVENTIONS Everolimus , 7.5 mg/d , or matching placebo , both given in combination with best supportive care and continued until disease progression or intolerable toxicity . Per the 2:1 r and omization scheme , 362 patients were r and omized to the everolimus group and 184 patients to the placebo group . MAIN OUTCOMES AND MEASURES The primary end point was overall survival . Secondary end points included time to progression and the disease control rate ( the percentage of patients with a best overall response of complete or partial response or stable disease ) . RESULTS No significant difference in overall survival was seen between treatment groups , with 303 deaths ( 83.7 % ) in the everolimus group and 151 deaths ( 82.1 % ) in the placebo group ( hazard ratio [ HR ] , 1.05 ; 95 % CI , 0.86 - 1.27 ; P = .68 ; median overall survival , 7.6 months with everolimus , 7.3 months with placebo ) . Median time to progression with everolimus and placebo was 3.0 months and 2.6 months , respectively ( HR , 0.93 ; 95 % CI , 0.75 - 1.15 ) , and disease control rate was 56.1 % and 45.1 % , respectively ( P = .01 ) . The most common grade 3/4 adverse events for everolimus vs placebo were anemia ( 7.8 % vs 3.3 % , respectively ) , asthenia ( 7.8 % vs 5.5 % , respectively ) , and decreased appetite ( 6.1 % vs 0.5 % , respectively ) . No patients experienced hepatitis C viral flare . Based on central laboratory results , hepatitis B viral reactivation was experienced by 39 patients ( 29 everolimus , 10 placebo ) ; all cases were asymptomatic , but 3 everolimus recipients discontinued therapy . CONCLUSIONS AND RELEVANCE Everolimus did not improve overall survival in patients with advanced hepatocellular carcinoma whose disease progressed during or after receiving sorafenib or who were intolerant of sorafenib . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01035229 PURPOSE Temsirolimus , a specific inhibitor of the mammalian target of rapamycin kinase , has shown clinical activity in mantle cell lymphoma ( MCL ) . We evaluated two dose regimens of temsirolimus in comparison with investigator 's choice single-agent therapy in relapsed or refractory disease . PATIENTS AND METHODS In this multicenter , open-label , phase III study , 162 patients with relapsed or refractory MCL were r and omly assigned ( 1:1:1 ) to receive one of two temsirolimus regimens : 175 mg weekly for 3 weeks followed by either 75 mg ( 175/75-mg ) or 25 mg ( 175/25-mg ) weekly , or investigator 's choice therapy from prospect ively approved options . The primary end point was progression-free survival ( PFS ) by independent assessment . RESULTS Median PFS was 4.8 , 3.4 , and 1.9 months for the temsirolimus 175/75-mg , 175/25-mg , and investigator 's choice groups , respectively . Patients treated with temsirolimus 175/75-mg had significantly longer PFS than those treated with investigator 's choice therapy ( P = .0009 ; hazard ratio = 0.44 ) ; those treated with temsirolimus 175/25-mg showed a trend toward longer PFS ( P = .0618 ; hazard ratio = 0.65 ) . Objective response rate was significantly higher in the 175/75-mg group ( 22 % ) compared with the investigator 's choice group ( 2 % ; P = .0019 ) . Median overall survival for the temsirolimus 175/75-mg group and the investigator 's choice group was 12.8 months and 9.7 months , respectively ( P = .3519 ) . The most frequent grade 3 or 4 adverse events in the temsirolimus groups were thrombocytopenia , anemia , neutropenia , and asthenia . CONCLUSION Temsirolimus 175 mg weekly for 3 weeks followed by 75 mg weekly significantly improved PFS and objective response rate compared with investigator 's choice therapy in patients with relapsed or refractory MCL |
12,954 | 23,721,958 | The most common option for local salvage therapy after radical prostatectomy ( RP ) was radiation .
Options for local salvage therapy after primary radiation included RP , brachytherapy , and cryotherapy .
Radiation therapy ( RT ) after RP can provide durable prostate-specific antigen ( PSA ) responses in a sizeable percentage of men , especially when given early ( ie , PSA < 1 ng/ml ) .
The role of salvage treatment after RT is less clear | CONTEXT Despite excellent cancer control with the treatment of localized prostate cancer ( PCa ) , some men will experience a recurrence of disease .
The optimal management of recurrent disease remains uncertain .
OBJECTIVE To systematic ally review recent literature regarding management of biochemical recurrence after primary treatment for localized PCa . | OBJECTIVES Treatment failure after radical prostatectomy is most commonly heralded by an increase in serum prostate-specific antigen ( PSA ) to detectable levels . We evaluated the clinical utility of an ultrasensitive chemiluminescent PSA assay . METHODS We evaluated the assay in banked sera obtained from 170 men after radical prostatectomy . Controls consisted of 142 females , 29 men who had undergone cystoprostatectomy without evidence of prostate cancer , and 25 men without evidence of recurrent disease at least 5 years after prostatectomy for organ-confined disease . Lead time to diagnosis of recurrence was based on comparisons with the IMx or T and em E assays using a cutoff of 0.1 ng/mL ( 100 pg/mL ) . RESULTS The biologic level of detection of this assay is 8 pg/mL. Serum PSA levels were undetectable in 82.4 % of females , 86.2 % of the cystoprostatectomy patients , and 96 % of the radical prostatectomy controls . After radical prostatectomy , PSA levels were undetectable at last check in 104 of 168 ( 61.9 % ) men . In the 24 men with prostate cancer recurrence , the enhanced sensitivity of 8 pg/mL provided a mean lead time based on conservative calculations of 12.7 to 22.5 months over conventional assays . Thirty-four of the 41 men with detectable PSA levels and no evidence of disease recurrence had PSA levels of 30 pg/mL or less . CONCLUSIONS PSA levels are undetectable in most men who do not have recurrence of disease after radical prostatectomy . Low but detectable serum PSA levels less than or equal to 30 pg/mL can be produced by nonmalignant sources of PSA . PSA assays with enhanced sensitivity can detect recurrent prostate cancer with significant lead time over conventional assays Objectives In this study , we evaluate the outcomes of salvage cryotherapy for locally recurrent prostate cancer within the COLD ( cryo online data ) Registry . Furthermore , we assess the results of salvage cryotherapy ( with intermediate follow-up ) stratified by pre-treatment prostate-specific antigen ( PSA ) levels to determine which patients may best be suited for treatment . Methods The COLD registry was developed as a prospect i ve , central ly collected data base among patients undergoing salvage cryoablation for locally recurrent prostate cancer following primary prostate radiotherapy with curative intent . Of the patients undergoing salvage cryotherapy ( without neoadjuvant hormonal ablative therapy ) , complete medical records were available in 156 patients , with their mean follow-up being 3.8 years ( 0.9–12.7 years ) . The treatment outcomes of salvage cryotherapy were assessed using the Phoenix definition ( nadir PSA + 2 ng/ml ) of biochemical failure . Results Of our entire study population , the biochemical disease-free survival ( bDFS ) rates at 1 , 2 , and 3 years were 89.0 , 73.7 , and 66.7 % , respectively . Stratification of our patients into two subgroups is based on their pre-treatment total serum PSA values < 5 and ≥5 ng/ml , and bDFS rates at 3 years for these two subgroups were 78.3 and 52.9 % , respectively . A Kaplan – Meier analysis of bDFS stratified by these same pre-treatment PSA values revealed that the subset of patients with a PSA ≥ 5 ng/ml had statistically significant poorer bDFS rates ( P = 0.01 ) . Conclusions Salvage prostate cryotherapy is a potentially curative local salvage therapy . The importance of early referral when patients have a pre-treatment PSA < 5 ng/ml is essential to optimize treatment outcomes PURPOSE High intensity focused ultrasound for the treatment of primary prostate cancer is increasing in a subset of men seeking definitive treatment with reduced morbidity . We review outcomes in men undergoing salvage radical prostatectomy after failed whole gl and high intensity focused ultrasound . MATERIAL S AND METHODS Prospect i ve data were collected for men presenting with an increasing prostate specific antigen and biopsy proven prostate cancer after high intensity focused ultrasound from 2007 to 2010 who underwent salvage open radical prostatectomy with a 22-month median followup , including prostate specific antigen , prostate volume , pathology results , continence and erectile function . RESULTS Data for 15 men were available , including median age 64 years ( IQR 55 - 69 ) , Gleason score before high intensity focused ultrasound of 6 ( 8) , Gleason score 7 ( 7 ) , median cores positive 39 % ( IQR 17%-63 % ) and median prostate specific antigen 7 ng/ml ( IQR 5 - 8 ) . Whole gl and high intensity focused ultrasound achieved median nadir prostate specific antigen 1.1 ng/ml ( IQR 0.5 - 3.1 ) . Biopsy after high intensity focused ultrasound demonstrated Gleason score 6 ( in 3 patients ) , 7 ( 9 ) and 8/9 ( 3 ) , and 42 % ( IQR 25%-50 % ) cores positive and a median time from high intensity focused ultrasound to radical prostatectomy of 22 months ( IQR 7 - 26 ) . Perioperative morbidity was limited to 1 transfusion in a patient with a rectal injury . Pathologically extensive periprostatic fibrosis was found with persistent prostate cancer , as pT3 disease ( in 9 of 14 ) , Gleason scores 6 ( 2 ) , 7 ( 9 ) and 8 of 9 ( 4 ) , with focally positive margins in 3 of 11 ( pT3a ) . Postoperative prostate specific antigen was unrecordable in 14 of 15 patients with further treatment in 2 . Postoperative continence ( more than 12 months of followup ) yielded no pad use in 6 of 10 men with universally poor erectile function . CONCLUSIONS Radical prostatectomy as salvage is feasible for men in whom high intensity focused ultrasound failed , but with a higher morbidity than for primary surgery . Pathology results are alarming given the number of cases with extraprostatic extension yet early followup data suggest acceptable oncologic control . These results should be factored in when counseling men who wish to undergo primary high intensity focused ultrasound CONTEXT Biochemical disease recurrence after radical prostatectomy often prompts salvage radiotherapy , but no studies to date have had sufficient numbers of patients or follow-up to determine whether radiotherapy improves survival , and if so , the subgroup of men most likely to benefit . OBJECTIVES To quantify the relative improvement in prostate cancer-specific survival of salvage radiotherapy vs no therapy after biochemical recurrence following prostatectomy , and to identify subgroups for whom salvage treatment is most beneficial . DESIGN , SETTING , AND PATIENTS Retrospective analysis of a cohort of 635 US men undergoing prostatectomy from 1982 - 2004 , followed up through December 28 , 2007 , who experienced biochemical and /or local recurrence and received no salvage treatment ( n = 397 ) , salvage radiotherapy alone ( n = 160 ) , or salvage radiotherapy combined with hormonal therapy ( n = 78 ) . MAIN OUTCOME MEASURE Prostate cancer-specific survival defined from time of recurrence until death from disease . RESULTS With a median follow-up of 6 years after recurrence and 9 years after prostatectomy , 116 men ( 18 % ) died from prostate cancer , including 89 ( 22 % ) who received no salvage treatment , 18 ( 11 % ) who received salvage radiotherapy alone , and 9 ( 12 % ) who received salvage radiotherapy and hormonal therapy . Salvage radiotherapy alone was associated with a significant 3-fold increase in prostate cancer-specific survival relative to those who received no salvage treatment ( hazard ratio [ HR ] , 0.32 [ 95 % confidence interval { CI } , 0.19 - 0.54 ] ; P<.001 ) . Addition of hormonal therapy to salvage radiotherapy was not associated with any additional increase in prostate cancer-specific survival ( HR , 0.34 [ 95 % CI , 0.17 - 0.69 ] ; P = .003 ) . The increase in prostate cancer-specific survival associated with salvage radiotherapy was limited to men with a prostate-specific antigen doubling time of less than 6 months and remained after adjustment for pathological stage and other established prognostic factors . Salvage radiotherapy initiated more than 2 years after recurrence provided no significant increase in prostate cancer-specific survival . Men whose prostate-specific antigen level never became undetectable after salvage radiotherapy did not experience a significant increase in prostate cancer-specific survival . Salvage radiotherapy also was associated with a significant increase in overall survival . CONCLUSIONS Salvage radiotherapy administered within 2 years of biochemical recurrence was associated with a significant increase in prostate cancer-specific survival among men with a prostate-specific antigen doubling time of less than 6 months , independent of other prognostic features such as pathological stage or Gleason score . These preliminary findings should be vali date d in other setting s , and ultimately , in a r and omized controlled trial PURPOSE Hormonal therapy ( HT ) is the current mainstay of systemic treatment for prostate specific antigen ( PSA ) only recurrence ( PSAR ) , however , there is virtually no published literature comparing HT to observation in the clinical setting . The goal of this study was to examine the Department of Defense Center for Prostate Disease Research observational data base to compare clinical outcomes in men who experienced PSAR after radical prostatectomy by early versus delayed use of HT and by a risk stratified approach . MATERIAL S AND METHODS Of 5,382 men in the data base who underwent primary radical prostatectomy ( RP ) , 4,967 patients were treated in the PSA-era between 1988 and December 2002 . Of those patients 1,352 men who had PSAR ( PSA after surgery greater than 0.2 ng/ml ) and had postoperative followup greater than 6 months were used as the study cohort . These patients were further divided into an early HT group in which patients ( 355 ) received HT after PSA only recurrence but before clinical metastasis and a late HT group for patients ( 997 ) who received no HT before clinical metastasis or by current followup . The primary end point was the development of clinical metastases . Of the 1,352 patients with PSAR clinical metastases developed in 103 ( 7.6 % ) . Patients were also stratified by surgical Gleason sum , PSA doubling time and timing of recurrence . Univariate and multivariate Cox proportional hazard models were used to evaluate the effect of early and late HT on clinical outcome . RESULTS Early HT was associated with delayed clinical metastasis in patients with a pathological Gleason sum greater than 7 or PSA doubling time of 12 months or less ( Hazards ratio = 2.12 , p = 0.01 ) . However , in the overall cohort early HT did not impact clinical metastases . Race , age at RP and PSA at diagnosis had no effect on metastasis-free survival ( p > 0.05 ) . CONCLUSIONS The retrospective observational multicenter data base analysis demonstrated that early HT administered for PSAR after prior RP was an independent predictor of delayed clinical metastases only for high-risk cases at the current followup . Further study with longer followup and r and omized trials are needed to address this important issue RADICALS is a large , international r and omised controlled trial addressing two of the most important questions in postoperative management after radical prostatectomy : the timing of postoperative radiotherapy ( immediate vs early salvage ) and the duration of hormone therapy ( none vs short term vs long term ) used in addition to prostate bed radiotherapy . It has been funded by the Clinical Trials Awards Advisory Committee and will be run by the Medical Research Council Clinical Trials Unit , in collaboration with the National Cancer Institute of Canada Clinical Trials Group and the Trial Management Group . Additional international collaborative groups are also being invited to take part . RADICALS is an ambitious trial , aim ing to recruit over 4000 patients . Widespread support from the urological and oncological communities will be required . More information relating to this study is available from the Medical Research Council Clinical Trials Unit via : [email protected] . © 2007 The Royal College of Radiologists PURPOSE Salvage radical prostatectomy is associated with a higher complication rate than radical prostatectomy without prior radiotherapy but the magnitude of the increase is not well delineated . MATERIAL S AND METHODS A total of 3,458 consecutive patients underwent open radical prostatectomy and 98 underwent open salvage radical prostatectomy from January 1999 to June 2007 . Data were collected from prospect i ve surgical and institutional morbidity data bases , and retrospectively from billing records and medical records . Medical and surgical complications were captured , grade d by the modified Clavien classification and classified by time of onset . RESULTS Median followup after salvage radical prostatectomy and radical prostatectomy was 34.5 and 45.5 months , respectively . Patients with salvage had significantly higher median age , modified Charlson comorbidity score , clinical and pathological stage , and Gleason score . They were less likely to have organ confined disease and more likely to have seminal vesicle invasion and nodal metastasis . There was no significant difference in median operative time , blood loss or transfusion rate . The salvage group had a higher adjusted probability of medical and surgical complications , including urinary tract infection , bladder neck contracture , urinary retention , urinary fistula , abscess and rectal injury . Only 1 of 4 potent patients with salvage prostatectomy who underwent bilateral nerve sparing recovered erection adequate for intercourse . The 3-year actuarial recovery of continence was 30 % ( 95 % CI 19 - 41 ) . CONCLUSIONS Medical and surgical complications of prostatectomy are significantly increased in the setting of prior radiotherapy . Underst and ing the magnitude of this increased risk is important for patient counseling |
12,955 | 27,549,581 | However , there was no significant reduction in either the proportion of patients with medication discrepancies or the mean number of discrepancies per patient .
Conclusion Medication reconciliation supported by an electronic tool was able to minimize the incidence of medications with unintended discrepancy , mainly drug omissions . | Background Medication reconciliation has been identified as an important intervention to minimize the incidence of unintentional medication discrepancies at transitions in care .
However , there is a lack of evidence for the impact of information technology on the rate and incidence of medication discrepancies identified during care transitions .
This systematic review was thus , aim ed to evaluate the impact of electronic medication reconciliation interventions on the occurrence of medication discrepancies at hospital transitions . | OBJECTIVES To study the feasibility and effectiveness of a discharge planning intervention . DESIGN Quasi-experimental pre-post study design . SETTING General medicine wards at three hospitals : an academic medical center , a community teaching hospital , and a community-based nonteaching hospital . PARTICIPANTS All patients aged 65 and older admitted to the hospitalist services . INTERVENTION The intervention toolkit had five core elements : admission form with geriatric cues , facsimile to the primary care provider , interdisciplinary worksheet to identify barriers to discharge , pharmacist-physician collaborative medication reconciliation , and predischarge planning appointments . MEASUREMENTS Thirty-day readmission and return to emergency department rates and patient satisfaction with discharge . Odds ratios were determined , and site effects were examined accordig to interaction terms and Breslow Day statistics . RESULTS Two hundred thirty-seven patients were followed during the preintervention period , and 185 were exposed to the intervention . Patients characteristics were similar across the two time periods . The proportion of patients with high- quality transitions home , measured according to Coleman 's Care Transition Measures , increased from 68 % to 89 % ( odds ratio (OR)=3.49 , 95 % confidence interval (CI)=2.06 - 5.92 ) . Return to the emergency department within 3 days of discharge was lower in the intervention period ( 10 % vs 3 % , OR=0.25 , 95 % CI=0.10 - 0.62 ) . At 30 days , there was a lower rate of readmission ( 22 % vs 14 % , OR=0.59 , 95 % CI=0.34 - 0.97 ) and fewer visits to the emergency department ( 21 % vs 14 % , OR=0.61 , 95 % CI=0.36 - 1.03 ) ( P=.06 ) . CONCLUSION When hospitalized elderly patients are treated with consideration of their specific needs , healthcare outcomes can be improved 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 BACKGROUND Prior studies suggest that unintended medication discrepancies that represent errors are common at the time of hospital admission . These errors are particularly worthy of attention because they are not likely to be detected by computerized physician order entry systems . METHODS We prospect ively studied patients reporting the use of at least 4 regular prescription medications who were admitted to general internal medicine clinical teaching units . The primary outcome was unintended discrepancies ( errors ) between the physicians ' admission medication orders and a comprehensive medication history obtained through interview . We also evaluated the potential seriousness of these discrepancies . All discrepancies were review ed with the medical team to determine if they were intentional or unintentional . All unintended discrepancies were rated for their potential to cause patient harm . RESULTS After screening 523 admissions , 151 patients were enrolled based on the inclusion criteria . Eighty-one patients ( 53.6 % ; 95 % confidence interval , 45.7%-61.6 % ) had at least 1 unintended discrepancy . The most common error ( 46.4 % ) was omission of a regularly used medication . Most ( 61.4 % ) of the discrepancies were judged to have no potential to cause serious harm . However , 38.6 % of the discrepancies had the potential to cause moderate to severe discomfort or clinical deterioration . CONCLUSIONS Medication errors at the time of hospital admission are common , and some have the potential to cause harm . Better methods of ensuring an accurate medication history at the time of hospital admission are needed BACKGROUND Clinical ly important medication errors are common after hospital discharge . They include preventable or ameliorable adverse drug events ( ADEs ) , as well as medication discrepancies or nonadherence with high potential for future harm ( potential ADEs ) . OBJECTIVE To determine the effect of a tailored intervention on the occurrence of clinical ly important medication errors after hospital discharge . DESIGN R and omized , controlled trial with concealed allocation and blinded outcome assessors . ( Clinical Trials.gov registration number : NCT00632021 ) SETTING Two tertiary care academic hospitals . PATIENTS Adults hospitalized with acute coronary syndromes or acute decompensated heart failure . INTERVENTION Pharmacist-assisted medication reconciliation , inpatient pharmacist counseling , low-literacy adherence aids , and individualized telephone follow-up after discharge . MEASUREMENTS The primary outcome was the number of clinical ly important medication errors per patient during the first 30 days after hospital discharge . Secondary outcomes included preventable or ameliorable ADEs , as well as potential ADEs . RESULTS Among 851 participants , 432 ( 50.8 % ) had 1 or more clinical ly important medication errors ; 22.9 % of such errors were judged to be serious and 1.8 % life-threatening . Adverse drug events occurred in 258 patients ( 30.3 % ) and potential ADEs in 253 patients ( 29.7 % ) . The intervention did not significantly alter the per-patient number of clinical ly important medication errors ( unadjusted incidence rate ratio , 0.92 [ 95 % CI , 0.77 to 1.10 ] ) or ADEs ( unadjusted incidence rate ratio , 1.09 [ CI , 0.86 to 1.39 ] ) . Patients in the intervention group tended to have fewer potential ADEs ( unadjusted incidence rate ratio , 0.80 [ CI , 0.61 to 1.04 ] ) . LIMITATION The characteristics of the study hospitals and participants may limit generalizability . CONCLUSION Clinical ly important medication errors were present among one half of patients after hospital discharge and were not significantly reduced by a health-literacy-sensitive , pharmacist-delivered intervention . PRIMARY FUNDING SOURCE National Heart , Lung , and Blood Institute Background : Internal hospital transfer is a vulnerable time during which patients are at high risk of medication discrepancies that can result in clinical ly significant harm , medication errors , and adverse drug events . Objective : To identify , characterize , and assess the clinical impact of unintentional medication discrepancies during internal hospital transfer and to investigate the influence of computerized prescriber order entry ( CPOE ) on medication discrepancies . Methods : All patients transferred between 10 inpatient units at 2 tertiary care hospitals were prospect ively assessed to identify discrepancies . Interfaces included transfers between ( 1 ) units that both used paper-based medication ordering systems ; ( 2 ) units that both used CPOE-based systems ; and ( 3 ) units that used both paper-based and CPOE-based systems ( hybrid transfer ) . The primary endpoint was the number of patients with at least 1 unintentional medication discrepancy during internal hospital transfer . Discrepancies were identified through assessment and comparison of a best possible medication transfer list with the actual transfer orders . A multidisciplinary team of clinicians assessed the potential clinical impact and severity of unintentional discrepancies . Results : Overall , 190 patients were screened and 129 patients were included . Eighty patients ( 62.0 % ) had at least 1 unintentional medication discrepancy at the time of transfer , and the most common discrepancy was medication omission ( 55.6 % ) . Factors that independently increased the risk of a patient experiencing at least 1 unintentional discrepancy included lack of best possible medication history , increasing number of home medications , and increasing number of transfer medications . Forty-seven patients ( 36.4 % ) had at least 1 unintentional discrepancy with the potential to cause discomfort and /or clinical deterioration . The risk of discrepancies was present regardless of the medication-ordering system ( paper , CPOE , or hybrid ) . Conclusions : Clinical ly significant medication discrepancies occur commonly during internal hospital transfer . A structured , collaborative , and clearly defined medication reconciliation process is needed to prevent internal transfer discrepancies and patient harm Background Medication reconciliation has been m and ated by the Irish government at transfer of care . Research is needed to determine the contribution of clinical pharmacists to the process . Objective To describe the contribution of emergency department based clinical pharmacists to admission medication reconciliation in Irel and . Main Outcome Measure Frequency of clinical pharmacist ’s activities . Setting Two public university teaching hospitals . Methodology Adults admitted via the accident and emergency department , from a non-acute setting , reporting the use of at least three regular prescription medications , were eligible for inclusion . Medication reconciliation was provided by clinical pharmacists to r and omly-selected patients within 24-hours of admission . This process includes collecting a gold-st and ard pre-admission medication list , checking this against the admission prescription and communicating any changes . A discrepancy was defined as any difference between the gold-st and ard pre-admission medication list and the admission prescription . Discrepancies were communicated to the clinician in the patient ’s healthcare record . Potentially harmful discrepancies were also communicated verbally . Pharmacist activities and unintentional discrepancies , both resolved and unresolved at 48-hours were measured . Unresolved discrepancies were confirmed verbally by the team as intentional or unintentional . A reliable and vali date d tool was used to assess clinical significance by medical consultants , clinical pharmacists , community pharmacists and general practitioners . Results In total , 134 patients , involving 1,556 medications , were included in the survey . Over 97 % of patients ( involving 59 % of medications ) experienced a medication change on admission . Over 90 % of patients ( involving 29 % of medications ) warranted clinical pharmacy input to determine whether such changes were intentional or unintentional . There were 447 interventions by the clinical pharmacist regarding apparently unintentional discrepancies , a mean of 3.3 per patient . In total , 227 ( 50 % ) interventions were accepted and discrepancies resolved . At 48-hours under half ( 46 % ) of patients remained affected by an unintentional unresolved discrepancy ( 60 % related to omissions ) . Verbally communicated discrepancies were more likely to be resolved than those not communicated verbally ( Chi-square ( 1 ) = 30.029 p < 0.05 ) . Under half of unintentional unresolved discrepancies ( 46 % ) had the potential to cause minor harm compared to 70 % of the resolved unintentional discrepancies . None had the potential to result in severe harm . Conclusion Clinical pharmacists contribute positively to admission medication reconciliation and should be engaged to deliver this service in Irel and Objective : This study aim ed to evaluate the use of a shared electronic primary health care record ( EHR ) to assist with medicines reconciliation in the hospital from admission to discharge . Methods : This is a prospect i ve cross-sectional , comparison evaluation for 2 phases , in a short-term elderly admissions ward in the United Kingdom . In phase 1 , full reconciliation of the medication history was attempted , using conventional methods , before accessing the EHR , and then the EHR was used to verify the reconciliation . In phase 2 , the EHR was the initial method of retrieving the medication history-vali date d by conventional methods . Results : Where reconciliation was led by conventional methods , and before any access to the EHR was attempted , 28 ( 28 % ) of hospital prescriptions were found to contain errors . Of 99 prescriptions subsequently checked using the EHR , only 50 ( 50 % ) matched the EHR . Of the remainder , 25 % of prescriptions contained errors when verified by the EHR . However , 26 % of patients had an incorrect list of current medications on the EHR . Using the EHR as the primary method of reconciliation , 33 ( 32 % ) of 102 prescriptions matched the EHR . Of those that did not match , 39 ( 38 % ) of prescriptions were found to contain errors . Furthermore , 37 ( 36 % ) of patients had an incorrect list of current medications on the EHR . The most common error type on the discharge prescription was drug omission ; and on the EHR , wrong drug . Common potentially serious errors were related to unidentified allergies and adverse drug reactions . Conclusions : The EHR can reduce medication errors . However , the EHR should be seen as one of a range of information sources for reconciliation ; the primary source being the patient or their carer . Both primary care and hospital clinicians should have read- and -write access to the EHR to reduce errors at care transitions . We recommend further evaluation studies 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 OBJECTIVES The objective of this study was to evaluate the quality of medication information available in medical charts before and after the implementation of a medication reconciliation form . PATIENTS AND METHODS This study is a retrospective chart review of patients under 18 years who were taking two medications or more at home and were admitted to a paediatric hospital for more than 24 hours and discharged from a general paediatrics , infectious disease , gastroenterology or pneumology ward over two 20-week periods ( pre- and post-implementation ) . Each week , 10 medical records were r and omly chosen and review ed . The quality of the medication information was measured on admission ( dose , route of administration and frequency ) and on discharge ( dose , route of administration , frequency and duration of treatment ) . The proportion of medications that fully met these criteria was compared between the groups using the chi-squared test . RESULTS Information was analysed for a total of 3275 medications in the pre-implementation group , vs. 3240 medications in the post-implementation group . Baseline characteristics were similar in both groups . On admission , the quality of medication information was comparable between the pre- and post-implementation groups ( 29.1 vs. 29.3 % , respectively ; P = 0.86 ) . However , on discharge , an improvement in the quality of information was observed in the post-implementation group ( 51.7 vs. 65.2 % ; P < 0.001 ) . CONCLUSION Our study demonstrated that the forms used in the reconciliation process , in particular the discharge prescription , could increase the quality of the information related to drug use in medical charts . We believe that medication reconciliation forms should be widely used by all the health care professional teams involved in the drug history or prescription process BACKGROUND Medication reconciliation process has proved to be an effective tool to improve the safety of drug use . The objective of this study was to assess the impact of an intervention aim ed to decrease unintended discrepancies between patient 's usual treatment and medications prescribed on admission to the Department of Internal Medicine . METHODS A quasi-experimental study was carried out from June 2009 to May 2010 , analyzing discrepancies between home medication and drugs prescribed in a tertiary care hospital , before ( first phase ) and after ( second phase ) an electronic reconciliation tool was introduced at admission . This tool connected patients ' usual medication with the electronic prescription program . The research team was made up of two hospital pharmacists , two nurses and three physicians from the Internal and Preventive Medicine Departments . RESULTS During the two phases of the study , 162 patients were included with a total of 1,959 medicines reconciled . The incidence of unintended discrepancies decreased from 3.5 % to 1.8 % after the intervention ( p value 0.03 ) . The proportion of patients with at least one unintended discrepancy was 23.7 % in the first phase and 14.6 % in the second phase ( p value 0.20 ) . Omission was the most common unintended discrepancy . Asthmatic patients showed 6 times higher risk of being affected by an unintended discrepancy ( OR 6.37 , 95%CI 1.6 - 25.5 ; p value 0.009 ) . CONCLUSIONS Implementing a computerized tool integrated into the electronic prescribing program could be very helpful to develop a medication reconciliation process . It is essential to involve all hospital staff in this process BACKGROUND Medication histories acquired upon admission are often incomplete . Using a st and ardized approach warrants more complete medication reconciliation , however , this is too time consuming to be performed . Other strategies guaranteeing complete medication histories should be explored . We developed a limited list of st and ardized questions and assessed its impact on completeness of medication histories . METHODS This prospect i ve study enrolled adults presenting to a tertiary care emergency department . In the control group , medication histories were conducted by physicians of general internal medicine conform st and ard care . In the intervention group , the physicians were obliged to use , besides the st and ard care , the ' limited questions list ' for medication history acquisition . The clinical pharmacist re-obtained medication histories of the patients in both groups using a st and ardized approach . The primary outcome was the impact of the use of a ' limited questions list ' on the frequency of drug omissions in medication histories . RESULTS 260 consecutive patients were enrolled : 130 in the intervention group and 130 in the control group . There was a significant reduction of 49.3 % in drug omissions in the intervention group . The omission rate per medication history was 1.1 for the control group , which was significantly lower ( 0.6 ) in the intervention group . Antithrombotics were most frequently forgotten in the control care group as opposed to dietary supplements in the intervention group . CONCLUSION Drug omission rate in medication histories can be significantly reduced if a limited list of simple questions is used during anamnesis . Widespread use of this tool should be considered to be implemented Seamless care is the desirable continuity of care delivered to a patient in the healthcare system across the spectrum of caregivers and their environments . Medication Reconciliation is one component of seamless pharmaceutical care . A r and omized controlled trial , carried out over nine months with a six-month follow-up period , investigated the impact of a pharmacist-directed seamless care service . Intervention patients admitted to one of two general medicine units were subjected to a comprehensive seamless care discharge process as they were discharged from a regional , academically affiliated hospital in Moncton , NB . The number , type and potential clinical impact of drug-therapy problems for seamless monitoring ( DTPsm ) and drug-therapy inconsistencies and omissions ( DTIOs ) in hospital discharge medications were measured . A total of 253 patients , with 134 patients in the intervention group and 119 in the control group , completed the study . An average of 3.59 DTPsm per intervention patient , with 72.1 % of these being scored as having a significant or very significant clinical impact level , were communicated to community pharmacists . Ninety-nine DTIOs were identified and resolved in intervention patients before discharge . A retrospective medical chart review demonstrated that the intervention resolved almost all DTIOs . In conclusion , a pharmacist-directed seamless care service had a significant impact on drug-related clinical outcomes and processes of care 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 . BACKGROUND Medication reconciliation can prevent some adverse drug events ( ADEs ) . Our prospect i ve study explored whether an easily replicable nurse-pharmacist led medication reconciliation process could efficiently and inexpensively prevent potential ADEs . METHODS Nurses at a 1000 bed urban , tertiary care hospital developed the home medication list ( HML ) through patient interview . If a patient was not able to provide a written HML or recall medications , the nurses review ed the electronic record along with other sources . The nurses then compared the HML to the patient 's active inpatient medications and judged whether the discrepancies were intentional or potentially unintentional . This was repeated at discharge as well . If the prescriber changed the order when contacted about a potential unintentional discrepancy , it was categorized as unintentional and rated on a 1 - 3 potential harm scale . RESULTS The study included 563 patients . HML information gathering averaged 29 minutes . Two hundred twenty-five patients ( 40 % ; 95 % confidence interval [ CI ] , 36%-44 % ) had at least 1 unintended discrepancy on admission or discharge . One hundred sixty-two of the 225 patients had an unintended discrepancy ranked 2 or 3 on the harm scale . It cost $ 113.64 to find 1 potentially harmful discrepancy . Based on the 2008 cost of an ADE , preventing 1 discrepancy in every 290 patient encounters would offset the intervention costs . We potentially averted 81 ADEs for every 290 patients . CONCLUSION Potentially harmful medication discrepancies occurred frequently at both admission and discharge . A nurse-pharmacist collaboration allowed many discrepancies to be reconciled before causing harm . The collaboration was efficient and cost-effective , and the process potentially improves patient safety PURPOSE Medication errors are an important patient safety issue . Electronic medication reconciliation is a system design ed to correct medication discrepancies at transitions in healthcare . The purpose of this paper is to measure types and prevalence of intravenous antibiotic errors at hospital discharge before and after the addition of an electronic discharge medication reconciliation tool ( EDMRT ) . DESIGN / METHODOLOGY /APPROACH A retrospective study was conducted at a tertiary hospital where house officers order discharge medications . In total , 100 pre-EDMRT and 100 post-EDMRT subjects were r and omly recruited from the study center 's clinical Outpatient Parenteral Antimicrobial Therapy ( OPAT ) program . Using infectious disease consultant recommendations as gold st and ard , each antibiotic listed in these consultant notes was compared to the hospital discharge orders to ascertain the primary outcome : presence of an intravenous antibiotic error in the discharge orders . The primary covariate of interest was pre- vs post-EDMRT group . After generating the crude prevalence of antibiotic errors , logistic regression accounted for potential confounding : discharge day ( weekend vs weekday ) , average years of practice by prescribing physician , inpatient service ( medicine vs surgery ) and number of discharge mediations per patient . FINDINGS Prevalence of medication errors decreased from 30 percent ( 30/100 ) among pre-EDMRT subjects to 15 percent ( 15/100 ) errors among post-EDMRT subjects . Dosage errors were the most common type of medication error . The adjusted odds ratio of discharge with intravenous antibiotic error in the post-EDMRT era was 0.39 ( 0.18 , 0.87 ) compared to the pre-EDMRT era . In the adjusted model , the total number of discharge medications was associated with increased OR of discharge error . ORIGINALITY/VALUE To the authors ' knowledge , no other study has examined the impact of reconciliation on types and prevalence of medication errors at hospital discharge . The focus on intravenous antibiotics as a class of high-stakes medications with serious risks to patient safety during error events highlights the clinical importance of the findings . Electronic medication reconciliation may be an important tool in efforts to improve patient safety |
12,956 | 28,105,070 | Capecitabine is an acceptable and more convenient alternative to infusional 5-FU in the CRT for localised SCCAC , offering similar clinical CRR to those reported by phase-III trials | BACKGROUND The st and ard treatment for localised squamous cell carcinoma of the anal canal ( SCCAC ) is chemoradiotherapy ( CRT ) with infusional 5-fluorouracil ( 5-FU ) and mitomycin .
Because 5-FU and capecitabine have offered similar efficacy in many phase-III trials of solid tumours , studies have tested capecitabine in this setting of SCCAC .
However , these studies are small and have reported variable results .
Therefore , a systematic review and meta- analysis was performed . | BACKGROUND To compare capecitabine/cisplatin with 5-fluorouracil/cisplatin as first-line treatment for advanced gastric cancer ( AGC ) . PATIENTS AND METHODS In this r and omised , open-label , phase III study , patients received cisplatin ( 80 mg/m(2 ) i.v . day 1 ) plus oral capecitabine ( 1000 mg/m(2 ) b.i.d . , days 1 - 14 ) ( XP ) or 5-FU ( 800 mg/m(2)/day by continuous infusion , days 1 - 5 ) ( FP ) every 3 weeks . The primary end point was to confirm noninferiority of XP versus FP for progression-free survival ( PFS ) . RESULTS A total of 316 patients were r and omised to XP ( n = 160 ) or FP ( n = 156 ) . In the per- protocol population , median PFS for XP ( n = 139 ) versus FP ( n = 137 ) was 5.6 versus 5.0 months . The primary end point was met with an unadjusted hazard ratio ( HR ) of 0.81 [ 95 % confidence interval ( CI ) 0.63 - 1.04 , P < 0.001 versus noninferiority margin of 1.25 ] . Median overall survival was 10.5 versus 9.3 months for XP versus FP ( unadjusted HR = 0.85 , 95 % CI 0.64 - 1.13 , P = 0.008 versus noninferiority margin of 1.25 ) . The most common treatment-related grade 3/4 adverse events in XP versus FP patients were as follows : neutropenia ( 16 % versus 19 % ) , vomiting ( 7 % versus 8 % ) , and stomatitis ( 2 % versus 6 % ) . CONCLUSIONS XP showed significant noninferiority for PFS versus FP in the first-line treatment of AGC . XP can be considered an effective alternative to FP Summary This was a phase II study of capecitabine in substitution of 5-fluorouracil ( 5-FU ) in the chemoradiotherapy regimen for patients with localized squamous cell carcinoma of the anal canal . Background Combined chemoradiation with infusional 5-FU and mitomycin is the st and ard treatment for localized squamous cell carcinoma ( SCC ) of the anal canal . Capecitabine is an oral fluoropirimidine that has been shown to be equally effective to 5-FU in many solid tumors . However , the efficacy of the substitution of 5-FU for capecitabine in anal SCC needs confirmation . Methods Patients with SCC of anal cancer T2 - 4N0M0 or T ( any ) N1 - 3M0 , with good performance status and normal blood and renal function , were treated with capecitabine 825 mg/m2 bid during radiotherapy associated with a single dose of mitomycin 15 mg/m2 on day 1 . The primary objective was local control rate at 6 months determined by clinical examination and radiological assessment . Sample size was calculated using the Fleming single-stage design . Results From November 2010 to February 2014 , N = 51 patients were initially included ; however , 43 patients were assessed . Seventeen patients ( 39.5 % ) were stage II , 11 patients ( 25.6 % ) stage IIIA , and 15 patients ( 34.9 % ) stage IIIB . Four patients ( 9.3 % ) were HIV positive . With a median follow-up of 23.1 months ( range 4 to 44.4 months ) , 3 patients ( 7 % ) presented partial response , 37 ( 86 % ) had complete response , and 3 patients developed progression of the disease ( 7 % ) at 6 months . The colostomy rate was 18.6 % . It was observed a locoregional control of 86 % in 6 months ( CI 95 % 0.72–0.94 ) . The main grade 3–4 toxicities were grade 3 radiodermitis in 10 patients ( 23.2 % ) , grade 3 lymphopenia in 5 patients ( 11.6 % ) , and grade 3 neutropenia in 2 patients ( 6.9 % ) . One HIV-positive patient had septic shock , pneumonia , herpetic encephalitis , atrial fibrillation , and macrophage activation syndrome . Conclusions Capecitabine can safely substitute infusional 5-FU in the st and ard chemoradiation regimen for SCC of the anal cancer , with a locoregional control of 86 % in 6 months ( CI 95 % 0.72–0.94 ) PURPOSE On initial publication of GI Intergroup Radiation Therapy Oncology Group ( RTOG ) 98 - 11 [ A Phase III R and omized Study of 5-Fluorouracil ( 5-FU ) , Mitomycin , and Radiotherapy Versus 5-Fluorouracil , Cisplatin and Radiotherapy in Carcinoma of the Anal Canal ] , concurrent chemoradiation ( CCR ) with fluorouracil ( FU ) plus mitomycin ( MMC ) decreased colostomy failure ( CF ) when compared with induction plus concurrent FU plus cisplatin ( CDDP ) , but did not significantly impact disease-free survival ( DFS ) or overall survival ( OS ) for anal canal carcinoma . The intent of the up date d analysis was to determine the long-term impact of treatment on survival ( DFS , OS , colostomy-free survival [ CFS ] ) , CF , and relapse ( locoregional failure [ LRF ] , distant metastasis ) in this patient group . PATIENTS AND METHODS Stratification factors included sex , clinical node status , and primary size . DFS and OS were estimated univariately by the Kaplan-Meier method , and treatment arms were compared by log-rank test . Time to relapse and CF were estimated by the cumulative incidence method and treatment arms were compared by using Gray 's test . Multivariate analyses used Cox proportional hazard models to test for treatment differences after adjusting for stratification factors . RESULTS Of 682 patients accrued , 649 were analyzable for outcomes . DFS and OS were statistically better for RT + FU/MMC versus RT + FU/CDDP ( 5-year DFS , 67.8 % v 57.8 % ; P = .006 ; 5-year OS , 78.3 % v 70.7 % ; P = .026 ) . There was a trend toward statistical significance for CFS ( P = .05 ) , LRF ( P = .087 ) , and CF ( P = .074 ) . Multivariate analysis was statistically significant for treatment and clinical node status for both DFS and OS , for tumor diameter for DFS , and for sex for OS . CONCLUSION CCR with FU/MMC has a statistically significant , clinical ly meaningful impact on DFS and OS versus induction plus concurrent FU/CDDP , and it has borderline significance for CFS , CF , and LRF . Therefore , RT + FU/MMC remains the preferred st and ard of care PURPOSE To investigate the potential gain of the concomitant use of radiotherapy and chemotherapy in improving local control and reducing the need for colostomy , a r and omized phase III trial was performed in patients with locally advanced anal cancer . MATERIAL S AND METHODS From 1987 to 1994 , 110 patients were r and omized between radiotherapy alone and a combination of radiotherapy and chemotherapy . The patients had T3 - 4NO-3 or T1 - 2N1 - 3 anal cancer . Radiotherapy consisted of 45 Gy given in 5 weeks , with a daily dose of 1.8 Gy . After a rest period of 6 weeks , a boost of 20 or 15 Gy was given in case of partial or complete response , respectively . Surgical resection as part of the primary treatment was performed if possible in patients who had not responded 6 weeks after 45 Gy or with residual palpable disease after the completion of treatment . Chemotherapy was given during radiotherapy : 750 mg/m2 daily fluorouracil as a continuous infusion on days 1 to 5 and 29 to 33 , and a single dose of mitomycin 15 mg/m2 administered on day 1 . RESULTS The addition of chemotherapy to radiotherapy result ed in a significant increase in the complete remission rate from 54 % for radiotherapy alone to 80 % for radiotherapy and chemotherapy , and from 85 % to 96 % , respectively , if results are considered after surgical resections . This led to a significant improvement of locoregional control and colostomy-free interval ( P = .02 and P = .002 , respectively ) , both in favor of the combined modality treatment . The locoregional control rate improved by 18 % at 5 years , while the colostomy-free rate at that time increased by 32 % by the addition of chemotherapy to radiotherapy . No significant difference was found when severe side effects were considered , although anal ulcers were more frequently observed in the combined-treatment arm . The survival rate remained similar in both treatment arms . Skin ulceration , nodal involvement , and sex were the most important prognostic factors for both local control and survival . These remained significant after multivariate analysis . The improvement seen in local control by adding chemotherapy to radiotherapy also remained significant after adjusting for prognostic factors in the multivariate analysis . Event-free survival , defined as free of locoregional progression , no colostomy , and no severe side effects or death , showed significant improvement ( P = .03 ) in favor of the combined-treatment modality . The 5-year survival rate was 56 % for the whole patient group . CONCLUSION The concomitant use of radiotherapy and chemotherapy result ed in a significantly improved locoregional control rate and a reduction of the need for colostomy in patients with locally advanced anal cancer without a significant increase in late side effects CONTEXT Chemoradiation as definitive therapy is the preferred primary therapy for patients with anal canal carcinoma ; however , the 5-year disease-free survival rate from concurrent fluorouracil/mitomycin and radiation is only approximately 65 % . OBJECTIVE To compare the efficacy of cisplatin-based ( experimental ) therapy vs mitomycin-based ( st and ard ) therapy in treatment of anal canal carcinoma . DESIGN , SETTING , AND PARTICIPANTS US Gastrointestinal Intergroup trial RTOG 98 - 11 , a multicenter , phase 3 , r and omized controlled trial comparing treatment with fluorouracil plus mitomycin and radiotherapy vs treatment with fluorouracil plus cisplatin and radiotherapy in 682 patients with anal canal carcinoma enrolled between October 31 , 1998 , and June 27 , 2005 . Stratifications included sex , clinical nodal status , and tumor diameter . INTERVENTION Participants were r and omly assigned to 1 of 2 intervention groups : ( 1 ) the mitomycin-based group ( n = 341 ) , who received fluorouracil ( 1000 mg/m2 on days 1 - 4 and 29 - 32 ) plus mitomycin ( 10 mg/m2 on days 1 and 29 ) and radiotherapy ( 45 - 59 Gy ) or ( 2 ) the cisplatin-based group ( n = 341 ) , who received fluorouracil ( 1000 mg/m2 on days 1 - 4 , 29 - 32 , 57 - 60 , and 85 - 88 ) plus cisplatin ( 75 mg/m2 on days 1 , 29 , 57 , and 85 ) and radiotherapy ( 45 - 59 Gy ; start day = day 57 ) . MAIN OUTCOME MEASURES The primary end point was 5-year disease-free survival ; secondary end points were overall survival and time to relapse . RESULTS A total of 644 patients were assessable . The median follow-up for all patients was 2.51 years . Median age was 55 years , 69 % were women , 27 % had a tumor diameter greater than 5 cm , and 26 % had clinical ly positive nodes . The 5-year disease-free survival rate was 60 % ( 95 % confidence interval [ CI ] , 53%-67 % ) in the mitomycin-based group and 54 % ( 95 % CI , 46%-60 % ) in the cisplatin-based group ( P = .17 ) . The 5-year overall survival rate was 75 % ( 95 % CI , 67%-81 % ) in the mitomycin-based group and 70 % ( 95 % CI , 63%-76 % ) in the cisplatin-based group ( P = .10 ) . The 5-year local-regional recurrence and distant metastasis rates were 25 % ( 95 % CI , 20%-30 % ) and 15 % ( 95 % CI , 10%-20 % ) , respectively , for mitomycin-based treatment and 33 % ( 95 % CI , 27%-40 % ) and 19 % ( 95 % CI , 14%-24 % ) , respectively , for cisplatin-based treatment . The cumulative rate of colostomy was significantly better for mitomycin-based than cisplatin-based treatment ( 10 % vs 19 % ; P = .02 ) . Severe hematologic toxicity was worse with mitomycin-based treatment ( P < .001 ) . CONCLUSIONS In this population of patients with anal canal carcinoma , cisplatin-based therapy failed to improve disease-free-survival compared with mitomycin-based therapy , but cisplatin-based therapy result ed in a significantly worse colostomy rate . These findings do not support the use of cisplatin in place of mitomycin in combination with fluorouracil and radiotherapy in the treatment of anal canal carcinoma . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00003596 PURPOSE Definitive chemoradiation ( CR ) has replaced radical surgery as the preferred treatment of epidermoid carcinoma of the anal canal . To determine the importance of mitomycin ( MMC ) in the st and ard CR regimen and to assess the role of salvage CR in patients who have residual tumor following CR , a phase III r and omized trial was undertaken by the Radiation Therapy Oncology Group (RTOG)/Eastern Cooperative Oncology Group ( ECOG ) . PATIENTS AND METHODS Between August 1988 and December 1991 , 310 patients were r and omized to receive either radiotherapy ( RT ) and fluorouracil ( 5-FU ) or radiotherapy , 5-FU , and MMC . Of 291 assessable patients , 145 received 45 to 50.4 Gy of pelvic RT plus 5-FU at 1,000 mg/m2/d for 4 days , and 146 received RT , 5-FU , and MMC ( 10 mg/m2 per dose for two doses ) . Patients with residual tumor on posttreatment biopsy were treated with a salvage regimen that consisted of additional pelvic RT ( 9 Gy ) , 5-FU , and cisplatin ( 100 mg/m2 ) . RESULTS Posttreatment biopsies were positive in 15 % of patients in the 5-FU arm versus 7.7 % in the MMC arm ( P = .135 ) . At 4 years , colostomy rates were lower ( 9 % v 22 % ; P = .002 ) , colostomy-free survival higher ( 71 % v 59 % ; P = .014 ) , and disease-free survival higher ( 73 % v 51 % ; P = .0003 ) in the MMC arm . A significant difference in overall survival has not been observed at 4 years . Toxicity was greater in the MMC arm ( 23 % v 7 % grade 4 and 5 toxicity ; P < or = .001 ) . Of 24 assessable patients who underwent salvage CR , 12 ( 50 % ) were rendered disease-free . CONCLUSION Despite greater toxicity , the use of MMC in a definitive CR regimen for anal cancer is justified , particularly in patients with large primary tumors . Salvage CR should be attempted in patients with residual disease following definitive CR before resorting to radical surgery BACKGROUND We evaluated capecitabine ( an oral fluoropyrimidine ) and oxaliplatin ( a platinum compound ) as alternatives to infused fluorouracil and cisplatin , respectively , for untreated advanced esophagogastric cancer . METHODS In a two-by-two design , we r and omly assigned 1002 patients to receive triplet therapy with epirubicin and cisplatin plus either fluorouracil ( ECF ) or capecitabine ( ECX ) or triplet therapy with epirubicin and oxaliplatin plus either fluorouracil ( EOF ) or capecitabine ( EOX ) . The primary end point was noninferiority in overall survival for the triplet therapies containing capecitabine as compared with fluorouracil and for those containing oxaliplatin as compared with cisplatin . RESULTS For the capecitabine-fluorouracil comparison , the hazard ratio for death in the capecitabine group was 0.86 ( 95 % confidence interval [ CI ] , 0.80 to 0.99 ) ; for the oxaliplatin-cisplatin comparison , the hazard ratio for the oxaliplatin group was 0.92 ( 95 % CI , 0.80 to 1.10 ) . The upper limit of the confidence intervals for both hazard ratios excluded the predefined noninferiority margin of 1.23 . Median survival times in the ECF , ECX , EOF , and EOX groups were 9.9 months , 9.9 months , 9.3 months , and 11.2 months , respectively ; survival rates at 1 year were 37.7 % , 40.8 % , 40.4 % , and 46.8 % , respectively . In the secondary analysis , overall survival was longer with EOX than with ECF , with a hazard ratio for death of 0.80 in the EOX group ( 95 % CI , 0.66 to 0.97 ; P=0.02 ) . Progression-free survival and response rates did not differ significantly among the regimens . Toxic effects of capecitabine and fluorouracil were similar . As compared with cisplatin , oxaliplatin was associated with lower incidences of grade 3 or 4 neutropenia , alopecia , renal toxicity , and thromboembolism but with slightly higher incidences of grade 3 or 4 diarrhea and neuropathy . CONCLUSIONS Capecitabine and oxaliplatin are as effective as fluorouracil and cisplatin , respectively , in patients with previously untreated esophagogastric cancer . ( Current Controlled Trials number , IS RCT N51678883 [ controlled-trials.com ] . ) PURPOSE A multi-institutional phase 2 trial assessed the utility of dose-painted intensity modulated radiation therapy ( DP-IMRT ) in reducing grade 2 + combined acute gastrointestinal and genitourinary adverse events ( AEs ) of 5-fluorouracil ( 5FU ) and mitomycin-C ( MMC ) chemoradiation for anal cancer by at least 15 % compared with the conventional radiation/5FU/MMC arm from RTOG 9811 . METHODS AND MATERIAL S T2 - 4N0 - 3M0 anal cancer patients received 5FU and MMC on days 1 and 29 of DP-IMRT , prescribed per stage : T2N0 , 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes ( PTVs ) in 28 fractions ; T3 - 4N0 - 3 , 45 Gy elective nodal , 50.4 Gy ≤ 3 cm or 54 Gy > 3 cm metastatic nodal and 54 Gy anal tumor PTVs in 30 fractions . The primary endpoint is described above . Planned secondary endpoints assessed all AEs and the investigator 's ability to perform DP-IMRT . RESULTS Of 63 accrued patients , 52 were evaluable . Tumor stage included 54 % II , 25 % IIIA , and 21 % IIIB . In primary endpoint analysis , 77 % experienced grade 2 + gastrointestinal/genitourinary acute AEs ( 9811 77 % ) . There was , however , a significant reduction in acute grade 2 + hematologic , 73 % ( 9811 85 % , P=.032 ) , grade 3 + gastrointestinal , 21 % ( 9811 36 % , P=.0082 ) , and grade 3 + dermatologic AEs 23 % ( 9811 49 % , P<.0001 ) with DP-IMRT . On initial pretreatment review , 81 % required DP-IMRT replanning , and final review revealed only 3 cases with normal tissue major deviations . CONCLUSIONS Although the primary endpoint was not met , DP-IMRT was associated with significant sparing of acute grade 2 + hematologic and grade 3 + dermatologic and gastrointestinal toxicity . Although DP-IMRT proved feasible , the high pretreatment planning revision rate emphasizes the importance of real-time radiation quality assurance for IMRT trials BACKGROUND Non-surgical management of anal cancer by radiotherapy alone or combined with chemotherapy has , in uncontrolled studies , yielded similar local tumour control and survival rates to surgery . However , whether the addition of chemotherapy improves outcome without adding to morbidity is not known . Our trial was design ed to compare combined modality therapy ( CMT ) with radiotherapy alone in patients with epidermoid anal cancer . METHODS From 856 patients considered for entry to our multicentre trial , 585 patients were r and omised to receive initially either 45 Gy radiotherapy in twenty or twenty-five fractions over 4 - 5 weeks ( 290 patients ) or the same regimen of radiotherapy combined with 5-fluorouracil ( 1000 mg/m2 for 4 days or 750 mg/m2 for 5 days ) by continuous infusion during the first and the final weeks of radiotherapy and mitomycin ( 12 mg/m2 ) on day 1 of the first course ( 295 patients ) . We assessed clinical response 6 weeks after initial treatment : good responders were recommended for boost radiotherapy and poor responders for salvage surgery . The main endpoint was local-failure rate ( > or = 6 weeks after initial treatment ) ; secondary endpoints were overall and cause-specific survival . Analysis was by intention-to-treat . FINDINGS In the radiotherapy and CMT arms , respectively , five and three were ineligible , and six and nine died 6 weeks after initial treatment . After a median follow-up of 42 months ( interquartile range 28 - 62 ) , 164 of 279 ( 59 % ) radiotherapy patients had a local failure compared with 101 of 283 ( 36 % ) CMT patients . This gave a 46 % reduction in the risk of local failure in the patients receiving CMT ( relative risk 0.54 , 95 % CI 0.42 - 0.69 , p < 0.0001 ) . The risk of death from anal cancer was also reduced in the CMT arm ( 0.71 , 0.53 - 0.95 , p = 0.02 ) . There was no overall survival advantage ( 0.86 , 0.67 - 1.11 , p = 0.25 ) . Early morbidity was significantly more frequent in the CMT arm ( p = 0.03 ) , but late morbidity occurred at similar rates . INTERPRETATION Our trial shows that the st and ard treatment for most patients with epidermoid anal cancer should be a combination of radiotherapy and infused 5-fluorouracil and mitomycin , with surgery reserved for those who fall on this regimen BACKGROUND Intravenous bolus fluorouracil plus leucovorin is the st and ard adjuvant treatment for colon cancer . The oral fluoropyrimidine capecitabine is an established alternative to bolus fluorouracil plus leucovorin as first-line treatment for metastatic colorectal cancer . We evaluated capecitabine in the adjuvant setting . METHODS We r and omly assigned a total of 1987 patients with resected stage III colon cancer to receive either oral capecitabine ( 1004 patients ) or bolus fluorouracil plus leucovorin ( Mayo Clinic regimen ; 983 patients ) over a period of 24 weeks . The primary efficacy end point was at least equivalence in disease-free survival ; the primary safety end point was the incidence of grade 3 or 4 toxic effects due to fluoropyrimidines . RESULTS Disease-free survival in the capecitabine group was at least equivalent to that in the fluorouracil-plus-leucovorin group ( in the intention-to-treat analysis , P<0.001 for the comparison of the upper limit of the hazard ratio with the noninferiority margin of 1.20 ) . Capecitabine improved relapse-free survival ( hazard ratio , 0.86 ; 95 percent confidence interval , 0.74 to 0.99 ; P=0.04 ) and was associated with significantly fewer adverse events than fluorouracil plus leucovorin ( P<0.001 ) . CONCLUSIONS Oral capecitabine is an effective alternative to intravenous fluorouracil plus leucovorin in the adjuvant treatment of colon cancer BACKGROUND Fluorouracil-based chemoradiotherapy is regarded as a st and ard perioperative treatment in locally advanced rectal cancer . We investigated the efficacy and safety of substituting fluorouracil with the oral prodrug capecitabine . METHODS This r and omised , open-label , multicentre , non-inferiority , phase 3 trial began in March , 2002 , as an adjuvant trial comparing capecitabine-based chemoradiotherapy with fluorouracil-based chemoradiotherapy , in patients aged 18 years or older with pathological stage II-III locally advanced rectal cancer from 35 German institutions . Patients in the capecitabine group were scheduled to receive two cycles of capecitabine ( 2500 mg/m(2 ) days 1 - 14 , repeated day 22 ) , followed by chemoradiotherapy ( 50·4 Gy plus capecitabine 1650 mg/m(2 ) days 1 - 38 ) , then three cycles of capecitabine . Patients in the fluorouracil group received two cycles of bolus fluorouracil ( 500 mg/m(2 ) days 1 - 5 , repeated day 29 ) , followed by chemoradiotherapy ( 50·4 Gy plus infusional fluorouracil 225 mg/m(2 ) daily ) , then two cycles of bolus fluorouracil . The protocol was amended in March , 2005 , to allow a neoadjuvant cohort in which patients in the capecitabine group received chemoradiotherapy ( 50·4 Gy plus capecitabine 1650 mg/m(2 ) daily ) followed by radical surgery and five cycles of capecitabine ( 2500 mg/m(2 ) per day for 14 days ) and patients in the fluorouracil group received chemoradiotherapy ( 50·4 Gy plus infusional fluorouracil 1000 mg/m(2 ) days 1 - 5 and 29 - 33 ) followed by radical surgery and four cycles of bolus fluorouracil ( 500 mg/m(2 ) for 5 days ) . Patients were r and omly assigned to treatment group in a 1:1 ratio using permuted blocks , with stratification by centre and tumour stage . The primary endpoint was overall survival ; analyses were done based on all patients with post-r and omisation data . Non-inferiority of capecitabine in terms of 5-year overall survival was tested with a 12·5 % margin . This trial is registered with Clinical Trials.gov , number NCT01500993 . FINDINGS Between March , 2002 , and December , 2007 , 401 patients were r and omly allocated ; 392 patients were evaluable ( 197 in the capecitabine group , 195 in the fluorouracil group ) , with a median follow-up of 52 months ( IQR 41 - 72 ) . 5-year overall survival in the capecitabine group was non-inferior to that in the fluorouracil group ( 76 % [ 95 % CI 67 - 82 ] vs 67 % [ 58 - 74 ] ; p=0·0004 ; post-hoc test for superiority p=0·05 ) . 3-year disease-free survival was 75 % ( 95 % CI 68 - 81 ) in the capecitabine group and 67 % ( 59 - 73 ) in the fluorouracil group ( p=0·07 ) . Similar numbers of patients had local recurrences in each group ( 12 [ 6 % ] in the capecitabine group vs 14 [ 7 % ] in the fluorouracil group , p=0·67 ) , but fewer patients developed distant metastases in the capecitabine group ( 37 [ 19 % ] vs 54 [ 28 % ] ; p=0·04 ) . Diarrhoea was the most common adverse event in both groups ( any grade : 104 [ 53 % ] patients in the capecitabine group vs 85 [ 44 % ] in the fluorouracil group ; grade 3 - 4 : 17 [ 9 % ] vs four [ 2 % ] ) . Patients in the capecitabine group had more h and -foot skin reactions ( 62 [ 31 % ] any grade , four [ 2 % ] grade 3 - 4 vs three [ 2 % ] any grade , no grade 3 - 4 ) , fatigue ( 55 [ 28 % ] any grade , no grade 3 - 4 vs 29 [ 15 % ] , two [ 1 % ] grade 3 - 4 ) , and proctitis ( 31 [ 16 % ] any grade , one [ < 1 % ] grade 3 - 4 vs ten [ 5 % ] , one [ < 1 % ] grade 3 - 4 ) than did those in the fluorouracil group , whereas leucopenia was more frequent with fluorouracil than with capecitabine ( 68 [ 35 % ] any grade , 16 [ 8 % ] grade 3 - 4 vs 50 [ 25 % ] any grade , three [ 2 % ] grade 3 - 4 ) . INTERPRETATION Capecitabine could replace fluorouracil in adjuvant or neoadjuvant chemoradiotherapy regimens for patients with locally advanced rectal cancer . FUNDING Roche Pharma AG ( Grenzach-Wyhlen , Germany ) PURPOSE 5-Fluorouracil ( 5-FU ) + mitomycin C (MMC)-based chemoradiotherapy is st and ard treatment for patients with epidermoid anal carcinoma . Clinical trials in other cancers have confirmed 5-FU can successfully be replaced by the oral fluoropyrimidine capecitabine . This phase II trial aim ed to determine the feasibility , toxicity , and efficacy of capecitabine , MMC and radiotherapy ( RT ) in anal cancer patients . METHODS AND MATERIAL S Radiotherapy comprised the schedule of the UK Anal Cancer Trial ( ACT ) II trial ( 50.4 Gy in 28 fractions of 1.8 Gy ) . With MMC ( 12 mg/m2 ) on Day 1 and capecitabine on each RT treatment day in two divided doses ( 825 mg/m2 b.i.d ) . The endpoints were complete response at 4 weeks , local control at 6 months and toxicity . RESULTS Thirty-one patients entered the trial . The median age was 61 years ( range 45 - 86 ) with 14 males and 17 females . Compliance with chemotherapy with no dose interruptions or delays was 68 % , and with RT was 81 % . Eighteen ( 58 % ) patients completed both modalities of treatment as planned . Dose-limiting Grade 3 or 4 diarrhea was seen in 1 of 31 patients . Three patients experienced Grade 3 neutropenia . There were no treatment-related deaths . Four weeks following completion of chemoradiation , 24 patients ( 77 % ) had a complete clinical response , and 4 ( 16 % ) a partial response . With a median follow-up of 14 months , three locoregional relapses occurred . CONCLUSIONS Capecitabine with MMC and RT in with patients anal carcinoma is well tolerated , with minimal toxicity and acceptable compliance . We recommend testing this schedule in future national Phase III studies in anal cancer BACKGROUND Chemoradiation became the st and ard of care for anal cancer after the ACT I trial . However , only two-thirds of patients achieved local control , with 5-year survival of 50 % ; therefore , better treatments are needed . We investigated whether replacing mitomycin with cisplatin in chemoradiation improves response , and whether maintenance chemotherapy after chemoradiation improves survival . METHODS In this 2 × 2 factorial trial , we enrolled patients with histologically confirmed squamous-cell carcinoma of the anus without metastatic disease from 59 centres in the UK . Patients were r and omly assigned to one of four groups , to receive either mitomycin ( 12 mg/m(2 ) on day 1 ) or cisplatin ( 60 mg/m(2 ) on days 1 and 29 ) , with fluorouracil ( 1000 mg/m(2 ) per day on days 1 - 4 and 29 - 32 ) and radiotherapy ( 50.4 Gy in 28 daily fractions ) ; with or without two courses of maintenance chemotherapy ( fluorouracil and cisplatin at weeks 11 and 14 ) . The r and om allocation was generated by computer and patients assigned by telephone . R and omisation was done by minimisation and stratified by tumour site , T and N stage , sex , age , and renal function . Neither patients nor investigators were masked to assignment . Primary endpoints were complete response at 26 weeks and acute toxic effects ( for chemoradiation ) , and progression-free survival ( for maintenance ) . The primary analyses were done by intention to treat . This study is registered at controlled-trials.com , number 26715889 . FINDINGS We enrolled 940 patients : 472 were assigned to mitomycin , of whom 246 were assigned to no maintenance , 226 to maintenance ; 468 were assigned to cisplatin , of whom 246 were assigned to no maintenance , 222 to maintenance . Median follow-up was 5.1 years ( IQR 3.9 - 6.9 ) . 391 of 432 ( 90.5 % ) patients in the mitomycin group versus 386 of 431 ( 89.6 % ) in the cisplatin group had a complete response at 26 weeks ( difference -0.9 % , 95 % CI -4.9 to 3.1 ; p=0.64 ) . Overall , toxic effects were similar in each group ( 334/472 [ 71 % ] for mitomycin vs 337/468 [ 72 % ] for cisplatin ) . The most common grade 3 - 4 toxic effects were skin ( 228/472 [ 48 % ] vs 222/468 [ 47 % ] ) , pain ( 122/472 [ 26 % ] vs 135/468 [ 29 % ] ) , haematological ( 124/472 [ 26 % ] vs 73/468 [ 16 % ] ) , and gastrointestinal ( 75/472 [ 16 % ] vs 85/468 [ 18 % ] ) . 3-year progression-free survival was 74 % ( 95 % CI 69 - 77 ; maintenance ) versus 73 % ( 95 % CI 68 - 77 ; no maintenance ; hazard ratio 0.95 , 95 % CI 0.75 - 1.21 ; p=0.70 ) . INTERPRETATION The results of our trial -- the largest in anal cancer to date --show that fluorouracil and mitomycin with 50.4 Gy radiotherapy in 28 daily fractions should remain st and ard practice in the UK . FUNDING Cancer Research UK PURPOSE Newer radiation techniques , and the application of continuous 5-FU exposure during radiation therapy using oral capecitabine may improve the treatment of anal cancer . This phase 1 , dose-finding study assessed the feasibility and efficacy of simultaneous integrated boost-intensity modulated radiation therapy ( SIB-IMRT ) with concomitant capecitabine and mitomycin C in locally advanced anal cancer , including pharmacokinetic and pharmacogenetic analyses . METHODS AND MATERIAL S Patients with locally advanced anal carcinoma were treated with SIB-IMRT in 33 daily fractions of 1.8 Gy to the primary tumor and macroscopically involved lymph nodes and 33 fractions of 1.5 Gy electively to the bilateral iliac and inguinal lymph node areas . Patients received a sequential radiation boost dose of 3 × 1.8 Gy on macroscopic residual tumor if this was still present in week 5 of treatment . Mitomycin C 10 mg/m(2 ) ( maximum 15 mg ) was administered intravenously on day 1 , and capecitabine was given orally in a dose-escalated fashion ( 500 - 825 mg/m(2 ) b.i.d . ) on irradiation days , until dose-limiting toxicity emerged in ≥2 of maximally 6 patients . An additional 8 patients were treated at the maximum tolerated dose ( MTD ) . RESULTS A total of 18 patients were included . The MTD of capecitabine was determined to be 825 mg/m(2 ) b.i.d . The predominant acute grade ≥3 toxicities included radiation dermatitis ( 50 % ) , fatigue ( 22 % ) , and pain ( 6 % ) . Fifteen patients ( 83 % [ 95%-CI : 66%-101 % ] ) achieved a complete response , and 3 ( 17 % ) patients a partial response . With a median follow-up of 28 months , none of the complete responders , and 2 partial responders had relapsed . CONCLUSIONS SIB-IMRT with concomitant single dose mitomycin C and capecitabine 825 mg/m(2 ) b.i.d . on irradiation days result ed in an acceptable safety profile , and proved to be a tolerable and effective treatment regimen for locally advanced anal cancer |
12,957 | 10,164,145 | MAIN OUTCOME MEASURES : Primary interventions were classified according to whether or not they were supported by evidence from r and omised controlled trials or systematic review s. RESULTS : The primary interventions received by 26/40 ( 65 % ; 95 % confidence interval ( 95 % CI ) 51 % to 79 % ) of patients admitted during the period were based on r and omised trials or systematic review s. CONCLUSIONS : When patients were used as the denominator , most primary interventions given in acute general psychiatry were based on experimental evidence . | OBJECTIVES : To estimate the proportion of psychiatric in patients receiving primary interventions based on r and omised controlled trials or systematic review s of r and omised controlled trials . | A double-blind study of 537 patients evaluated the relative efficacy of four drugs — chlordiazepoxide , chlorpromazine , hydroxyzine , and thiamine — commonly used in treating alcohol withdrawal symptoms , specifically to prevent delirium tremens and convulsions . Of the 55 patients who developed these symptoms , two percent were in the chlordiazepoxide group ; the incidence ranged from ten to 16 percent in the other treatment groups . The authors conclude that chlordiazepoxide appears to be the drug of choice among those tested Zuclopenthixol acetate — a new injectable formulation with a duration of action of 2–3 days — was compared with conventional intramuscular and oral formulations of haloperidol and zuclopenthixol in the initial treatment of acutely disturbed , psychotic patients . The patients were stratified into 3 diagnostic categories : acute psychoses ( 48 patients ) , mania ( 22 patients ) , and exacerbation of chronic psychoses ( 73 patients ) . The patients were rated on the Brief Psychiatric Rating Scale ( BPRS ) , the Bech‐Rafaelsen Mania Rating Scale ( brmas ) ( only manic patients ) and globally on the Clinical Global Impression ( CGI ) . The study was an open , r and omized multicentre trial with a 6‐day treatment period . The zuclopenthixol acetate patients received 1–4 doses , the haloperidol patients 1–26 and the zuclopenthixol patients 1–22 doses . The assessment s on the CGI showed that all 3 treatments caused a clear reduction of the severity of illness scores in all 3 diagnostic categories , with no differences between treatments . The ratings of the acute and chronic psychotic patients on the BPRS also showed significant reductions in scores with no differences between treatments . All 3 treatments caused a rapid remission of symptoms on the BRMAS . Haloperidol induced hypokinesia in significantly more patients than zuclopenthixol acetate after 24 h. Later there were no significant differences between treatments . Zuclopenthixol acetate fulfils many desires for an amended neuroleptic formulation for the initial treatment of acutely disturbed psychotic patients In an 18 hospital study , 205 patients hospitalized with a diagnosis of manic-depressive illness , manic type , were treated upon discharge with lithium carbonate or placebo for a two-year period . Lithium carbonate was significantly more effective than placebo in preventing relapses ( ie , affective episodes severe enough to require hospitalization or use of non study drugs ) . The difference in treatment outcome between lithium carbonate and placebo was due mainly to the lower incidence of manic relapses on lithium carbonate . Patients on lithium carbonate also had a lower incidence of depressive relapses than patients on placebo but the limited incidence of severe depression in this sample makes it difficult to draw any conclusions regarding the prophylactic efficacy of lithium carbonate in depressive illness . The results from this trial coupled with those from other studies indicate that lithium carbonate combined with regular clinical appraisal s is a safe and effective treatment for preventing relapse in manic-depressive illness The merits or otherwise of publishing hospital specific death rates are much debated . This article compares the relative sensitivity of measures of process and outcome to differences in quality of care for the hospital treatment of myocardial infa rct ion . Aspects of hospital care that have a proved impact on mortality from myocardial infa rct ion are identified , and the results from meta- analysis and large r and omised controlled trials are used to estimate the impact that optimal use of these interventions would have on mortality in a typical district general hospital . Sample size calculations are then performed to determine how many years of data would be needed to detect significant differences between hospitals . A comparison is then made with the amount of data that would be needed to detect significant differences if information about process of care was being collected . Process measures based on the results of r and omised controlled trials were found to be able to detect relevant differences between hospitals that would not be identified by comparing hospital specific mortality , which is an insensitive indicator of the quality of care Abstract Objectives : To estimate the proportion of interventions in general practice that are based on evidence from clinical trials and to assess the appropriateness of such an evaluation . Design : Retrospective review of case notes . Setting : One suburban training general practice . Subjects : 122 consecutive doctor-patient consultations over two days . Main outcome measures : Proportions of interventions based on r and omised controlled trials ( from literature search with Medline , pharmaceutical data bases , and st and ard textbooks ) , on convincing non-experimental evidence , and without substantial evidence . Results : 21 of the 122 consultations recorded were excluded due to insufficient data ; 31 of the interventions were based on r and omised controlled trial evidence and 51 based on convincing non-experimental evidence . Hence 82/101 ( 81 % ) of interventions were based on evidence meeting our criteria . Conclusions : Most interventions within general practice are based on evidence from clinical trials , but the methods used in such trials may not be the most appropriate to apply to this setting . Key messages Key messages 81 % of general practice can be described as evidence based using this method of assessment Evidence derived from different method ologies may be important for the assessment of the evidence base of general The phenylpiperidine derivative paroxetine is a selective serotonin reuptake inhibitor . In a double-blind 6-week trial , paroxetine was compared with amitriptyline in hospitalized patients suffering from major depression ( DSM-III ) . One hundred fifty-three patients were enrolled in the study in seven centers in Austria and Germany . Results showed similar efficacy of both drugs after 6 weeks . The differences between groups in Mont-gomery-Asberg Depression Rating Scale and Clinical Global Impression ratings did not reach statistical significance at any time . Side effects were distributed similarly but with a significantly higher incidence of anticholinergic effects in patients treated with amitriptyline ( p < 0.001 ) , whereas agitation and insomnia were registered more often in the paroxetine group . This study supports the antidepressive efficacy of paroxetine in a sample of severely depressed in patients BACKGROUND This study was design ed to establish whether ( as suggested in a number of open and relatively small controlled trials ) lithium augmentation is more effective than continued antidepressant alone , where response to a st and ard course of antidepressant treatment has been absent or partial . METHOD Lithium or placebo was added on a double-blind basis for six weeks to the drug regime of 62 patients with major depressive illness ( in both hospital and primary care setting s ) who had failed to respond to a controlled trial of fluoxetine or lofepramine . Response was defined as a final Hamilton Depression Rating Scale ( HDRS ) score of < 10 . RESULTS Response was seen more frequently in patients taking lithium ( 15/29 ) than in those remaining on antidepressant alone ( 8/32 ; P or = 0.4 mmol/l ) . No differences in the efficacy of LA were apparent between fluoxetine and lofepramine . CONCLUSIONS Our results confirm that LA is a useful strategy in the treatment of antidepressant-resistant depression . Partial response was , however , frequently observed with continued antidepressant treatment alone , and the superiority of LA appears to depend on achieving adequate serum lithium levels For many years clinicians have had to cope with the accusation that only 10 - 20 % of the treatments they provide have any scientific foundation . Their interventions , in other words , are seldom " evidence based " . Is the profession guilty as charged ? In April , 1995 , a general medical team at a university-affiliated district hospital in Oxford , UK , studied the treatments given to all 109 patients managed during that month on whom a diagnosis had been reached . Medical sources ( including data bases ) were then search ed for r and omised controlled trial ( RCT ) evidence that the treatments were effective . The 109 primary treatments were then classified : 82 % were evidence based ( ie , there was RCT support [ 53 % ] or unanimity on the team about the existence of convincing non-experimental evidence [ 29 % ] ) . This study , which needs to be repeated in other clinical setting s and for other disciplines , suggests that earlier pessimism over the extent to which evidence -based medicine is already practised is misplaced OBJECTIVE The purpose of this study was to investigate the safety and efficacy of risperidone in the treatment of schizophrenic patients and determine its optimal dose . METHOD This double-blind study included 388 schizophrenic patients drawn from 20 sites in the United States . Patients were r and omly assigned to 8 weeks ' treatment with placebo , one of four doses of risperidone ( 2 , 6 , 10 , or 16 mg ) , or 20 mg of haloperidol daily . RESULTS Clinical improvement ( 20 % reduction in total scores on the Positive and Negative Syndrome Scale for Schizophrenia ) at the study end point was shown by 35 % of the patients receiving 2 mg of risperidone , 57 % receiving 6 mg , 40 % receiving 10 mg , and 51 % receiving 16 mg ; and by 30 % receiving haloperidol and 22 % receiving placebo . Statistically significant differences in clinical improvement were found between 6 and 16 mg of risperidone versus placebo and versus haloperidol . Positive symptom scores were significantly lower after 6 , 10 , and 16 mg of risperidone and 20 mg of haloperidol than placebo ; negative symptom scores , however , were reduced significantly , compared with placebo , only after 6 and 16 mg of risperidone . The incidence of extra-pyramidal side effects ( measured by the Extrapyramidal Symptom Rating Scale ) was significantly higher in patients treated with 16 mg of risperidone or 20 mg of haloperidol than placebo . The results indicate that the optimal daily dose of risperidone for most schizophrenic patients in this study was 6 mg ; this dose was as effective as 16 mg , and the incidence of extrapyramidal symptoms in patients receiving 6 mg of risperidone was no higher than that in patients receiving placebo . CONCLUSIONS Risperidone is a safe antipsychotic that is effective against both the positive and negative symptoms of schizophrenia |
12,958 | 25,692,403 | Cognitive behavioural therapy is an effective treatment for childhood and adolescent anxiety disorders ; however , the evidence suggesting that CBT is more effective than active controls or TAU or medication at follow-up , is limited and inconclusive | BACKGROUND A previous Cochrane review ( James 2005 ) showed that cognitive behavioural therapy ( CBT ) was effective in treating childhood anxiety disorders ; however , questions remain regarding ( 1 ) the relative efficacy of CBT versus non-CBT active treatments ; ( 2 ) the relative efficacy of CBT versus medication and the combination of CBT and medication versus placebo ; and ( 3 ) the long-term effects of CBT .
OBJECTIVES To examine ( 1 ) whether CBT is an effective treatment for childhood and adolescent anxiety disorders in comparison with ( a ) wait-list controls ; ( b ) active non-CBT treatments ( i.e. psychological placebo , bibliotherapy and treatment as usual ( TAU ) ) ; and ( c ) medication and the combination of medication and CBT versus placebo ; and ( 2 ) the long-term effects of CBT . | OBJECTIVE To evaluate course and outcome of DSM-III-R anxiety disorders prospect ively in clinical ly referred children . METHOD Children were blindly and repeatedly assessed with a structured diagnostic interview over a 3- to 4-year period to determine recovery from anxiety disorder and development of new psychiatric disorders . Both psychopathological ( attention-deficit hyperactivity disorder , n = 50 ) and never psychiatrically ill ( NPI , n = 83 ) controls served as comparison groups for children with anxiety disorders ( n = 84 ) . RESULTS The majority of children ( 82 % ) were free from their intake anxiety disorders by the end of the follow-up . Relapse of these anxiety disorders after remission was rare ( 8 % ) . During follow-up , anxious children were more likely to develop new psychiatric disorders ( 30 % ) , primarily new anxiety disorders ( 16 % ) , than were NPI children ( 11 % and 2 % , respectively ) , but not psychopathological controls ( 42 % and 10 % , respectively ) . CONCLUSIONS Overall , results suggest a favorable outcome with respect to diagnostic status for clinical ly referred children with anxiety disorders . However , these children may be at risk for new psychiatric disorders over time Background Although literature provides support for cognitive behavioral therapy ( CBT ) as an efficacious intervention for social phobia , more research is needed to improve treatments for children . Methods Forty four Caucasian children ( ages 8 - 14 ) meeting diagnostic criteria of social phobia according to the Diagnostic and Statistical Manual of Mental Disorders ( 4th ed . ; APA , 1994 ) were r and omly allocated to either a newly developed CBT program focusing on cognition according to the model of Clark and Wells ( n = 21 ) or a wait-list control group ( n = 23 ) . The primary outcome measure was clinical improvement . Secondary outcomes included improvements in anxiety coping , dysfunctional cognitions , interaction frequency and comorbid symptoms . Outcome measures included child report and clinican completed measures as well as a diagnostic interview . Results Significant differences between treatment participants ( 4 dropouts ) and controls ( 2 dropouts ) were observed at post test on the German version of the Social Phobia and Anxiety Inventory for Children . Furthermore , in the treatment group , significantly more children were free of diagnosis than in wait-list group at post-test . Additional child completed and clinician completed measures support the results . Discussion The study is a first step towards investigating whether CBT focusing on cognition is efficacious in treating children with social phobia . Future research will need to compare this treatment to an active treatment group . There remain the questions of whether the effect of the treatment is specific to the disorder and whether the underlying theoretical model is adequate . Conclusion Preliminary support is provided for the efficacy of the cognitive behavioral treatment focusing on cognition in socially phobic children . Active comparators should be established with other evidence -based CBT programs for anxiety disorders , which differ significantly in their dosage and type of cognitive interventions from those of the manual under evaluation ( e.g. Coping Cat ) Abstract Objective To examine the extent and nature of outcome reporting bias in a broad cohort of published r and omised trials . Design Retrospective review of publications and follow up survey of authors . Cohort All journal articles of r and omised trials indexed in PubMed whose primary publication appeared in December 2000 . Main outcome measures Prevalence of incompletely reported outcomes per trial ; reasons for not reporting outcomes ; association between completeness of reporting and statistical significance . Results 519 trials with 553 publications and 10 557 outcomes were identified . Survey responders ( response rate 69 % ) provided information on unreported outcomes but were often unreliable — for 32 % of those who denied the existence of such outcomes there was evidence to the contrary in their publications . On average , over 20 % of the outcomes measured in a parallel group trial were incompletely reported . Within a trial , such outcomes had a higher odds of being statistically non-significant compared with fully reported outcomes ( odds ratio 2.0 ( 95 % confidence interval 1.6 to 2.7 ) for efficacy outcomes ; 1.9 ( 1.1 to 3.5 ) for harm outcomes ) . The most commonly reported reasons for omitting efficacy outcomes included space constraints , lack of clinical importance , and lack of statistical significance . Conclusions Incomplete reporting of outcomes within published articles of r and omised trials is common and is associated with statistical non- significance . The medical literature therefore represents a selective and biased subset of study outcomes , and trial protocol s should be made publicly available This study evaluated the effectiveness of cognitive-behavioral treatment for childhood anxiety in a community clinic setting in Hong Kong , China . Forty-five clinical ly-referred children ( age 6 - 11 years ) were r and omly assigned to either a cognitive-behavioral treatment program or a waitlist-control condition . Children in the treatment condition showed significant reduction in anxiety symptoms-both statistically and clinical ly-whereas children in the waitlist condition did not . After the waitlist period was over , the control group also received the treatment program and showed a similar reduction in symptoms . For the full sample of 45 children , the effectiveness of the intervention was significant immediately after treatment and in 3- and 6-month follow-ups . In addition , children 's anxiety cognition and their ability to cope with anxiety-provoking situations fully mediated the treatment gains . These results offer empirical support for cognitive-behavioral treatment programs in a non-Western cultural context and plausible mediators for how cognitive-behavioral therapy works OBJECTIVE A pilot study to evaluate the efficacy of a cognitive-behavioral group therapy program for adolescents with social phobia , simplified both in terms of time and labor intensity from a previously studied program ( Social Effectiveness Therapy for Children and Adolescents ) to be more appropriate for a community outpatient psychiatric setting . METHOD Twelve adolescents with social phobia ( ages 13 - 18 ) , diagnosed by DSM-IV criteria and confirmed with Anxiety Disorders Interview Schedule for Children assessment , were r and omly assigned to treatment ( n=6 ) and waitlist ( n=6 ) groups . The waitlist group was subsequently treated , and results were included in the data analysis . Assessment s , including Anxiety Disorders Interview Schedule for Children interviews and self-report Social Phobia and Anxiety Inventory and Beck Depression Inventory II question naires , were performed at baseline and immediately after treatment or waitlist . RESULTS All subjects completed the treatment program . Compared with the waitlist group , treated subjects showed significantly greater improvement in both examiner-evaluated ( Anxiety Disorders Interview Schedule for Children ) and self-reported ( Social Phobia and Anxiety Inventory ) symptoms of social anxiety ( effect sizes [ d ] , 1.63 and 0.85 , respectively ) . No significant change was seen in Beck Depression Inventory II scores for treatment or waitlist groups . CONCLUSIONS This study provides support for the use of simplified cognitive-behavioral interventions for adolescents with social phobia that are practical for community psychiatric setting The study examined the shape of therapeutic alliance using latent growth curve modeling and data from multiple informants ( therapist , child , mother , father ) . Children ( n = 86 ) with anxiety disorders were r and omized to family-based cognitive-behavioral treatment ( FCBT ; N = 47 ) with exposure tasks or to family education , support , and attention ( FESA ; N = 39 ) . Children in FCBT engaged in exposure tasks in Sessions 9 - 16 , whereas FESA participants did not . Alliance growth curves of FCBT and FESA youths were compared to examine the impact of exposure tasks on the shape of the alliance ( between-subjects ) . Within FCBT , the shape of alliance prior to exposure tasks was compared with the shape of alliance following exposure tasks ( within-subjects ) . Therapist , child , mother , and father alliance ratings indicated significant growth in the alliance across treatment sessions . Initial alliance growth was steep and subsequently slowed over time , regardless of the use of exposure tasks . Data did not indicate a rupture in the therapeutic alliance following the introduction of in-session exposures . Results are discussed in relation to the processes , mediators , and ingredients of efficacious interventions as well as in terms of the dissemination of empirically supported treatments 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 BACKGROUND Promising evidence has emerged of clinical gains using guided self-help cognitive-behavioural therapy ( CBT ) for child anxiety and by involving parents in treatment ; however , the efficacy of guided parent-delivered CBT has not been systematic ally evaluated in UK primary and secondary setting s. AIMS To evaluate the efficacy of low-intensity guided parent-delivered CBT treatments for children with anxiety disorders . METHOD A total of 194 children presenting with a current anxiety disorder , whose primary carer did not meet criteria for a current anxiety disorder , were r and omly allocated to full guided parent-delivered CBT ( four face-to-face and four telephone sessions ) or brief guided parent-delivered CBT ( two face-to-face and two telephone sessions ) , or a wait-list control group ( trial registration : IS RCT N92977593 ) . Presence and severity of child primary anxiety disorder ( Anxiety Disorders Interview Schedule for DSM-IV , child/parent versions ) , improvement in child presentation of anxiety ( Clinical Global Impression - Improvement scale ) , and change in child anxiety symptoms ( Spence Children 's Anxiety Scale , child/parent version and Child Anxiety Impact scale , parent version ) were assessed at post-treatment and for those in the two active treatment groups , 6 months post-treatment . RESULTS Full guided parent-delivered CBT produced superior diagnostic outcomes compared with wait-list at post-treatment , whereas brief guided parent-delivered CBT did not : at post-treatment , 25 ( 50 % ) of those in the full guided CBT group had recovered from their primary diagnosis , compared with 16 ( 25 % ) of those on the wait-list ( relative risk ( RR ) 1.85 , 95 % CI 1.14 - 2.99 ) ; and in the brief guided CBT group , 18 participants ( 39 % ) had recovered from their primary diagnosis post-treatment ( RR = 1.56 , 95 % CI 0.89 - 2.74 ) . Level of therapist training and experience was unrelated to child outcome . CONCLUSIONS Full guided parent-delivered CBT is an effective and inexpensive first-line treatment for child anxiety Twenty-three preadolescent children ( ages 8 - 11 ) meeting criteria for social phobia were r and omly assigned to either a 3-week cognitive-behavioral group intervention or a wait-list control group . The intervention consisted of psychoeducation , cognitive strategies , and behavioral exposure . Outcome measures included diagnostic interview as well as parent and child report measures of anxiety and depression . Improvements were observed at posttest , with results stronger for parent report and interviewer ratings than for child self-report . At 3-week follow-up , children receiving the intervention demonstrated significant improvements on the majority of child , parent , and interviewer reports of social anxiety and related symptoms relative to wait-list participants . Preliminary support is provided for the utility of a brief intervention for preadolescent children with social phobia . Limitations and implication s for future research are discussed OBJECTIVE Most tests of cognitive behavioral therapy ( CBT ) for youth anxiety disorders have shown beneficial effects , but these have been efficacy trials with recruited youths treated by research er-employed therapists . One previous ( nonr and omized ) trial in community clinics found that CBT did not outperform usual care ( UC ) . The present study used a more stringent effectiveness design to test CBT versus UC in youths referred to community clinics , with all treatment provided by therapists employed in the clinics . METHOD A r and omized controlled trial methodology was used . Therapists were r and omized to training and supervision in the Coping Cat CBT program or UC . Forty-eight youths ( 56 % girls , 8 to 15 years of age , 38 % Caucasian , 33 % Latino , 15 % African-American ) diagnosed with DSM-IV anxiety disorders were r and omized to CBT or UC . RESULTS At the end of treatment more than half the youths no longer met criteria for their primary anxiety disorder , but the groups did not differ significantly on symptom ( e.g. , parent report , eta-square = 0.0001 ; child report , eta-square = 0.09 ; both differences favoring UC ) or diagnostic ( CBT , 66.7 % without primary diagnosis ; UC , 73.7 % ; odds ratio 0.71 ) outcomes . No differences were found with regard to outcomes of comorbid conditions , treatment duration , or costs . However , youths receiving CBT used fewer additional services than UC youths ( χ(2)(1 ) = 8.82 , p = .006 ) . CONCLUSIONS CBT did not produce better clinical outcomes than usual community clinic care . This initial test involved a relatively modest sample size ; more research is needed to clarify whether there are conditions under which CBT can produce better clinical outcomes than usual clinical care . CLINICAL TRIAL REGISTRY INFORMATION : Community Clinic Test of Youth Anxiety and Depression Study , URL : http:// clinical trials.gov , unique identifier : NCT01005836 This study examined secondary outcomes of a r and omized clinical trial that evaluated an individual cognitive-behavioral ( ICBT ) , family-based cognitive-behavioral ( FCBT ) , and family-based education , support and attention ( FESA ) treatment for anxious youth . Participants ( 161 ) were between 7 and 14 years ( M=10.27 ) of age and had a principal diagnosis of separation anxiety disorder , social phobia , and /or generalized anxiety disorder . Hierarchical linear modeling examined youth-reported depressive symptomatology and parent- and teacher-reported externalizing behavior and adaptive functioning at pretreatment , posttreatment , and 1-year follow-up . In general , youth in all treatments evidence d improvements in most domains , with improvements maintained at follow-up . Overall , gender and age did not moderate treatment outcomes . The results suggest that both child and family cognitive-behavioral therapy , and the family-based supportive approach used in this study , can be effective in addressing some of the associated symptoms and adaptive functioning deficits typically linked to anxiety in youth This study evaluated the relative efficacy of an exposure-based contingency management ( CM ) treatment condition and an exposure-based cognitive self-control ( SC ) treatment condition relative to an education support ( ES ) control condition for treating children with phobic disorders . Eighty-one children and their parents completed a 10-week treatment program in which children and parents were seen in separate treatment sessions with the therapist , followed by a brief conjoint meeting . Children in both the CM and SC conditions showed substantial improvement on all of the outcome measures . These gains were maintained at 3- , 6- , and 12-month follow-ups . Interestingly , children in the ES condition also showed comparable improvements at posttreatment and at 3- , 6- , and 12-month follow-ups . Implication s of the findings are discussed with respect to knowledge development and clinical practice Background : Separation anxiety disorder ( SAD ) is one of the earliest and most common mental disorders in childhood , and a strong predictor of adult psychopathology . Despite significant progress in psychotherapy research on childhood anxiety disorders , no r and omized controlled trial has been conducted with a disorder-specific treatment program for young children suffering from SAD . Methods : Forty-three children ( ages 5–7 ) with SAD and their parents were assigned to either a 16-session disorder-specific SAD treatment program including parent training and classical cognitive-behavioral therapy ( CBT ) components , or to a 12-week waiting list group . Categorical and /or continuous data for anxiety , impairment/distress and quality of life were collected at baseline , after treatment/waiting list condition , and at a 4-week follow-up . Results : Intention-to-treat analyses indicate that 76.19 % of children allocated to the treatment group definitively no longer fulfilled DSM-IV criteria for SAD at follow-up , compared to 13.64 % in the waiting list group . Between 91 and 100 % of children rated themselves or were rated by their father , mother or therapist as very much or much improved on the global success rating immediately after treatment . Results indicated large time by treatment condition interaction effect sizes ( d = 0.98–1.41 ) across informants for reduction of distress/avoidance in separation situations after the test for the treatment condition . Further , parents reported significant improvements in impairment/distress in the child ’s major life domains and the child ’s quality of life . Treatment gains were maintained at the 4-week follow-up assessment . Conclusions : Results indicate the short-term efficacy of a disorder-specific treatment approach for SAD , and are among the first to indicate that CBT programs work with young children OBJECTIVE Test changes in ( a ) coping efficacy and ( b ) anxious self-talk as potential mediators of treatment gains at 3-month follow-up in the Child/Adolescent Anxiety Multimodal Treatment Study ( CAMS ) . METHOD Participants were 488 youth ( ages 7 - 17 ; 50.4 % male ) r and omized to cognitive-behavioral therapy ( CBT ; Coping cat program ) , pharmacotherapy ( sertraline ) , their combination , or pill placebo . Participants met Diagnostic and Statistical Manual for Mental Disorders-Fourth Edition ( DSM-IV ) criteria for generalized anxiety disorder , social phobia , and /or separation anxiety disorder . Coping efficacy ( reported ability to manage anxiety provoking situations ) was measured by youth and parent reports on the Coping Question naire , and anxious self-talk was measured by youth report on the Negative Affectivity Self-Statement Question naire . Outcome was measured using the Pediatric Anxiety Rating Scale ( completed by Independent Evaluators blind to condition ) . For temporal precedence , residualized treatment gains were assessed at 3-month follow-up . RESULTS Residualized gains in coping efficacy mediated gains in the CBT , sertraline , and combination conditions . In the combination condition , some unique effect of treatment remained . Treatment assignment was not associated with a reduction in anxious self-talk , nor did anxious self-talk predict changes in anxiety symptoms . CONCLUSIONS The findings suggest that improvements in coping efficacy are a mediator of treatment gains . Anxious self-talk did not emerge as a mediator Objective To compare the relative long-term benefit of family-focused cognitive behavioral therapy ( FCBT ) and child-focused cognitive behavioral therapy ( CCBT ) for child anxiety disorders at a 1-year follow-up . Method Thirty-five children ( 6–3 years old ) r and omly assigned to 12–16 sessions of family-focused CBT ( FCBT ) or child-focused CBT ( CCBT ) participated in a 1-year follow-up assessment . Independent evaluators , parents , and children rated anxiety and parental intrusiveness . All were blind to treatment condition and study hypotheses . Results Children assigned to FCBT had lower anxiety scores than children assigned to CCBT on follow-up diagnostician- and parent-report scores , but not child-report scores . Exploratory analyses suggested the advantage of FCBT over CCBT may have been evident more for early adolescents than for younger children and that reductions in parental intrusiveness may have mediated the treatment effect . Conclusion FCBT may yield a stronger treatment effect than CCBT that lasts for at least 1 year , although the lack of consistency across informants necessitates a circumspect view of the findings . The potential moderating and mediating effects considered in this study offer interesting avenues for further study This r and omized clinical trial compared the relative efficacy of individual ( child ) cognitive-behavioral therapy ( ICBT ) , family cognitive-behavioral therapy ( FCBT ) , and a family-based education/support/ attention ( FESA ) active control for treating anxiety disordered youth ages 7 - 14 years ( M = 10.27 ) . Youth ( N = 161 ; 44 % female ; 85 % Caucasian , 9 % African American , 3 % Hispanic , 3 % other/mixed ) with a principal diagnosis of separation anxiety disorder , social phobia , or generalized anxiety disorder and their parents participated . Outcome analyses were conducted using hierarchical linear models on the intent-to-treat sample at posttreatment and 1-year follow-up using diagnostic severity , child self-reports , parent reports , and teacher reports . Chi-square analyses were also conducted on diagnostic status at post and 1-year follow-up . Children evidence d treatment gains in all conditions , although FCBT and ICBT were superior to FESA in reducing the presence and principality of the principal anxiety disorder , and ICBT outperformed FCBT and FESA on teacher reports of child anxiety . Treatment gains , when found , were maintained at 1-year follow-up . FCBT outperformed ICBT when both parents had an anxiety disorder . Implication s for treatment and suggestions for research are discussed Acceptance and commitment therapy ( ACT ) has a small but growing data base of support . One hundred and one heterogeneous out patients reporting moderate to severe levels of anxiety or depression were r and omly assigned to traditional cognitive therapy ( CT ) or to ACT . To maximize external validity , the authors utilized very minimal exclusion criteria . Participants receiving CT and ACT evidence d large , equivalent improvements in depression , anxiety , functioning difficulties , quality of life , life satisfaction , and clinician-rated functioning . Whereas improvements were equivalent across the two groups , the mechanisms of action appeared to differ . Changes in “ observing ” and “ describing ” one 's experiences appeared to mediate outcomes for the CT group relative to the ACT group , whereas “ experiential avoidance , ” “ acting with awareness , ” and “ acceptance ” mediated outcomes for the ACT group . Overall , the results suggest that ACT is a viable and disseminable treatment , the effectiveness of which appears equivalent to that of CT , even as its mechanisms appear to be distinct CONTEXT Epidemiological findings demonstrating an increased risk for individuals with social anxiety disorder ( SAD ) to develop depression have been challenged by discrepant findings from prospect i ve longitudinal examinations in childhood and early adolescence . OBJECTIVES To examine patterns of SAD incidence , the consistency of associations of SAD with subsequent depression , and distal and proximal predictors for subsequent depression . DESIGN Face-to-face , 10-year prospect i ve longitudinal and family study of up to 4 waves . The DSM-IV Munich-Composite International Diagnostic Interview was administered by clinical ly trained interviewers . SETTING Community sample in Munich . PARTICIPANTS Three thous and twenty-one individuals aged 14 to 24 years at baseline and 21 to 34 years at follow-up . MAIN OUTCOME MEASURES Cumulative incidence of SAD and depression ( major depressive episode or dysthymia ) . RESULTS Cumulative incidence for SAD was 11.0 % ; for depression , 27.0 % . St and ardized person-years of incidence for SAD were highest for those aged 10 to 19 years ( 0.72 % ) and were low before ( 0.20 % ) and after ( 0.19 % ) that age range . Depression incidence was different , characterized by delayed and continued high rates . Social anxiety disorder was consistently associated with subsequent depression , independent of age at onset for SAD ( relative risk range , 1.49 - 1.85 , controlling for age and sex ) . Crude Cox regressions showed significant distal ( eg , parental anxiety or depression , behavioral inhibition ) and proximal SAD characteristics ( eg , severity measures , persistence ) as predictors . Most associations were attenuated in multiple models , leaving behavioral inhibition ( hazard ratio , 1.30 [ 95 % confidence interval , 1.04 - 1.62 ; P = .02 ] ) and , less consistently , panic ( hazard ratio , 1.85 [ 95 % confidence interval , 1.08 - 3.18 ; P = .03 ] ) as the remaining significant predictors . CONCLUSIONS Social anxiety disorder is an early , adolescent-onset disorder related to a substantially and consistently increased risk for subsequent depression . The demonstration of proximal and particularly distal predictors for increased depression risks requires further exploration to identify their moderator or mediator role . Along with previous evidence that comorbid SAD is associated with a more malignant course and character of depression , these results call for targeted prevention with the aim of reducing the burden of SAD and its consequences Anxiety is common among adolescents with autism spectrum disorders ( ASD ) and may amplify the core social disability , thus necessitating combined treatment approaches . This pilot , r and omized controlled trial evaluated the feasibility and preliminary outcomes of the Multimodal Anxiety and Social Skills Intervention ( MASSI ) program in a sample of 30 adolescents with ASD and anxiety symptoms of moderate or greater severity . The treatment was acceptable to families , subject adherence was high , and therapist fidelity was high . A 16 % improvement in ASD social impairment ( within-group effect size = 1.18 ) was observed on a parent-reported scale . Although anxiety symptoms declined by 26 % , the change was not statistically significant . These findings suggest MASSI is a feasible treatment program and further evaluation is warranted OBJECTIVE To evaluate changes in the trajectory of youth anxiety following the introduction of specific cognitive-behavior therapy ( CBT ) components : relaxation training , cognitive restructuring , and exposure tasks . METHOD Four hundred eighty-eight youths ages 7 - 17 years ( 50 % female ; 74 % ≤ 12 years ) were r and omly assigned to receive either CBT , sertraline ( SRT ) , their combination ( COMB ) , or pill placebo ( PBO ) as part of their participation in the Child/Adolescent Anxiety Multimodal Study ( CAMS ) . Youths in the CBT conditions were evaluated weekly by therapists using the Clinical Global Impression Scale-Severity ( CGI-S ; Guy , 1976 ) and the Children 's Global Assessment Scale ( CGAS ; Shaffer et al. , 1983 ) and every 4 weeks by blind independent evaluators ( IEs ) using the Pediatric Anxiety Ratings Scale ( PARS ; RUPP Anxiety Study Group , 2002 ) . Youths in SRT and PBO were included as controls . RESULTS Longitudinal discontinuity analyses indicated that the introduction of both cognitive restructuring ( e.g. , changing self-talk ) and exposure tasks significantly accelerated the rate of progress on measures of symptom severity and global functioning moving forward in treatment ; the introduction of relaxation training had limited impact . Counter to expectations , no strategy altered the rate of progress in the specific domain of anxiety that it was intended to target ( i.e. , somatic symptoms , anxious self-talk , avoidance behavior ) . CONCLUSIONS Findings support CBT theory and suggest that cognitive restructuring and exposure tasks each make substantial contributions to improvement in youth anxiety . Implication s for future research are discussed . ( PsycINFO Data base Background There is increasing public and professional awareness of autism spectrum disorders with early recognition , diagnosis and interventions that are known to improve prognosis . Poor knowledge about childhood autism among paediatric and psychiatric nurses who are members of multidisciplinary teams that care for such children may be a major barrier to early interventions that could improve quality of life and prognosis in childhood autism . Factors that influence knowledge about childhood autism among these nurses are not known . This study assessed knowledge about childhood autism among paediatric and psychiatric nurses in Ebonyi state , Nigeria and determined the factors that could be influencing such knowledge . Methods Forty specialist paediatric and forty psychiatric nurses , making a total sample of eighty , were r and omly selected from all the health care facilities in Ebonyi state , Nigeria . A socio-demographic question naire and knowledge about childhood autism among health workers ( KCAHW ) question naire were administered to them and the study was a point survey . Results The total mean score on the KCAHW question naire among the nurses that participated in the study was 12.56 ± 3.23 out of a total of 19 possible . The mean score for the paediatric nurses was 11.78 ± 3.64 while psychiatric nurses had mean score of 13.35 ± 2.58 . The mean scores in Domain 1 were 6.17 ± 1.75 for the paediatric nurses and 6.52 ± 1.43 for the psychiatric nurses . The mean scores in Domain 2 were 0.65 ± 0.48 for the paediatric nurses and 0.80 ± 0.41 for the psychiatric nurses . Domain 3 showed mean scores of 1.97 ± 1.25 for the paediatric nurses while psychiatric nurses scored 2.62 ± 1.23 . Domain 4 yielded the mean scores of 2.97 ± 1.54 and 3.42 ± 0.98 for the paediatric and psychiatric nurses respectively . There was significant relationship between the total mean score on the KCAHW question naire for the two groups and the area of specialisation of the nurses ( t = -2.23 , df = 78 , p = 0.03 ) and there was also significant relationship between previous involvement in managing children with childhood autism as a specialist paediatric or psychiatric nurse and the total mean score on the KCAHW question naire ( t = 6.90 , df = 78 , p = 0.00 ) . Conclusion The scores reflect deficits in knowledge about childhood autism among the study cohorts . Paediatric and psychiatric nurses as members of multidisciplinary teams that care for children with childhood autism are expected to provide holistic care and adequate counselling to the families of these children . Unfortunately in this environment , they are not fully equipped with enough knowledge about childhood autism . Education on childhood autism is therefore needed and can be provided through continuing medical education and emphasizing childhood autism in their training curriculum . This will enhance early identification and diagnosis of childhood autism with early interventions that are known to improve prognosis The Queensl and Early Intervention and Prevention of Anxiety Project evaluated a child- and family-focused group intervention for preventing anxiety problems in children . This article reports on 12- and 24-month follow-up data to previously reported outcomes at posttreatment and at 6-month follow-up . A total of 1,786 7- to 14-year-olds were screened for anxiety problems using teacher nominations and children 's self-report . After diagnostic interviews , 128 children were selected and assigned to either a 10-week school-based child- and parent-focused psychosocial intervention or a monitoring group . Both groups showed improvements immediately at postintervention and at 6-month follow-up ; the improvement was maintained in the intervention group only reducing the rate of existing anxiety disorder and preventing the onset of new anxiety disorders . At 12 months , the groups converged , but the superiority of the intervention group was evident again at 2-year follow-up . Severity of pretreatment diagnoses , gender , and parental anxiety predicted poor initial response to intervention , whereas pretreatment severity was the only predictor of chronicity at 24 months . Overall , follow-up results show that a brief school-based intervention for children can produce durable reductions in anxiety problems OBJECTIVE Despite recent advances , there are still no interventions that have been developed for the specific treatment of young children who have anxiety disorders . This study examined the impact of a new , cognitive-behaviorally based parenting intervention on anxiety symptoms . METHOD Families of 74 anxious children ( aged 9 years or less ) took part in a r and omized controlled trial , which compared the new 10-session , group-format intervention with a wait-list control condition . Outcome measures included blinded diagnostic interview and self-reports from parents and children . RESULTS Intention-to-treat analyses indicated that children whose parent(s ) received the intervention were significantly less anxious at the end of the study than those in the control condition . Specifically , 57 % of those receiving the new intervention were free of their primary disorder , compared with 15 % in the control condition . Moreover , 32 % of treated children were free of any anxiety diagnosis at the end of the treatment period , compared with 6 % of those in the control group . Treatment gains were maintained at 12-month follow-up . CONCLUSIONS This new parenting-based intervention may represent an advance in the treatment of this previously neglected group OBJECTIVE Research has examined the effects of parental psychopathology , family functioning , and caregiver strain on treatment response in anxious youths . Although these variables have shown individual links to youth treatment response , theoretical models for their combined effects remain unexplored . This study tested the hypothesis that improvements in family functioning and reductions in caregiver strain explained the effects of parental psychopathology on youth treatment outcome in an anxiety treatment trial . METHOD A multiple mediation technique was used to test the proposed model across independent evaluator ( IE ) , parent , and youth informants in 488 youths , aged 7 - 17 years ( 50 % female ; mean age = 10.7 ) meeting Diagnostic and Statistical Manual of Mental Disorders criteria for social phobia , separation anxiety , and /or generalized anxiety disorder . Youths were r and omized to receive 12 weeks of cognitive-behavioral treatment ( Coping Cat ) , medication ( sertraline ) , their combination , or a pill placebo . At pre- and posttreatment , parents completed self-report measures of global psychopathology symptoms , family functioning , and caregiver strain ; parents , youths , and IEs rated youths ' anxiety symptom severity . RESULTS Changes in family functioning and caregiver strain jointly explained relations between parental psychopathology and reductions in youth anxiety . Specifically , across IE and parent informants , families with higher pretreatment parental psychopathology showed more improvement in family functioning and caregiver strain , which in turn predicted greater youth anxiety reductions . Further , higher pretreatment parental psychopathology predicted greater caregiver strain reductions and , in turn , greater youth anxiety reductions , based on youths ' reports of their own anxiety . CONCLUSIONS Findings suggest that improvements in family functioning and reductions in caregiver strain can influence treatment outcomes for anxious youths , especially among youths with more distressed parents OBJECTIVES This study examined ( 1 ) the effect of a cognitive-behavioral group intervention on anxiety , depression , and coping strategies in school-age children ( aged 7 - 12 years ) with Axis I anxiety disorders ; and ( 2 ) the effect of parental involvement on treatment outcomes . METHOD Parents and children ( N = 62 ) were r and omly assigned to one of three 12-week treatment conditions : parent and child intervention , child-only intervention , and parent-only intervention . Child anxiety , depression , and coping strategies were assessed before and after treatment . RESULTS All treatment groups reported fewer symptoms of anxiety and depression posttreatment and changes in their use of coping strategies . Children in the parent and child intervention used more active coping strategies posttreatment compared with children in the other 2 treatment conditions . Parents in this treatment condition reported a significantly greater improvement in their children 's emotional well-being than parents in the other treatment conditions . CONCLUSIONS Cognitive-behavioral group interventions reduced symptoms of anxiety and depression in school-age children with anxiety disorders . Concurrent parental involvement enhanced the effect on coping strategies . Further investigation is needed to corroborate the effectiveness of such short-term interventions and the maintenance of treatment effects Undertook an evaluation of a cognitive-behavioral group family-based intervention for childhood anxiety disorders in Brisbane , Australia . The treatment aim ed to provide children and their families with skills in the management of anxiety and avoidance , problem solving , and mutual family support . Children ( n = 60 ) ranging from 7 to 14 years old who fulfilled diagnostic criteria for separation anxiety , overanxious disorder , or social phobia were r and omly allocated to 3 treatment conditions : group cognitive-behavioral therapy ( GROUP-CBT ) , group cognitive-behavioral therapy plus family management ( GROUP-FAM ) , and wait list ( WL ) . The effectiveness of the interventions was evaluated at posttreatment and 12-month follow-up . Results indicated that across treatment conditions , 64.8 % of children no longer fulfilled diagnostic criteria for an anxiety disorder in comparison with 25.2 % of children on the wait list . At 12-month FU , 64.5 % of children in the GROUP-CBT group and 84.8 % of children in the GROUP-FAM group were diagnosis free . Comparisons of children receiving GROUP-CBT with those receiving GROUP-FAM on self-report measures and clinician ratings indicated marginal added benefits from GROUP-FAM treatment . Results show that CBT interventions for childhood anxiety disorders can be effectively administered in a group format An extensive and growing number of review s of the published literature demonstrate that health research publications have frequent deficiencies . Of particular concern are poor reports of r and omised trials , which make it difficult or impossible for readers to assess how the research was conducted , to evaluate the reliability of the findings , or to place them in the context of existing research evidence . As a result , published reports of trials often can not be used by clinicians to inform patient care or to inform public health policy , and the data can not be included in systematic review s. Reporting guidelines are design ed to identify the key information that research ers should include in a report of their research . We describe the history of reporting guidelines for r and omised trials culminating in the CONSORT Statement in 1996 . We detail the subsequent development and extension of CONSORT and consider related initiatives aim ed at improving the reliability of the medical research literature OBJECTIVE To determine the efficacy of fluoxetine , pill placebo , and Social Effectiveness Therapy for Children ( SET-C ) for children and adolescents with social phobia . METHOD Youths ages 7 to 17 were r and omly assigned to one of the treatment conditions . Outcome was evaluated using self-reports , parent ratings , independent evaluator ratings , and behavioral assessment . RESULTS Both fluoxetine and SET-C were more efficacious than placebo in reducing social distress and behavioral avoidance and increasing general functioning . SET-C was superior to fluoxetine on each of these measures and was the only treatment superior to placebo in terms of improving social skills , decreasing anxiety in specific social interactions , and enhancing ratings of social competence . Furthermore , whereas fluoxetine appears to exert maximum effect by 8 weeks , SET-C provides continued improvement through week 12 . CONCLUSIONS Both fluoxetine and SET-C are efficacious for social phobia , although SET-C appears to provide added benefit by enhancing social skills The purpose of this pilot study was to evaluate whether a modified version of the Coping Cat program could be effective in reducing anxiety in children with autism spectrum disorder ( ASD ) . Twenty-two children ( ages 8–14 ; IQ ≥ 70 ) with ASD and clinical ly significant anxiety were r and omly assigned to 16 sessions of the Coping Cat program ( cognitive-behavioral therapy ; CBT ) or a 16-week waitlist . Children in the CBT condition evidence d significantly larger reductions in anxiety than those in the waitlist . Treatment gains were largely maintained at two-month follow-up . Results provide preliminary evidence that a modified version of the Coping Cat program may be a feasible and effective program for reducing clinical ly significant levels of anxiety in children with high-functioning ASD This study evaluated the effectiveness of rational-emotive therapy and rational-emotive imagery . Fifty-nine junior high school students who volunteered to participate in treatment for interpersonal anxiety were r and omly assigned to rational-emotive therapy without imagery ( RET ) , rational-emotive therapy with imagery ( REI ) , relationship-oriented counseling ( ROC ) , and waiting-list control ( WLC ) groups . Groups met for seven 50-minute treatment sessions during a three-week period . Assessment s were conducted at pretreatment , posttreatment , and three-week follow-up . Both self-report and sociometric measures were used to evaluate treatment outcome . At post assessment , both the RET and REI groups were rated on sociometric measures as significantly less interpersonally anxious than the WLC group . Mean scores favored the RET and REI groups , but no significant differences between these groups and the ROC group were obtained . The self-report measure did not significantly differentiate between groups , but the REI group demonstrated significant pre- to follow-up changes . Both the RET and REI groups yielded greater reductions in irrational thinking than did the ROC and WLC groups . In addition , the pattern of the results supported the use of rational-emotive imagery as a component of rational-emotive therapy . The practical implication s of these findings are discussed OBJECTIVE The current trial examined whether a specific cognitive-behavioral treatment package was more efficacious in treating childhood anxiety disorders than a nonspecific support package . METHOD One hundred twelve children ( aged 7 - 16 years ) with a principal anxiety disorder were r and omly allocated to either a group cognitive-behavioral treatment ( CBT ) program or a control condition ( group support and attention [ GSA ] ) . RESULTS Overall , results showed that CBT was significantly more efficacious compared with the GSA condition : 68.6 % of children in the CBT condition did not meet diagnostic criteria for their principal anxiety diagnosis at 6-month follow-up compared with 45.5 % of the children in the GSA condition . The results of the child- and parent-completed measures indicated that , although mothers of CBT children reported significantly greater treatment gains than mothers of GSA children , children reported similar improvements across conditions . CONCLUSIONS Specific delivery of cognitive-behavioral skills is more efficacious in the treatment of childhood anxiety than a treatment that includes only nonspecific therapy factors OBJECTIVE To conduct a controlled group outcome investigation of the efficacy of cognitive-behavioral treatment for school phobia . METHOD Fifty-six children with school phobia were r and omly assigned to 12 weeks of cognitive-behavioral therapy or an attention-placebo control condition . Pre- and posttreatment school attendance , self-reported anxiety and depression , and diagnostic status were compared . RESULTS Both the experimental and control treatments were equally effective at returning children to school . Both treatments also were effective in reducing children 's anxiety and depressive symptoms . Follow-up revealed no differences between groups when the children reentered school the next school year . CONCLUSIONS Overall , results suggest that psychosocial treatments are effective at returning school-phobic children to school and that the highly structured cognitive-behavioral approach may not be superior to more traditional educational and supportive treatment methods The Queensl and Early Intervention and Prevention of Anxiety Project evaluated the effectiveness of a cognitive-behavioral and family-based group intervention for preventing the onset and development of anxiety problems in children . A total of 1,786 7- to 14-year-olds were screened for anxiety problems using teacher nominations and children 's self-report . After recruitment and diagnostic interviews , 128 children were selected and assigned to a 10-week school-based child- and parent-focused psychosocial intervention or to a monitoring group . Both groups showed improvements immediately postintervention . At 6 months follow-up , the improvement maintained in the intervention group only , reducing the rate of existing anxiety disorder and preventing the onset of new anxiety disorders . Overall , the results showed that anxiety problems and disorders identified using child and teacher reports can be successfully targeted through an early intervention school-based program OBJECTIVE To evaluate the feasibility and effectiveness of a school-based group cognitive-behavioral treatment ( CBT ) for anxiety disorders with African-American adolescents . METHOD Twelve adolescents ( mean age = 15.6 years ) with anxiety disorders were r and omly assigned to CBT ( n = 6 ) or a group attention-support control condition ( AS-Control ; n = 6 ) . Both groups met for 10 sessions in the same high school . Key treatment ingredients in CBT involved exposure , relaxation , social skills , and cognitive restructuring . Key ingredients in AS-Control involved therapist and peer support . At pre- and posttreatment , diagnostic interviews were conducted , and adolescents completed self-report measures of anxiety . RESULTS At posttreatment and among those who attended more than one treatment session , 3/4 adolescents in CBT no longer met diagnostic criteria for their primary anxiety disorder , compared with 1/5 in AS-Control . Clinician ratings of impairment and self-report levels of overall anxiety were significantly lower at posttreatment in CBT compared with AS-Control . Teenagers in both groups reported lower levels of social anxiety from pre- to posttreatment . CONCLUSIONS Findings support the feasibility of implementing a manual-based CBT in an urban school setting . Responder rates among African-American adolescents were similar to those found in studies with white youths Background : Children and adolescents who seek medical treatment for persistent physical distress often suffer from co‐occurring anxiety disorders . Treatment options for this impaired population are limited . This study tests the feasibility and potential efficacy of a cognitive‐behavioral intervention targeting pain and anxiety for youth with impairing functional physical symptoms and anxiety disorders presenting to pediatricians for medical care . Methods : Children and adolescents ( aged 8–16 ) experiencing somatic complaints , without an explanatory medical disorder ( i.e. , functional ) , were recruited from primary care and specialty ( gastroenterologists and cardiologists ) pediatricians . Forty children , primarily with gastrointestinal symptoms , who met criteria for a co‐occurring anxiety disorder , were r and omly assigned to a cognitive‐behavioral treatment addressing pain and anxiety , Treatment of Anxiety and Physical Symptoms ( TAPS ) , or to a waiting list control . Results : TAPS was found to be an acceptable treatment for this population and was superior to the waiting list condition . Eighty percent of children in TAPS were rated as treatment responders by independent evaluators compared with none of the controls . Overall , self‐ and parent ratings indicated reductions in children 's somatic discomfort and anxiety following intervention . TAPS participants maintained clinical gains 3 months following treatment . Conclusions : The study supports the feasibility and preliminary efficacy of a cognitive‐behavioral intervention targeting co‐occurring physical distress and anxiety in youth presenting for medical treatment . Such an approach has the potential to exert broad impact on children 's dysfunction and to minimize exposure to invasive , ineffective , and costly medical procedures and treatments . Depression and Anxiety , 2011 . © 2011 Wiley‐Liss , OBJECTIVE To evaluate the efficacy of a 4-week cognitive-behavioral treatment program for children who refuse to go to school . METHOD Thirty-four school-refusing children ( aged 5 to 15 years ) were r and omly assigned to a cognitive-behavioral treatment condition or a waiting-list control condition . Treatment consisted of individual child cognitive-behavioral therapy plus parent/teacher training in child behavior management skills . Measures taken before and after treatment included school attendance , child self-report of emotional distress and coping , caregiver reports on emotional and behavioral problems , and clinician ratings of global functioning . RESULTS Relative to waiting-list controls , children who received cognitive-behavioral therapy exhibited a significant improvement in school attendance . These children also improved on self-reports of fear , anxiety , depression , and coping . Significant improvements also occurred in relation to caregiver reports and clinician ratings . Maintenance of therapeutic gains was demonstrated at a 3-month follow-up assessment . CONCLUSIONS Cognitive-behavioral treatment of school refusal was efficacious and acceptable . The relative contributions of child therapy and parent/teacher training require further study OBJECTIVE To examine the efficacy of a developmentally appropriate parent-child cognitive behavioral therapy ( CBT ) protocol for anxiety disorders in children ages 4 - 7 years . METHOD DESIGN R and omized wait-list controlled trial . Conduct : Sixty-four children ( 53 % female , mean age 5.4 years , 80 % European American ) with anxiety disorders were r and omized to a parent-child CBT intervention ( n = 34 ) or a 6-month wait-list condition ( n = 30 ) . Children were assessed by interviewers blind to treatment assignment , using structured diagnostic interviews with parents , laboratory assessment s of behavioral inhibition , and parent question naires . ANALYSIS Chi-square analyses of outcome rates and linear and ordinal regression of repeated measures , examining time by intervention interactions . RESULTS The response rate ( much or very much improved on the Clinical Global Impression Scale for Anxiety ) among 57 completers was 69 % versus 32 % ( CBT vs. controls ) , p < .01 ; intent-to-treat : 59 % vs. 30 % , p = .016 . Treated children showed a significantly greater decrease in anxiety disorders ( effect size [ ES ] = .55 ) and increase in parent-rated coping ( ES = .69 ) than controls , as well as significantly better CGI improvement on social phobia/avoidant disorder ( ES = .95 ) , separation anxiety disorder ( ES = .82 ) , and specific phobia ( ES = .78 ) , but not on generalized anxiety disorder . Results on the Child Behavior Checklist Internalizing scale were not significant and were limited by low return rates . Treatment response was unrelated to age or parental anxiety but was negatively predicted by behavioral inhibition . Gains were maintained at 1-year follow-up . CONCLUSIONS Results suggest that developmentally modified parent-child CBT may show promise in 4- to 7-year-old children Cognitive behavior therapy delivered by trained clinicians has been shown to be an effective treatment for childhood anxiety . However , the prevalence of anxiety disorders in children and adolescents , combined with the practical and psychological obstacles that often prevent families from accessing professional help , mean that alternative ways of reaching prospect i ve clients must be explored . This pilot study aims to compare the relative efficacy of two different modes of delivering a family-focused , cognitive-behavioral intervention for children with an anxiety disorder . The two modalities compared were : a parent-delivered program ( bibliotherapy ) and a clinician-delivered program ( individual therapy ) . Twenty-seven children aged between 7 and 14 , together with their parents , were r and omly assigned to one of the two conditions listed above . Results at post-treatment showed a significant improvement for children in both treatment conditions in terms of diagnostic status , number of diagnoses and severity of primary diagnosis at follow-up . Children in the bibliotherapy condition demonstrated a significant improvement over time in terms of child- and parent-reported anxiety levels . No differences were found between the two treatment conditions on any outcome measure . These results were maintained at 3- and 6-month follow-up . Although a pilot study , these data suggest that a bibliotherapy format of the intervention described may have potential merit . The implication s for service delivery are discussed , as are the limitations of this research A family-based treatment for childhood anxiety was evaluated . Children ( n = 79 ) aged 7 to 14 who fulfilled diagnostic criteria for separation anxiety , overanxious disorder , or social phobia were r and omly allocated to 3 treatment conditions : cognitive-behavioral therapy ( CBT ) , CBT plus family management ( CBT + FAM ) , and waiting list . The effectiveness of the interventions was evaluated at posttreatment and at 6 and 12 months follow-up . The results indicated that across treatment conditions , 69.8 % of the children no longer fulfilled diagnostic criteria for an anxiety disorder , compared with 26 % of the waiting-list children . At the 12-month follow-up , 70.3 % of the children in the CBT group and 95.6 % of the children in the CBT + FAM group did not meet criteria . Comparisons of children receiving CBT with those receiving CBT + FAM on self-report measures and clinician ratings indicated added benefits from CBT + FAM treatment . Age and gender interacted with treatment condition , with younger children and female participants responding better to the CBT + FAM condition OBJECTIVE Psychiatric comorbidity is common in anxious children . The purpose of this study was to investigate the impact of comorbidity on treatment outcome in anxious children . METHOD Participants were 173 children between the ages of 8 and 13 years who met primary DSM-III-R/DSM-IV diagnoses of separation anxiety disorder , overanxious disorder/generalized anxiety disorder , or avoidant disorder/social phobia assessed by the Anxiety Disorders Interview Schedule for Children ( ADIS-C ) . The majority ( 79 % ) had at least one comorbid diagnosis . Participants were r and omly assigned to cognitive-behavioral therapy or waitlist . Group differences in ADIS-C diagnoses were compared after treatment . Multiple parent and child self-report measures were used to measure symptoms as well . RESULTS Pretreatment comorbidity was not associated with differences in treatment outcome : 68.4 % of noncomorbid participants and 70.6 % of comorbid participants were free of their primary diagnosis after treatment . Regarding parent and child self-report symptoms , multivariate analyses of variance revealed significant time ( treatment ) main effects , but no significant main effect for group ( comorbid status ) or time/group interaction . CONCLUSIONS The cognitive-behavioral treatment program was similarly effective in anxious children with and without comorbid disorders ; both groups showed clinical ly significant reductions in pretreatment diagnoses and symptoms OBJECTIVE This study compared 3 experimental conditions : wait-list , therapist-supported bibliotherapy , and individual therapy , in the treatment of child anxiety . METHOD Participants were 55 children ( 25 girls and 30 boys ) , aged 7 to 14 years diagnosed with an anxiety disorder , and their parents . Families were assigned using a modified r and om assignment process to 1 of the 3 conditions . The intervention evaluated in the 2 active treatment conditions was a family-focused , cognitive-behavioral program . RESULTS At posttreatment , participants in both treatment conditions had improved significantly on both diagnostic and question naire outcome measures compared with participants in the wait-list condition , with no differences demonstrated between the treatment conditions . Thus , at posttreatment , 0 % of children in the wait-list condition were anxiety diagnosis free , compared with 95 % in the therapist-supported bibliotherapy condition and 78.3 % in the individual therapy condition . There was no significant difference between diagnostic status at posttreatment between the 2 treatment conditions . Participants assigned to a treatment condition were reassessed at 3-month and 6-month follow-up . Treatment gains were maintained in both conditions across the follow-up period . CONCLUSION In light of the fact that more than 80 % of anxiety-disordered children never receive treatment , these data suggest that therapist-supported bibliotherapy represents a cost-effective means of reaching a greater number of anxious children A r and omized clinical trial evaluated the therapeutic efficacy of group cognitive-behavioral therapy ( GCBT ) versus a wait-list control ( WLC ) condition to treat anxiety disorders in children . Results indicated that GCBT , with concurrent parent sessions , was highly efficacious in producing and maintaining treatment gains . Children in GCBT showed substantial improvement on all the main outcome measures , and these gains were maintained at 3- , 6- , and 12-month follow-ups . Children in the WLC condition did not show improvements from the pre- to the postwait assessment point . These findings are discussed in terms of the need to continue to advance the development of practical , as well as conceptual , knowledge of efficacious treatment for anxiety disorders in children OBJECTIVE To evaluate a 12-week cognitive-behavioral treatment program for children with anxiety disorders and the additional value of a seven-session cognitive parent training program . METHOD Seventy-nine children with an anxiety disorder ( aged 7 - 18 years ) were r and omly assigned to a cognitive behavioral treatment condition or a wait-list control condition . Families in the active treatment condition were r and omly assigned to an additional seven-session cognitive parent training program . Semistructured diagnostic interviews were conducted with parents and children separately , before and after treatment and at 3 months follow-up . Question naires included child self-reports on anxiety and depression and parent reports on child 's anxiety and behavioral problems . RESULTS Children with anxiety disorders showed more treatment gains from cognitive-behavioral therapy than from a wait-list control condition . These results were substantial and significant in parent measures and with regard to diagnostic status , but not in child self-reports . In the active treatment condition , children improved on self-reported anxiety and depression , as well as on parent reports on their child 's anxiety problems . These results were equal for clinical ly referred and recruited children . Child self-reports decreased to the normal mean , whereas parents reported scores that were lower than before treatment but were still elevated from the normal means . No significant outcome differences were found between families with or without additional parent training . CONCLUSIONS Children with anxiety disorders profited from cognitive-behavioral therapy . Children improved equally whether or not additional parent training was offered BACKGROUND Children with autism spectrum disorders often present with comorbid anxiety disorders that cause significant functional impairment . This study tested a modular cognitive behavioral therapy ( CBT ) program for children with this profile . A st and ard CBT program was augmented with multiple treatment components design ed to accommo date or remediate the social and adaptive skill deficits of children with ASD that could pose barriers to anxiety reduction . METHOD Forty children ( 7 - 11 years old ) were r and omly assigned to 16 sessions of CBT or a 3-month waitlist ( 36 completed treatment or waitlist ) . Therapists worked with individual families . The CBT model emphasized behavioral experimentation , parent-training , and school consultation . Independent evaluators blind to treatment condition conducted structured diagnostic interviews and parents and children completed anxiety symptom checklists at baseline and posttreatment/postwaitlist . RESULTS In intent-to-treat analyses , 78.5 % of the CBT group met Clinical Global Impressions-Improvement scale criteria for positive treatment response at posttreatment , as compared to only 8.7 % of the waitlist group . CBT also outperformed the waitlist on diagnostic outcomes and parent reports of child anxiety , but not children 's self-reports . Treatment gains were maintained at 3-month follow-up . CONCLUSIONS The CBT manual employed in this study is one of the first adaptations of an evidence -based treatment for children with autism spectrum disorders . Remission of anxiety disorders appears to be an achievable goal among high-functioning children with autism Social anxiety disorder , whose onset peaks in adolescence , is associated with significant impairment . Despite the availability of effective treatments , few affected youth receive services . Transporting interventions into schools may circumvent barriers to treatment . The efficacy of a school-based intervention for social anxiety disorder was examined in a r and omized wait-list control trial of 35 adolescents ( 26 females ) . Independent evaluators , blind to treatment condition , evaluated participants at preintervention , postintervention , and 9 months later . Adolescents in the intervention group demonstrated significantly greater reductions than controls in social anxiety and avoidance , as well as significantly improved overall functioning . In addition , 67 % of treated subjects , compared to 6 % of wait-list participants , no longer met criteria for social phobia following treatment . Findings support the possible efficacy of school-based intervention for facilitating access to treatment for socially anxious adolescents BACKGROUND The aim of the study was to evaluate the effectiveness of a brief CBT intervention for anxiety with children diagnosed with Asperger syndrome ( AS ) . A second interest was to evaluate whether more intensive parent involvement would increase the child 's ability to manage anxiety outside of the clinic setting . METHODS Seventy-one children aged ten to twelve years were recruited to participate in the anxiety programme . All children were diagnosed with AS and the presence of anxiety symptoms was accepted on parent report via brief interview . Children were r and omly assigned to one of three conditions : intervention for child only , intervention for child and parent , wait-list control . RESULTS The two intervention groups demonstrated significant decreases in parent-reported anxiety symptoms at follow-up and a significant increase in the child 's ability to generate positive strategies in an anxiety-provoking situation . There were a number of significant differences between the two interventions to suggest parent involvement as beneficial . CONCLUSIONS The sample of children with AS in this study presented with a profile of anxiety similar to a sample of clinical ly diagnosed anxious children . The intervention was endorsed by parents as a useful programme for children diagnosed with Asperger syndrome and exhibiting anxiety symptoms , and active parent involvement enhanced the usefulness of the programme . Limitations of the study and future research are discussed OBJECTIVE Childhood anxiety disorders ( AD ) are prevalent , debilitating disorders . The most effective treatment approach for children less than 8 years old requires further investigation . The study 's primary objective was to compare 2 cognitive-behavioral therapy ( CBT ) group programs . CBT was delivered to children 5 to 7 years old and their parents ( child-parent ) or only to parents ( parent-only ) , whereas children attended group sessions but did not receive CBT . METHOD Using a prospect i ve , repeated measures , longitudinal study design , 77 children ( 29 male , mean age = 6.8 years ; SD = 0.8 year ) with AD and their parents participated in either a 12-week child-parent or parent-only CBT group treatment after a 3-month no-treatment wait-time . Well-vali date d treatment outcome measures were completed at 5 assessment time points : initial assessment , pretreatment , immediately posttreatment , 6 months , and 12 months posttreatment . A mixed models analysis was used to assess change in AD severity and global functioning improvements from baseline within each treatment and between treatments . RESULTS No significant changes were noted in child-parent or parent-only treatment during the 3-month no-treatment wait time . Both treatments saw significant improvements posttreatment and at longer-term follow-up with significant reductions in AD severity measured by clinician and parent report and increases in global functioning . Significantly greater improvements were observed in the child-parent compared to the parent-only treatment . CONCLUSION This study suggests that both parent-only and child-parent group CBT improves AD severity in children 5 to 7 years old . Study results suggest that involvement of both children and parents in treatment is more efficacious than working with parents alone In this study a psychosocial treatment for 47 Ss ( aged 9 - 13 years ) with anxiety disorders was investigated . A 16-session cognitive-behavioral treatment was compared with a wait-list condition . Outcome was evaluated using child self-report , parent report , teacher report , cognitive assessment , and behavioral observations . Pretreatment-posttreatment changes and maintenance of gains at 1-year follow-up were examined . Results revealed that many treated Ss were found to be without a diagnosis at posttest and at follow-up and to be within normal limits on many measures . The child 's perception of the therapeutic relationship and the therapist 's perception of parental involvement were measured but were not related to outcome . Discussion focuses on characteristics of effective child therapy and the need for further research on treatment components and alternative treatment methods OBJECTIVE To compare the effectiveness of three school-based interventions for anxious children : group cognitive-behavioral therapy ( CBT ) for children , group CBT for children plus parent training group , and no-treatment control . METHOD Students ( 7 - 11 years old ) in three elementary schools ( N = 453 ) were screened using the Multidimensional Anxiety Scale for Children and teacher nomination . Subsequently , 101 identified children and their parents completed the Anxiety Disorders Interview Schedule for DSM-IV , Child Version . Children with features or DSM-IV diagnoses of separation anxiety disorder , generalized anxiety disorder , and /or social phobia ( n = 61 ) were r and omized by school to one of three conditions . Active treatments were nine weekly sessions of either group CBT or group CBT plus concurrent parent training . RESULTS Clinician-report , child-report , and parent-report measures of child anxiety demonstrated significant benefits of CBT treatments over the no-treatment control group . Effect size was 0.58 for change in composite clinician severity rating , the primary outcome measure , favoring collapsed CBT conditions compared with control . In addition , several instruments showed significantly greater improvement in child anxiety for group CBT plus parent training over group CBT alone . CONCLUSIONS Both active CBT treatments were more effective than the no-treatment control condition in decreasing child anxiety symptoms and associated impairment . When parent training was combined with child group CBT , there were some additional benefits for the children Sixty-seven children ( ages 8 and 12 ) with social phobia were r and omized to either a behavioral treatment program design ed to enhance social skills and decrease social anxiety ( Social Effectiveness Therapy for Children , SET-C ) or an active , but nonspecific intervention ( Testbusters ) . Children treated with SET-C were significantly more improved across multiple dimensions , including enhanced social skill , reduced social fear and anxiety , decreased associated psychopathology , and increased social interaction . Furthermore , 67 % of the SET-C group participants did not meet diagnostic criteria for social phobia at posttreatment compared with 5 % of those in the Testbusters group . Treatment gains were maintained at 6-month follow-up . The results are discussed in terms of treatment of preadolescent children with social phobia and the durability of treatment effects Pretreatment attrition , the systematic self-exclusion of potential participants during the recruitment phase of a study , poses a significant threat to the external validity of r and omized clinical trials . Very little is known about the factors that contribute to pretreatment attrition , especially among families seeking treatment for a child . The current study assessed pretreatment attrition in a r and omized clinical trial of behavior therapy , fluoxetine , and placebo for child and adolescent social phobia . Reluctance toward medication treatment accounted for 44.7 % of study refusals and was disproportionately common among ethnic minority families . Parents were particularly worried about the potential for side effects or physical/psychological dependency upon the medication . Results are discussed in terms of the implication s for external validity in future psychopharmacological clinical trials The current study sought to evaluate the relative long-term efficacy of a modularized cognitive behavioral therapy ( CBT ) program for children with anxiety disorders . Twenty four children ( 5–12 years old ) r and omly assigned to modular CBT or a 3-month waitlist participated in a 1-year follow-up assessment . Independent evaluators blind to treatment condition conducted structured diagnostic interviews , and caregivers and children completed symptom checklists at pre- and post- , and 1 year follow-up assessment s. Analyses revealed that 71.4 % of children who received CBT demonstrated a positive treatment response 1 year following treatment , and 83.3 % were free of any anxiety diagnosis at 1 year follow-up . Analyses further revealed robust effects of intervention on diagnostic outcomes , caregiver- and child-report measures of anxiety at 1 year follow-up . Results provide evidence of an ongoing advantage on anxiety-specific outcomes for this modularized school-based CBT program 1 year post-treatment Conducted the 1st r and omized clinical trial evaluating the efficacy of the FRIENDS program , a family-based group cognitive-behavioral treatment ( FGCBT ) for anxious children . Children ( n = 71 ) ranging from 6 to 10 years of age who fulfilled diagnostic criteria for separation anxiety ( SAD ) , generalized anxiety disorder ( GAD ) , or social phobia ( SOP ) were r and omly allocated to FRIENDS or to a 10-week wait-list control group . The effectiveness of the intervention was evaluated at posttreatment and 12-month follow-up . Results indicated that 69 % of children who completed FGCBT were diagnosis-free , compared to 6 % of children completing the wait-list condition . At 12-month follow-up , 68 % of children were diagnosis-free . Beneficial treatment effects were also evident on the self-report measures completed by the children and their mothers . Parents and children reported high treatment satisfaction . Results suggest that FRIENDS is an effective treatment for clinical ly anxious children . Limitations of this study and directions for future research are discussed OBJECTIVES To examine the efficacy of cognitive-behavioral group therapy for adolescents ( CBGT-A ) in females with social phobia and the effect of this treatment on the risk for major depression . METHOD Female adolescents with social phobia ( N = 35 ) were r and omly assigned to treatment ( n = 12 ) or no treatment ( n = 23 ) groups . Assessment s were conducted at baseline , after treatment , and at a 1-year follow-up . RESULTS Eleven subjects completed treatment . Sixteen weeks of treatment produced a significant improvement in interference and reduction in symptoms of social anxiety . There was a significant reduction in the number of subjects meeting DSM-IV criteria for social phobia in the CBGT-A versus the untreated group ; however , at the 1-year follow-up there were no significant differences by treatment condition . There was also suggestive evidence that treatment of social phobia lowers the risk for relapse of major depression among those with a history of major depression . Combining social phobia and major depression as the outcome produced more robust treatment effects in the 1-year follow-up . CONCLUSIONS This pilot study provides evidence for a moderate short-term effect of CBGT-A for treating female adolescents suffering from social phobia and indicates that treatment of social phobia may result in a reduction of major depression This preliminary r and omized controlled trial ( RCT ) examines the feasibility of dismantling cognitive behavioral therapy ( CBT ) for childhood anxiety disorders . Fourteen children ( 10 girls ) ages 7 to 14 ( m = 10.2 ) with social phobia , generalized anxiety disorder , separation anxiety disorder , or panic disorder were r and omized to receive 6 sessions of either a ) the pre-exposure anxiety management strategies presented in traditional CBT , or b ) parent-coached exposure therapy . The sample was selected from a treatment seeking population and is representative of children in clinical setting s. Examination of fidelity ratings , dropouts , and satisfaction ratings indicated that the interventions were distinguishable , safe , and tolerable . The overall sample improved significantly with pre-post effect sizes generally in the large range for both conditions . Between-group effect sizes indicating greater improvement with parent-coached exposure therapy were moderate or large for ten of 12 variables ( i.e. , 0.53 to 1.52 ) . Re-evaluation after three months of open treatment suggested that the intervention emphasizing exposure early maintained its superiority while requiring fewer appointments We compared the effects of a 16-week Cognitive-Behavioral Therapy ( CBT ) program and a Social Recreational ( SR ) program on anxiety in children with Autism Spectrum Disorders ( ASD ) . Seventy children ( 9–16 years old ) were r and omly assigned to either of the programs ( nCBT = 36 ; nSR = 34 ) . Measures on child ’s anxiety using the Spence Child Anxiety Scale — Child ( SCAS-C ) and the Clinical Global Impression — Severity scale ( CGI-S ) were administered at pre- , post-treatment , and follow-ups ( 3- and 6-month ) . Children in both programs showed significantly lower levels of generalized anxiety and total anxiety symptoms at 6-month follow-up on SCAS-C. Clinician ratings on the CGI-S demonstrated an increase in the percentage of participants rated as “ Normal ” and “ Borderline ” for both programs . Findings from the present study suggest factors such as regular sessions in a structured setting , consistent therapists , social exposure and the use of autism-friendly strategies are important components of an effective framework in the management of anxiety in children and adolescents with ASD BACKGROUND Anxiety disorders are common psychiatric conditions affecting children and adolescents . Although cognitive behavioral therapy and selective serotonin-reuptake inhibitors have shown efficacy in treating these disorders , little is known about their relative or combined efficacy . METHODS In this r and omized , controlled trial , we assigned 488 children between the ages of 7 and 17 years who had a primary diagnosis of separation anxiety disorder , generalized anxiety disorder , or social phobia to receive 14 sessions of cognitive behavioral therapy , sertraline ( at a dose of up to 200 mg per day ) , a combination of sertraline and cognitive behavioral therapy , or a placebo drug for 12 weeks in a 2:2:2:1 ratio . We administered categorical and dimensional ratings of anxiety severity and impairment at baseline and at weeks 4 , 8 , and 12 . RESULTS The percentages of children who were rated as very much or much improved on the Clinician Global Impression-Improvement scale were 80.7 % for combination therapy ( P<0.001 ) , 59.7 % for cognitive behavioral therapy ( P<0.001 ) , and 54.9 % for sertraline ( P<0.001 ) ; all therapies were superior to placebo ( 23.7 % ) . Combination therapy was superior to both monotherapies ( P<0.001 ) . Results on the Pediatric Anxiety Rating Scale documented a similar magnitude and pattern of response ; combination therapy had a greater response than cognitive behavioral therapy , which was equivalent to sertraline , and all therapies were superior to placebo . Adverse events , including suicidal and homicidal ideation , were no more frequent in the sertraline group than in the placebo group . No child attempted suicide . There was less insomnia , fatigue , sedation , and restlessness associated with cognitive behavioral therapy than with sertraline . CONCLUSIONS Both cognitive behavioral therapy and sertraline reduced the severity of anxiety in children with anxiety disorders ; a combination of the two therapies had a superior response rate . ( Clinical Trials.gov number , NCT00052078 . BACKGROUND Anxiety disorders are often undetected and untreated in adolescents . This study evaluates the relative efficacy of a school-based , cognitive-behavioral intervention compared to an educational-supportive treatment for adolescents with social anxiety disorder . METHODS Thirty-six students ( 30 females ) , ages 14 to 16 , were r and omized to a 12-week specific intervention , Skills for Social and Academic Success ( SASS ) , or a credible attention control matched for structure and contact , conducted in school . RESULTS Independent evaluations and adolescent self-reports indicated significant reduction in social anxiety for SASS compared to the control group . Parent reports of their children 's social anxiety did not discriminate between treatments . In the specific intervention , 59 % , compared to 0 % in the control , no longer met criteria for social anxiety disorder following treatment . Superiority of the SASS intervention was maintained 6 months after treatment cessation . CONCLUSIONS The study provides evidence that intervention for social anxiety disorder that emphasizes exposure and social skills is efficacious . Results indicate that clinical improvement is sustained for at least 6 months , and that , overall , adolescents with social anxiety disorder do not respond to non-specific treatment . This investigation has public health implication s by demonstrating that effective interventions can be transported to non clinical setting Supplementing bibliotherapy with therapist-client communication has been shown to be an effective way of providing services to under-re source d and isolated communities . The current study examined the efficacy of supplementing bibliotherapy for child anxiety disorders with therapist-initiated telephone or email sessions , or with client-initiated contact in a r and omised trial using a waitlist control . Participants were 100 anxiety-disordered children and their parents from rural and remote communities . All treatment conditions result ed in improvement on self-report measures and clinician rated severity . Telephone sessions produced superior outcomes with 79 % of children being anxiety disorder free post-treatment compared with 33 % of email and 31 % of client-initiated participants . The results suggest that therapist supplemented bibliotherapy could provide an efficacious treatment option for families isolated from traditional treatment services Preliminary data are presented on the effectiveness of a universal school-based intervention for the prevention of anxiety symptoms in primary school children . A sample of 489 children ( aged 10 - 12 years ) were assigned to one of three intervention conditions : a psychologist-led preventive intervention , a teacher-led preventive intervention , or a usual care ( st and ard curriculum ) with monitoring condition . The intervention offered was the Friends for Children programme , a 12-session cognitive-behavioural intervention , originally based upon Kendall 's ( 1994 ) Coping Cat programme . Participants in both intervention conditions reported fewer symptoms of anxiety at post-intervention than participants in the usual care condition . These preliminary results suggest that universal programmes for childhood anxiety are promising intervention strategies that can be successfully delivered to a school-based population and integrated into the classroom curriculum OBJECTIVE To prospect ively examine psychosocial functioning in young adulthood for children and adolescents with anxiety disorders . METHOD This 8-year prospect i ve study compared psychosocial functioning in young adults ( mean age 22 years ) who had histories of early-onset anxiety disorders , comorbid anxiety and depressive disorders , or no history of psychiatric illness ( NPI ) . Follow-up interviews assessed subjects ' residential , educational , occupational , and marital status ; utilization of mental health services ; and psychological status RESULTS Anxious subjects without histories of depression were less likely than NPI controls to be living independently . Anxious-depressed subjects were less likely than controls to be working or in school ; more likely than purely anxious subjects to utilize mental health services ; and more likely than both anxious and control subjects to report psychological problems , most frequently depression . CONCLUSIONS Overall , results suggest that children with anxiety disorders are relatively well adjusted in young adulthood . However , a history of comorbid depression is prognostic of a more negative outcome The present study examined the efficacy of group cognitive-behavioral therapy ( CBT ) in the treatment of childhood anxiety disorders . Thirty high-anxious children ( aged 9 - 12 years ) were assigned to either ( a ) group CBT ( n = 10 ) , ( b ) a psychological placebo intervention ( i.e. , emotional disclosure [ ED ] ; n = 10 ) , or ( c ) a no-treatment control condition ( n = 10 ) . Therapy outcome measures ( i.e. , children 's self-report of anxiety disorders symptoms , depression , and trait anxiety ) were obtained three months before treatment , at pretreatment , and at posttreatment . Results showed that levels of psychopathological symptoms remained relatively stable during the three months preceding treatment . Most importantly , pretreatment-posttreatment comparisons indicated that CBT was superior to ED and the no-treatment control condition . That is , only in the CBT condition significant reductions of anxiety disorders symptoms , trait anxiety , and depression were observed . These findings can be taken as further evidence for the efficacy of CBT in the treatment of childhood anxiety disorders Ninety-four children ( aged 9 - 13 years ) with anxiety disorders were r and omly assigned to cognitive behavioral treatment or waiting-list control . Outcomes were evaluated using diagnostic status , child self-reports , parent and teacher reports , cognitive assessment and behavioral observation : maintenance was examined using 1-year follow-up data . Analyses of dependent measures indicated significant improvements over time , with the majority indicating greater gains for those receiving treatment . Treatment gains returned cases to within nondeviant limits ( i.e. , normative comparisons ) and were maintained at 1-year follow-up . Client age and comorbid status did not moderate outcomes . A preliminary examination of treatment segments suggested that the enactive exposure ( when it follows cognitive-educational training ) was an active force in beneficial change . Discussion includes suggestions for future research The effectiveness of in vivo exposure and vicarious exposure in reducing children 's phobic anxiety and avoidance of water was investigated . Forty-eight water phobic children between the ages of 3 and 8 yr were r and omly assigned to one of four groups : ( 1 ) in vivo exposure plus vicarious exposure ( IVVE ) ; ( 2 ) vicarious exposure ( VE ) ; ( 3 ) in vivo exposure ( IVE ) ; and ( 4 ) assessment only control . All subjects in the treatment groups received three individually administered treatment sessions . At the conclusion of treatment it was found that the IVE condition had produced statistically and clinical ly significant gains that had generalized to another situation involving water , and were largely maintained over a period of 3 months . In contrast , the VE condition did not lead to statistically greater treatment benefits than those observed in the control subjects . Furthermore , there was no significant difference between the IVVE condition and the IVE condition in their level of improvement from pre- to post-treatment . Hence , by post-treatment , vicarious exposure had not only failed to produce benefits when used on its own , but had also failed to enhance the benefits achieved through in vivo exposure . However , a tendency for the vicarious component to enhance the maintenance of treatment benefits was found at follow-up . The implication s of these findings are discussed Background The effectiveness of cognitive-behavioral treatment ( CBT ) in inner city schools , when delivered by novice CBT clinicians , and compared to usual care ( UC ) , is unknown . Objective This pilot study addressed this issue by comparing a modular CBT for anxiety disorders to UC in a sample of 32 volunteer youth ( mean age 10.28 years , 63 % female , 84 % African American ) seen in school-based mental health programs . Methods Youth were r and omly assigned to CBT ( n = 17 ) or UC ( n = 15 ) ; independent evaluators conducted diagnostic interviews with children and parents at pre- and post-intervention , and at a one-month follow-up . Results Based on intent-to-treat analyses , no differences were found in response rates between groups with 50 and 42 % of the children in CBT , compared to 46 and 57 % in UC no longer meeting criteria for an anxiety disorder at post-treatment and follow-up respectively . Similar improvements in global functioning were also found in both treatment groups . Baseline predictors of a positive treatment response included lower anxiety , fewer maladaptive thoughts , less exposure to urban hassles , and lower levels of parenting stress . Therapist use of more CBT session structure elements and greater competence in implementing these elements was also related to a positive treatment response . Conclusions Findings from this small pilot failed to show that CBT was superior to UC when delivered by school-based clinicians . Large scale comparative effectiveness trials are needed to determine whether CBT leads to superior clinical outcomes prior to dissemination Early identification and treatment of social anxiety disorder ( SAD ) is critical to prevent development of a chronic course of symptoms , persistent functional impairment , and progressive psychiatric comorbidity . A small but growing literature supports the effectiveness of cognitive behavior therapy ( CBT ) for anxiety disorders , including SAD , in adolescence . The present r and omized controlled trial evaluated the efficacy of group vs. individual CBT for adolescents with generalized SAD in relation to an educational/supportive psychotherapy that did not contain specific CBT elements . All three treatments were associated with significant reductions in symptoms and functional impairment , and in improved social skills . No differences between treatments emerged on measures of symptoms , but the CBT conditions demonstrated greater gains on behavioral measures . The implication s of the findings are discussed Seventy-two clinical ly anxious children , aged 7 to 14 years , were r and omly allocated to clinic-based , cognitive-behavior therapy , the same treatment partially delivered via the Internet , or a wait-list control ( WL ) . Children in the clinic and clinic-plus-Internet conditions showed significantly greater reductions in anxiety from pre- to posttreatment and were more likely to be free of their anxiety diagnoses , compared with the WL group . Improvements were maintained at 12-month follow-up for both therapy conditions , with minimal difference in outcomes between interventions . The Internet treatment content was highly acceptable to families , with minimal dropout and a high level of therapy compliance Few studies have reported long-term follow-up data in adults and even fewer in adolescents . The purpose of this work is to report on the longest follow-up assessment in the literature on treatments for adolescents with social phobia . A 5-year follow-up assessment was conducted with subjects who originally received either Cognitive Behavioral Group Therapy for Adolescents ( CBGT-A ) , Social Effectiveness Therapy for Adolescents -- Spanish version ( SET-Asv ) , or Intervención en Adolescentes con Fobia Social -- Treatment for Adolescents with Social Phobia ( IAFS ) in a controlled clinical trial . Twenty-three subjects completing the treatment conditions were available for the 5-year follow-up . Results demonstrate that subjects treated either with CBGT-A , SET-Asv and IAFS continued to maintain their gains after treatments were terminated . Either the CBGT-A , SET-Asv and IAFS can provide lasting effects to the majority of adolescents with social anxiety . Issues that may contribute to future research and clinical implication s are discussed Fifty children aged 7 - 14 years with a principal diagnosis of social phobia were r and omly assigned to either child-focused cognitive-behaviour therapy ( CBT ) , CBT plus parent involvement , or a wait list control ( WLC ) . The integrated CBT program involved intensive social skills training combined with grade d exposure and cognitive challenging . At posttreatment , significantly fewer children in the treatment conditions retained a clinical diagnosis of social phobia compared to the WLC condition . In comparison to the WLC , children in both CBT interventions showed significantly greater reductions in children 's social and general anxiety and a significant increase in parental ratings of child social skills performance . At 12-month follow-up , both treatment groups retained their improvement . There was a trend towards superior results when parents were involved in treatment , but this effect was not statistically significant OBJECTIVE The current study examined mediators and moderators of treatment response among children and adolescents ( ages 7 - 17 years ) with a primary diagnosis of social phobia . METHOD Participants were 88 youths participating in one of two r and omized controlled treatment trials of Social Effectiveness Therapy for Children . Potential mediators included changes in observer-rated social skill and child-reported loneliness after 12 weeks of Social Effectiveness Therapy for Children . Age and depressive symptoms were examined as potential moderators . RESULTS Loneliness scores and social effectiveness during a role-play task predicted changes in social anxiety and overall functioning at posttreatment . Changes in social anxiety were mediated by child-reported loneliness . Outcomes were not moderated by age or depressive symptoms . CONCLUSIONS Findings support the role of loneliness as an important mechanism of change during treatment for childhood social phobia Background In the Netherl and s , the prevalence of anxiety disorders is 20 % ; and children with anxiety are at increased risk for psychopathology throughout adulthood . Recently , a revised version of a cognitive behavioral therapy manualized program called ' Thinking + Doing = Daring ' ( TDD ) was developed for children between 8 and 12 years old with an anxiety disorder . The main aim of this project is to conduct a R and omized Controlled Trial ( RCT ) to evaluate the effectiveness of TDD . Methods / Design The CBT program will be tested with a RCT with 120 clinical ly anxious children ( 8 - 12 years old ) referred to one of three mental health care agencies . Children will be r and omly assigned to the experimental ( N = 60 , TDD ) or to the control condition ( N = 60 , treatment as usual ) . The primary outcome measure will be the child 's anxiety symptoms level . Secondary outcome measures will be externalizing ( e.g. aggression ) and internalizing problems ( e.g. depression ) . Two potential mediators of change will be examined in the current study : therapeutic alliance and parenting . Mother and child in both the experimental and control condition will be surveyed at baseline , post treatment and after 6 and 12 months ( follow-up ) . It is hypothesized that children in the experimental condition will show a stronger decrease in anxiety symptoms compared to children that receive treatment as usual . Moreover , we expect that a strong therapeutic alliance and decreases in parental control and rejection will contribute to treatment success . Discussion Early treatment for anxiety problems has the potential to not only result in anxiety reductions , but also to prevent future problems such as substance abuse and psychopathology throughout adulthood . Our results will be immediately relevant to practice , since we are partnering with ' real world ' community agencies . If the CBT program proves more effective than treatment as usual , it could be implemented in community mental health care agencies across the Netherl and s and beyond . Moreover , it has the potential to make treatment in these community setting s shorter , more efficient and therefore cost-effective . Trial registration : Nederl and s Trial Register |
12,959 | 25,538,786 | Results : Our findings propose that school-based programs can have long-term effects in a large target group .
They have remarkable consequences on health behaviors , but as there are some common limitations , their effects on anthropometric measures are not clear .
Due to the crucial role of parents in development of children 's behaviors , family-based interventions are reported to have successful effects in some aspects ; but selection bias and high dropout rate can confound their results .
Clinic-based interventions revealed favorable effects .
They include dietary or other lifestyle changes like increasing physical activity or behavior therapy .
It seems that a comprehensive intervention including diet and exercise are more practical .
When they have different design s , results are controversial .
Conclusion : We suggest that among different types of interventional programs , a multidisciplinary approach in schools in which children 's family are involved , can be the best and most sustainable approach for management of childhood obesity | Background : Childhood obesity is a global health problem with short- and long-term health consequences .
This systematic review presents a summary of the experiences on different family- , school- , and clinic-based interventions .
This can be related to this fact that children spend a considerable part of their time in school , and adopt some parts of lifestyle there . | Objectives To assess a 2-year family-based behavioural intervention programme against child obesity . Design Single-group pre- and post-intervention feasibility study . Setting Swedish paediatric outpatient care . Participants 26 obese children aged 8.3–12.0 years and their parents who had consented to actively participate in a 2-year intervention . Interventions 25 paediatric outpatient group sessions over a 2-year period with parallel groups for children and parents . The basis for the programme was a manual containing instructions for tutor-supervised group sessions with obese children and their parents . Primary and secondary outcome measures The primary outcome measure was change in st and ardised body mass index between baseline and after 36 months . The secondary outcome measures were change in the waist : height ratio , metabolic parameters and programme adherence . The participants were examined at baseline and after 3 , 12 and 24 months of therapy and at follow-up 12 months after completion of the programme . Results The primary outcome measure , st and ardised body mass index , declined from a mean of 3.3 ( 0.7 SD ) at baseline to 2.9 ( 0.7 SD ) ( p<0.001 ) at follow-up 12 months after completion of the programme . There was no change in the waist : height ratio . Biomedical markers of blood glucose metabolism and lipid status remained in the normal range . 96 % of the families completed the programme . Conclusions This feasibility study of a 2-year family-based behavioural intervention programme in paediatric outpatient care showed promising results with regard to further weight gain and programme adherence . These findings must be confirmed in a r and omised controlled trial with longer follow-up before the intervention programme can be implemented on a larger scale OBJECTIVE The objective was to compare targeting increased eating of healthy foods vs. reducing intake of high energy-dense foods within the context of a family-based behavioral weight control program . METHODS AND PROCEDURES Forty-one 8 - 12 year-old children > 85th BMI percentile were r and omly assigned to a 24-month family-based behavioral treatment that targeted increasing fruits and vegetables and low-fat dairy vs. reducing intake of high energy-dense foods . RESULTS Children in the increase healthy food group showed greater reduction in z BMI compared to children in the reduce high energy-dense food group at 12- ( -0.30 z BMI units vs. -0.15 z BMI units , P = 0.01 ) and 24- ( -0.36 z BMI units vs -0.13 z BMI units , P = 0.04 ) month follow-up . Parents in the increase healthy food group showed greater reductions in concern about child weight ( P = 0.007 ) , and these changes were associated with child z BMI change ( P = 0.008 ) . Children in the reduce high energy-dense group showed larger sustained reductions in high energy-dense foods ( P < 0.05 ) . Baseline levels of high energy-dense foods ( P < 0.05 ) , parent food restraint ( P = 0.01 ) , parent concern over parent weight ( P = 0.01 ) and parent acceptance of the child ( P < 0.05 ) moderated child z BMI change , with greater sustained reductions in z BMI for children in the increase healthy food group for each measure . Parent z BMI change followed the same pattern as child changes , and parent and child z BMI changes were correlated ( P < 0.001 ) . DISCUSSION Focusing on healthy food choices within an energy restricted diet may be useful in family-based weight control programs OBJECTIVE . The objective of this study was to determine whether a generalizable best- practice individualized behavioral intervention reduced BMI z score relative to st and ard dietetic care among overweight children . METHODS . The design consisted of an assessor-blinded , r and omized , controlled trial involving 134 overweight children ( 59 boys , 75 girls ; BMI ≥ 98th centile relative to United Kingdom 1990 reference data for children aged 5–11 years ) who were r and omly assigned to a best- practice behavioral program ( intervention ) or st and ard care ( control ) . The intervention used family-centered counseling and behavioral strategies to modify diet , physical activity , and sedentary behavior . BMI z score , weight , objective ly measured physical activity and sedentary behavior , fat distribution , quality of life , and height z score were recorded at baseline and at 6 and 12 months . RESULTS . The intervention had no significant effect relative to st and ard care on BMI z score from baseline to 6 months and 12 months . BMI z score decreased significantly in both groups from baseline to 6 and 12 months . For those who complied with treatment , there was a significantly smaller weight increase in those in the intervention group compared with control subjects from baseline to 6 months . There were significant between-group differences in favor of the intervention for changes in total physical activity , percentage of time spent in sedentary behavior , and light-intensity physical activity . CONCLUSIONS . A generalizable , best- practice individualized behavioral intervention had modest benefits on objective ly measured physical activity and sedentary behavior but no significant effect on BMI z score compared with st and ard care among overweight children . The modest magnitude of the benefits observed perhaps argues for a longer-term and more intense intervention , although such treatments may not be realistic for many health care systems Background In 2005 , we reported on the success of Comprehensive School Health ( CSH ) in improving diets , activity levels , and body weights . The successful program was recognized as a " best practice " and has inspired the development of the Alberta Project Promoting active Living and healthy Eating ( APPLE ) Schools . The project includes 10 schools , most of which are located in socioeconomically disadvantaged areas . The present study examines the effectiveness of a CSH program adopted from a " best practice " example in another setting by evaluating temporal changes in diets , activity levels and body weight . Methods In 2008 and 2010 , we surveyed grade 5 students from approximately 150 r and omly selected schools from the Canadian province of Alberta and students from 10 APPLE Schools . Students completed the Harvard Youth/Adolescent Food Frequency Question naire , questions on physical activity , and had their height and weight measured . Multilevel regression methods were used to analyze changes in diets , activity levels , and body weight between 2008 and 2010 . Results In 2010 relative to 2008 , students attending APPLE Schools were eating more fruits and vegetables , consuming fewer calories , were more physically active and were less likely obese . These changes contrasted changes observed among students elsewhere in the province . Conclusions These findings provide evidence on the effectiveness of CSH in improving health behaviors . They show that an example of " best practice " may lead to success in another setting . Herewith the study provides the evidence that investments for broader program implementation based on " best practice " are justified Background —The prevalence of obesity in both adults and children is increasing rapidly . Obesity in children is independently associated with arterial endothelial dysfunction and wall thickening , key early events in atherogenesis that precede plaque formation . Methods and Results —To evaluate the reversibility of obesity-related arterial dysfunction and carotid intima-media thickening by dietary and /or exercise intervention programs , 82 overweight children ( body mass index , 25±3 ) , 9 to 12 years of age , were r and omly assigned to dietary modification only or diet plus a supervised structured exercise program for 6 weeks and subsequently for 1 year . The prospect ively defined primary end points were ultrasound-derived arterial endothelial function ( endothelium-dependent dilation ) of the brachial artery and intima-media thickness of common carotid artery . At 6 weeks , both interventions were associated with decreased waist-hip ratio ( P < 0.02 ) and cholesterol level ( P < 0.05 ) as well as improved arterial endothelial function . Diet and exercise together were associated with a significantly greater improvement in endothelial function than diet alone ( P = 0.01 ) . At 1 year , there was significantly less thickening of the carotid wall ( P < 0.001 ) as well as persistent improvements in body fat content and lipid profiles in the group continuing an exercise program . Vascular function was significantly better in those children continuing exercise ( n=22 ) compared with children who withdrew from the exercise program ( n=19 ) ( P < 0.05 ) . Conclusions —Obesity-related vascular dysfunction in otherwise healthy young children is partially reversible with diet alone or particularly diet combined with exercise training at 6 weeks , with sustained improvements at 1 year in those persisting with diet plus regular exercise Background : The program The combined DAK therapy for obesity in children and adolescents ’ funded and conducted by the Deutsche Angestellten-Krankenkasse ( DAK ) , a German health insurance company , commenced in 2003 . The treatment program lasts for 1 year and comprises of 2 phases : an initial inpatient therapy for 6 weeks followed by a home-based outpatient treatment of the overweight children , adolescents , and their families for 10.5 months . The therapy complies with the guidelines of the German Working Group of Obesity in Childhood and Adolescence ( AGA ) . Participants and Methods : In this study , 162 obese children and adolescents were compared with a control group of 75 obese subjects recruited from the waiting list for the program . The aim was to analyze whether the changes in weight , eating behavior , and physical fitness during the therapy period are a result of the therapy itself or whether they are attributable to external effects . Body weight , height , and physical fitness were assessed through direct measurements while behavior and quality of life were assessed using self-report question naires . The development of body weight was evaluated using the BMI -SDS which is a measure of how many st and ard deviations an individual BMI is above or below the age- and gender-specific mean . Results : Within the observation period the BMI SDS decreased significantly by 0.36 ± 0.34 in the intervention group , whereas no changes of BMI -SDS were observed in the control group ( 0.04 ± 0.17 ) . The study revealed significant , positive treatment effects in exploratory analyses with regard to weight loss , behavior changes , physical fitness , and development of quality of life as a result of the therapy . These effects were not seen in the control group . Conclusion : We conclude that these positive developments are a result of the treatment program PURPOSE To determine the effect of increasing the aerobic component of the school 's physical activity program and improving the knowledge about weight control and blood pressure on the blood pressure and body fat of early adolescents . METHODS The subjects were 1140 youth aged 11 to 14 years ( 630 females , 510 males ; 64 % white , 24.4 % African-American , and 11.6 % " other " ) , who were r and omly assigned by school into four treatment groups : exercise only , education only , exercise and education combined , and control group . Heights , weights , and skinfold thicknesses were measured , and body mass index ( BMI ) was computed kg/m(2 ) . Blood pressure was obtained in duplicate using a r and om-zero mercury sphygmomanometer . Maximal oxygen uptake was predicted from a submaximal cycle ergometer test . Data were analyzed using analysis of covariance statistics , adjusting for gender , ethnicity , age , socioeconomic status , and initial baseline characteristics . RESULTS Systolic and diastolic blood pressures increased more in the control group than in the intervention groups ( p = .001 ) . The BMI did not change significantly ( p = .709 ) , but the sum of skinfolds increased less in subjects in the exercise intervention groups than the education only or control groups ( p = .0001 ) . The small increase in (p)VO(2)max of the combined exercise and education group was significantly greater than the education only group ( p = .0001 ) . CONCLUSION An exercise program for youth can have a positive effect on blood pressure independent of body weight loss Increasing fruits and vegetables ( FVs ) , a dietary recommendation for pediatric weight management , is theorized to reduce energy intake by reducing intake of more energy-dense foods , such as snack foods ( SFs ) . This study examined the relationship between changes in FV , SF , and energy intake in children enrolled in a 6-month , family-based behavioral pediatric weight management trial . Secondary data analyses examined dietary intake in 80 overweight ( ≥85th to < 95th percentile for body mass index [ BMI ] ) and obese ( ≥95th percentile for BMI ) children ( 7.2 ± 1.7 years ) with complete dietary records at 0 and 6 months . Participants were r and omized to one of three treatment conditions : ( 1 ) increased growth monitoring with feedback ; ( 2 ) decrease SFs and sugar sweetened beverages ; or ( 3 ) increase FVs and low-fat dairy . With treatment condition controlled in all analyses , FV intake significantly increased , while SF and energy intake decreased , but not significantly , from 0 to 6 months . Change in FV intake was not significantly associated with change in SF consumption . Additionally , change in FV intake was not significantly related to change in energy intake . However , reduction in SF intake was significantly related to reduction in energy intake . Changing only FVs , as compared to changing other dietary behaviors , during a pediatric obesity intervention may not assist with reducing energy intake Few studies have investigated the impact of school-based physical activity interventions on anthropometric characteristics concomitantly with aerobic and anaerobic capacities in young children . The present study aim ed to assess the effect of a 6-month physical activity program on body composition and physical fitness among primary schoolchildren . Four hundred fifty-seven children aged 6 to 10 years were r and omly assigned to the intervention group ( 229 children ) or observational group ( 228 children ) . Participants ’ height and weight were assessed , and obesity was determined using French reference curves for BMI . The sum of the four skinfolds and fat-free mass were determined . Ground tests were used to assess aerobic ( 20-m shuttle run test ) and anaerobic ( cycling peak power ) fitness before and after a 6-month physical activity intervention . The anthropometric modifications obtained over the 6 months can not be attributed to the intervention as the ANOVA revealed no group effect ( intervention vs. group ) . However , anaerobic and aerobic fitness were significantly improved , thanks to the program in both lean and obese children . A 6-month school-based physical activity intervention in 6- to 10-year-old children did not yield positive anthropometric improvements , but appears effective in terms of aerobic and anaerobic physical fitness . Two physical activity sessions per week in addition to st and ard physical education classes in primary schoolchildren bring effective results for the prevention of childhood obesity To assess the feasibility of conducting empirically supported family-based paediatric obesity group treatment via TeleMedicine . Seventeen families were r and omly assigned to one of two conditions ( physician visit , TeleMedicine ) . Measures included feasibility , satisfaction and intervention outcome measures such as BMI percentile , and nutrition and activity behaviours . Measures were completed at baseline , post-treatment and at 1-year follow-up . Analyses indicate that both feasibility and satisfaction data regarding the TeleMedicine intervention were positive . Intervention outcome indicates no change in BMI percentile or nutrition and activity behaviours for either treatment group . A behavioural family-based weight loss intervention delivered via TeleMedicine was well received by both parents and providers . Due to the small sample size , null findings regarding intervention outcome should be interpreted with caution . Future research should focus on methods to increase the impact of this intervention on key outcome variables BACKGROUND Cognitive behavioral therapy ( CBT ) teaches behavioral and cognitive strategies that focus on achieving and maintaining lifestyle changes . OBJECTIVE We examined the effectiveness of a CBT program ( CHOOSE HEALTH ) for improving body composition , diet , and physical activity in overweight and obese adolescents . DESIGN Adolescents [ 16 male , 31 female ; aged 14.5 + /- 1.6 y ; body mass index ( BMI ; in kg/m(2 ) ) 30.9 + /- 4.2 ] were block-matched into 2 groups by age , sex , Tanner stage , BMI , and hip and waist circumferences and were r and omly assigned to CBT or no treatment ( control ) . CBT consisted of 10 weekly sessions , followed by 5 fortnightly telephone sessions . RESULTS Compared with the control , over 20 wk , CBT improved ( significant group x time interactions ) BMI ( CBT , -1.3 + /- 0.4 ; control , 0.3 + /- 0.3 ; P = 0.007 ) , weight ( CBT , -1.9 + /- 1.0 kg ; control , 3.8 + /- 0.9 kg ; P = 0.001 ) , body fat ( CBT , -1.5 + /- 0.9 kg ; control , 2.3 + /- 1.0 kg ; P = 0.001 ) , and abdominal fat ( CBT , -124.0 + /- 46.9 g ; control , 50.1 + /- 53.5 g ; P = 0.008 ) . CBT showed a greater reduction in intake of sugared soft drinks as a percentage of total energy ( CBT , -4.0 + /- 0.9 % ; control , -0.3 + /- 0.9 % ; P = 0.005 for group x time interaction ) , which was related to reductions in weight ( r = 0.48 , P = 0.04 ) , BMI ( r = 0.53 , P = 0.02 ) , and waist circumference ( r = 0.54 , P = 0.02 ) . Physical activity did not change significantly . CONCLUSIONS A 10-wk CBT program followed by 10 wk of fortnightly phone contact improved body composition in overweight and obese adolescents . Changes in soft drink consumption may have contributed to this benefit BACKGROUND Childhood obesity is a major public health problem in the United States , particularly among American Indian communities . OBJECTIVE The objective was to evaluate the effectiveness of a school-based , multicomponent intervention for reducing percentage body fat in American Indian schoolchildren . DESIGN This study was a r and omized , controlled , school-based trial involving 1704 children in 41 schools and was conducted over 3 consecutive years , from 3rd to 5th grade s , in schools serving American Indian communities in Arizona , New Mexico , and South Dakota . The intervention had 4 components : 1 ) change in dietary intake , 2 ) increase in physical activity , 3 ) a classroom curriculum focused on healthy eating and lifestyle , and 4 ) a family-involvement program . The main outcome was percentage body fat ; other outcomes included dietary intake , physical activity , and knowledge , attitudes , and behaviors . RESULTS The intervention result ed in no significant reduction in percentage body fat . However , a significant reduction in the percentage of energy from fat was observed in the intervention schools . Total energy intake ( by 24-h dietary recall ) was significantly reduced in the intervention schools but energy intake ( by direct observation ) was not . Motion sensor data showed similar activity levels in both the intervention and control schools . Several components of knowledge , attitudes , and behaviors were also positively and significantly changed by the intervention . CONCLUSIONS These results document the feasibility of implementing a multicomponent program for obesity prevention in elementary schools serving American Indian communities . The program produced significant positive changes in fat intake and in food- and health-related knowledge and behaviors . More intense or longer interventions may be needed to significantly reduce adiposity in this population Background / Aims : There are limited data on regional variation of overweight and obesity in the Kingdom of Saudi Arabia . Therefore , the aim of this report is to explore the magnitude of these variation in order to focus preventive programs to regional needs . Setting and Design : Community-based multistage r and om sample of representative cohort from each region . Patients and Methods : the study sample was cross-sectional , representative of healthy children and adolescents from 2 to 17 years of age . Body mass index ( BMI ) was calculated according to the formula ( weight/height2 ) . The 2000 center for disease control reference was used for the calculation of prevalence of overweight and obesity defined as the proportion of children and adolescents whose BMI for age was above 85th and 95th percentiles respectively , for Northern , Southwestern and Central regions of the Kingdom . Chi-square test was used to assess the difference in prevalence between regions and a P value of < 0.05 was considered significant . Results : The sample size was 3525 , 3413 and 4174 from 2 - 17 years of age in the Central , Southwestern and Northern regions respectively . The overall prevalence of overweight was 21 % , 13.4 % and 20.1 % , that of obesity was 9.3 % , 6 % and 9.1 % in the Central , Southwestern and Northern regions respectively indicating a significantly-lower prevalence in the Southwestern compared to other regions ( P<0.0001 ) . Conclusions : This report revealed significant regional variations important to consider in planning preventive and therapeutic programs tailored to the needs of each region 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 OBJECTIVE To evaluate the effect of a high-protein diet on anthropometry , body composition , subjective appetite , and mood sensations in overweight and obese children attending a residential weight-loss camp . RESEARCH METHODS AND PROCEDURES Children ( 120 ; BMI , 33.1 + /- 5.5 kg/m(2 ) ; age , 14.2 + /- 1.9 years ) were r and omly assigned to either a st and ard or high-protein diet group ( 15 % vs. 22.5 % protein , respectively ) . All children were assessed at baseline and at the end of the camp for anthropometry , body composition , blood pressure , biochemical variables ( n = 27 ) , and subjective appetite and mood sensations ( n = 50 ) . RESULTS Attendance at the weight-loss camp result ed in significant improvements in most measures . Campers lost 5.5 + /- 2.9 kg in body weight ( p < 0.001 ) and 3.8 + /- 5.4 kg in fat mass ( p < 0.001 ) and reduced their BMI st and ard deviation score by 0.27 + /- 0.1 ( p < 0.001 ) and their waist circumference by 6.6 + /- 2.8 cm ( p < 0.001 ) . Subjective sensations of hunger increased significantly over the camp duration , but no other changes in appetite or mood were observed . There were no significant differences between the two diets on any physical or subjective measures . DISCUSSION Weight-loss camps are effective in assisting children to lose weight and improve on a range of health outcomes , independently of the protein content of the diet . The implication s of an increase in hunger associated with weight loss needs to be considered . Further work is warranted to investigate whether higher levels of dietary protein are feasible or effective in longer-term weight-loss interventions of this type This study aim ed to evaluate the weight loss and hunger motivation effects of an energy-restricted high-protein ( HP ) diet in overweight and obese children . In total , 95 overweight and obese children attended an 8-week ( maximum ) program of physical activity , reduced-energy intake , and behavior change education . Children were r and omly assigned to one of two isoenergetic diets ( st and ard ( SP ) : 15 % protein ; HP : 25 % protein ) , based on individually estimated energy requirements . Anthropometry and body composition were assessed at the start and end of the program and appetite and mood ratings completed on the first 3 consecutive weekdays of each week children attended camp . The HP diet had no greater effect on weight loss , body composition , or changes in appetite or mood when compared to the SP diet . Overall , campers lost 5.2 + /- 3.0 kg in body weight and reduced their BMI st and ard deviation score ( sds ) by 0.25 . Ratings of desire to eat increased significantly over the duration of the intervention , irrespective of diet . This is the third time we have reported an increase in hunger motivation in weight-loss campers and replicates our previous failure to block this with a higher protein diet . Further work is warranted into the management of hunger motivation as a result of negative energy balance OBJECTIVE To examine if reductions in added sugar intake or increases in fiber intake in response to a 16-week intervention were related to improvements in metabolic outcomes related to type 2 diabetes mellitus risk . DESIGN Secondary analysis of a r and omized control trial . SETTING Intervention classes at a lifestyle laboratory and metabolic measures at the General Clinical Research Center . PARTICIPANTS Fifty-four overweight Latino adolescents ( mean [ SD ] age , 15.5 [ 1 ] years ) . Intervention Sixteen-week study with 3 groups : control , nutrition , or nutrition plus strength training . MAIN OUTCOME MEASURES Body composition by dual-energy x-ray absorptiometry ; visceral adipose tissue by magnetic resonance imaging ; glucose and insulin incremental area under the curve by oral glucose tolerance test ; insulin sensitivity , acute insulin response , and disposition index by intravenous glucose tolerance test ; and dietary intake by 3-day records . RESULTS Fifty-five percent of all participants decreased added sugar intake ( mean decrease , 47 g/d ) and 59 % increased fiber intake ( mean increase , 5 g/d ) , and percentages were similar in all intervention groups , including controls . Those who decreased added sugar intake had an improvement in glucose incremental area under the curve ( -15 % vs + 3 % ; P = .049 ) and insulin incremental area under the curve ( -33 % vs -9 % ; P = .02 ) . Those who increased fiber intake had an improvement in body mass index ( -2 % vs + 2 % ; P = .01 ) and visceral adipose tissue ( -10 % vs no change ; P = .03 ) . CONCLUSIONS Individuals who reduced added sugar intake by the equivalent of 1 can of soda per day or increased fiber intake by the equivalent of a cup of beans showed improvements in key risk factors for type 2 diabetes , specifically in insulin secretion and visceral fat . Improvements occurred independent of group assignment and were equally likely to occur in control group participants OBJECTIVE We examined the effect of a 12-week family-based cognitive behavioural weight management programme developed for use in primary care setting s. METHODS The sample consisted of 49 children with obesity ( aged 7 - 13 years ; mean ± SD : 10.68 ± 1.24 ) . Families were r and omly assigned to immediate start-up of treatment or to a 12-week waiting list condition . Outcome measures were body mass index st and ard deviation score ( BMI SDS ) , self-esteem , symptoms of depression and blood parameters indicative of cardio-metabolic risk . Assessment s were conducted at baseline , post-treatment , post-waiting list and 12 months after treatment termination . RESULTS The mean reduction for the treatment group was -0.16 BMI SDS units compared with an increase of 0.04 units for the waiting list group ( p = .001 ) . For the entire sample , there was a significant post-treatment improvement on BMI SDS ( p = .001 ) , all self-esteem measures ( p = .001-.041 ) and symptoms of depression ( p = .004 ) . The mean BMI SDS reduction was -0.18 units post-treatment , and it was maintained at 12-month follow-up . Significant reductions were found in blood lipid levels of total cholesterol ( p = .03 ) , LDL-cholesterol ( p = .005 ) and HDL-cholesterol ( p = .01 ) at 12-month follow-up . The favourable effect on most of the psychological measures waned from post-treatment to follow-up , but not approaching baseline levels . Boys demonstrated significantly greater reductions in BMI SDS than girls ( p = .001 ) , while baseline psychiatric co-morbidity did not influence BMI SDS outcome . CONCLUSIONS The treatment shows significant and favourable effects on BMI SDS , self-esteem and symptoms of depression compared with a waiting list condition Background —The effects of diet and diet plus exercise training on muscle vasodilatation during physiological maneuvers in obese children are unknown . We tested the hypothesis that ( 1 ) blood pressure ( BP ) and forearm vascular conductance ( FVC ) responses during h and grip exercise and mental stress would be altered in obese children and ( 2 ) diet plus exercise training would restore BP and FVC responses during exercise and mental stress in obese children . Methods and Results —Thirty-nine obese children ( aged 10±0.2 years ) were r and omly divided into 2 groups : diet plus exercise training ( n=21 ; body mass index [ BMI ] = 28±0.5 kg/m2 ) and diet ( n=18 ; BMI = 30±0.4 kg/m2 ) . Ten age-matched lean control children ( BMI = 17±0.5 kg/m2 ) were also studied . Forearm blood flow was measured by venous occlusion plethysmography . BP was monitored noninvasively . H and grip exercise was performed at 30 % maximal voluntary contraction for 3 minutes . Stroop color word test was performed for 4 minutes . Baseline BP was significantly higher and FVC was significantly lower in obese children . During exercise and mental stress , BP responses were significantly higher and FVC responses were significantly lower in obese children . Diet and diet plus exercise training significantly reduced body weight . Diet and diet plus exercise training significantly decreased BP levels during exercise and mental stress . Diet plus exercise training , in contrast to diet alone , significantly increased FVC responses during exercise ( 3.7±0.3 versus 5.6±0.4 U ; P=0.01 ) and mental stress ( 3.5±0.5 versus 4.5±0.4 U ; P=0.02 ) . After diet plus exercise training , BP and FVC responses during exercise and mental stress were similar between obese children and the control group . Conclusions —Obesity exacerbates BP responses and impairs FVC responses during exercise and mental stress in children . Diet and exercise training restore BP and FVC responses in obese children To decrease BMI in overweight and obese children , improved dietary intake and increased physical activity are key elements . Our objective was to evaluate the impact of a 1-y food and physical activity intervention on energy and macronutrient intake in overweight and obese children . A r and omized open trial was conducted with 92 overweight or obese 10.4 ± 1.08-y-old children . The intervention included 14 group sessions with different themes regarding food and physical activity . Dietary intake was assessed with diet history interviews covering 14 d at baseline and 4-d food records after 1 y and was evaluated according to national dietary recommendations . The control group participated in the same measurements as the intervention group but did not take part in group sessions . After 1 y , both groups had decreased their energy intake ( EI ) relative to total energy expenditure , but the effect was more pronounced for the intervention group than for the control group . At 1 y follow-up , a larger proportion of children in the intervention group compared with the control group met the recommended intake of refined sugar ( P = 0.019 ) . However , the groups did not differ in the proportion children who met the recommended intake of dietary fiber . Further , SFA intake relative to total EI did not differ between the groups at 1 y follow-up . In conclusion , despite a rather comprehensive intervention , only modest effects were achieved with respect to reduced EI and improved macronutrient intake Increasing prevalence of childhood obesity calls for comprehensive and cost-effective educative measures in developing countries such as India . School-based educative programmes greatly influence children 's behaviour towards healthy living . We aim ed to evaluate the impact of a school-based health and nutritional education programme on knowledge and behaviour of urban Asian Indian school children . Benchmark assessment of parents and teachers was also done . We educated 40 196 children ( aged 8 - 18 years ) , 25 000 parents and 1500 teachers about health , nutrition , physical activity , non-communicable diseases and healthy cooking practice s in three cities of North India . A pre-tested question naire was used to assess r and omly selected 3128 children , 2241 parents and 841 teachers before intervention and 2329 children after intervention . Low baseline knowledge and behaviour scores were reported in 75 - 94 % government and 48 - 78 % private school children , across all age groups . A small proportion of government school children gave correct answers about protein ( 14 - 17 % ) , carbohydrates ( 25 - 27 % ) and saturated fats ( 18 - 32 % ) . Private school children , parents and teachers performed significantly better than government school subjects ( P < 0.05 ) . Following the intervention , scores improved in all children irrespective of the type of school ( P < 0.001 ) . A significantly higher improvement was observed in younger children ( aged 8 - 11 years ) as compared with those aged 12 - 18 years , in females compared with males and in government schools compared with private schools ( P < 0.05 for all ) . Major gaps exist in health and nutrition-related knowledge and behaviour of urban Asian Indian children , parents and teachers . This successful and comprehensive educative intervention could be incorporated in future school-based health and nutritional education programmes OBJECTIVE Maintaining weight loss results in childhood obesity treatment is difficult to achieve . Self-management techniques such as self-monitoring are associated with increased weight loss and maintenance . This study analyzes whether self-monitoring of lifestyle behaviours through a short message service maintenance treatment ( SMSMT ) via mobile phones with personalized feedback positively effects weight , lifestyle behaviours and psychological well-being in obese children . METHODS After 3 months of behavioural lifestyle treatment , 141 overweight and obese children ( 7 - 12 years ) were r and omly assigned to an intervention group receiving SMSMT for 9 months ( n = 73 ) or to the control group ( n = 68 ) . The intervention group sent weekly self-monitoring data on exercise and eating behaviour and their mood via mobile phones . In return , they received tailored feedback messages . Primary treatment outcomes were weight , eating behaviour and psychological well-being , i.e. competence , self-esteem and quality of life . Secondary outcome was adherence to the SMSMT . Data were analyzed with mixed modelling . RESULTS SMSMT did not improve treatment outcomes . Controls gained temporarily in physical health scores ( P = 0.01 ) . SMSMT completers sent on average every 2 weeks an SMS . Children who had greater weight loss during the first 3 months of lifestyle treatment sent more SMSs ( P = 0.04 ) . CONCLUSIONS We did not find a positive effect of SMSMT on weight , eating behaviour or psychological well-being in obese children . SMSMT seems to be a feasible method of treatment delivery . Future research should study variations of SMSMT to investigate how SMSMT can be more effective Use of meal replacements ( MRs ) in lifestyle modification programs ( LMPs ) for obese adults significantly increases weight loss , compared with prescription of an isocaloric conventional diet ( CD ) . This 12-month r and omized trial examined 113 obese adolescents ( mean ± s.d . age of 15.0 ± 1.3 years and BMI of 37.1 ± 5.1 kg/m2 ) who were assigned to a LMP , combined with meal plans of 1300 - 1500 kcal/day of CD ( self-selected foods ) or MR ( three SlimFast shakes , one prepackaged meal , five vegetable/fruit servings ) . After month 4 ( phase 1 ) , participants originally treated with MR were unmasked to their phase 2 ( months 5 - 12 ) r and om assignment : continued use of MR ( i.e. , MR+MR ) or transitioned to CD ( i.e. , MR+CD ) . Participants initially treated with CD in phase 1 , continued with CD ( i.e. , CD ) . All three groups were treated for an additional 8 months ( phase 2 ) . Regression models were used to evaluate percentage change in BMI from baseline to month 4 ( phase 1 ) , months 5 - 12 ( phase 2 ) , and baseline to month 12 . At month 4 , participants assigned to MR ( N = 65 ) achieved a mean ( ±s.e . ) 6.3 ± 0.6 % reduction in BMI , compared to a significantly ( P = 0.01 ) smaller 3.8 ± 0.8 % for CD participants ( N = 37 ) . In phase 2 , BMI increased significantly ( P < 0.001 ) in all three conditions , result ing in no significant ( P = 0.39 ) differences between groups in percentage change in BMI at month 12 . Across groups , mean reduction in BMI from baseline to month 12 was 3.4 ± 0.7 % ( P < 0.01 ) . Use of MR significantly improved short-term weight loss , compared with CD , but its continued use did not improve maintenance of lost weight BACKGROUND The rapid increase of obesity and diabetes risk beginning in youth , particularly those from disadvantaged communities , calls for prevention efforts . OBJECTIVE To examine the impact of a curriculum intervention , Choice , Control & Change , on the adoption of the energy balance-related behaviors of decreasing sweetened drinks , packaged snacks , fast food , and leisure screen time , and increasing water , fruits and vegetables , and physical activity , and on potential psychosocial mediators of the behaviors . DESIGN Ten middle schools were r and omly assigned within matched pairs to either intervention or comparison/delayed control conditions during the 2006 - 2007 school year . SUBJECTS/ SETTING Students were from low-income New York City neighborhoods ; 562 were in the intervention condition , and 574 in the comparison condition . INTERVENTION Students received the 24 Choice , Control & Change lessons that used science inquiry investigations to enhance motivation for action , and social cognitive and self-determination theories to increase personal agency and autonomous motivation to take action . MAIN OUTCOME MEASURES Self-report instruments to measure energy balance-related behaviors targeted by the curriculum and potential psychosocial mediators of the behaviors . STATISTICAL ANALYSES Analysis of covariance with group ( intervention/control ) as a fixed factor and pretest as covariate . RESULTS Students in intervention schools compared to the delayed intervention controls reported consumption of considerably fewer sweetened drinks and packaged snacks , smaller sizes of fast food , increased intentional walking for exercise , and decreased leisure screen time , but showed no increases in their intakes of water , fruits , and vegetables . They showed substantial increases in positive outcome expectations about the behaviors , self-efficacy , goal intentions , competence , and autonomy . CONCLUSIONS The Choice , Control & Change curriculum was effective in improving many of the specifically targeted behaviors related to reducing obesity risk , indicating that combining inquiry-based science education and behavioral theory is a promising approach Objective : The aim of the study was to compare the efficacy of group treatment stressing a health-promoting lifestyle with routine counseling in the treatment of childhood obesity . Design and subjects : Seventy obese children ( weight for height 115–182 % ) aged 7–9 years were r and omized either to routine counseling ( two appointments for children ) or to family-based group treatment ( 15 separate sessions for parents and children ) . These sessions included nutrition education , physical activity education and behavioral therapy . Outcome measures : Children 's weights and heights were measured at baseline , after the 6-month intervention and after the 6-month follow-up . The change of weight for height based on Finnish growth charts was used as the primary , and changes in body mass index ( BMI ) and BMI st and ard deviation scores ( BMI -SDS ) as secondary outcome measures . Results : Children attending the group treatment lost more weight for height ( 6.8 % ) than children receiving routine counseling ( 1.8 % ) ( P=0.001 ) . The difference was significant when the data were analyzed in four groups by the cut-off limits of 0 , −5 and −10 % for the change in weight for height . The respective decreases in BMI were 0.8 vs 0.0 ( P=0.003 ) and in BMI -SDS 0.3 vs 0.2 ( P=0.022 ) . The results remained similar in adjusted analyses . Both group and routine programs were feasible with a high , 87–99 % , participation rate in sessions and appointments and very low , 3 % or less , attrition rate from the programs . Six months after the intervention , beneficial effects were partly lost , but for changes in weight for height and BMI , the differences between the two treatment programs still were significant , and for BMI -SDS , there was a trend . Conclusions : Family-based group treatment that stresses a health-promoting lifestyle and is given separately for parents and children , offers an effective mode of therapy to treat obese school-aged children Background . Obesity has become the most common pediatric chronic disease in the modern era . Early prevention and treatment of childhood and adolescent obesity is m and ated . Surprisingly , however , only a minor fraction of obese children participate in weight reduction interventions , and the longer-term effects of these weight-reduction interventions among children have not been eluci date d. Objective . To examine prospect ively the short- and long-term effects of a 3-month , combined dietary-behavioral-physical activity intervention on anthropometric measures , body composition , dietary and leisure-time habits , fitness , and lipid profiles among obese children . Methods . In this r and omized prospect i ve study , 24 obese subjects completed the 3-month intervention and were compared with 22 obese , age- and gender-matched , control subjects . Results . At 3 months , there were significant differences in changes in body weight ( −2.8 ± 2.3 kg vs 1.2 ± 2.2 kg ) , BMI ( −1.7 ± 1.1 kg/m2 vs −0.2 ± 1.0 kg/m2 ) , body fat percentage ( from skinfold tests ; −3.3 ± 2.6 % vs 1.4 ± 4.7 % ) , serum total cholesterol level ( −24.6 ± 15.1 mg/dL vs 0.8 ± 18.7 mg/dL ) , low-density lipoprotein cholesterol level ( −23.3 ± 15.2 mg/dL vs −3.7 ± 17.3 mg/dL ) , and fitness ( 215 ± 107 seconds vs 50 ± 116 seconds ) in the intervention group versus the control group . After a 1-year follow-up period , there were significant differences between the intervention group ( n = 20 ) and the control group ( n = 20 ) in body weight ( 0.6 ± 6.0 kg vs 5.3 ± 2.7 kg ) , BMI ( −1.7 ± 2.3 kg/m2 vs 0.6 ± 0.9 kg/m2 ) , and body fat percentage . There was a significant increase in leisure-time physical activity among the intervention participants , compared with a decrease among the control subjects . Conclusions . Our data demonstrate the short- and longer-term beneficial effects of a combined dietary-behavioral-physical activity intervention among obese children . These results highlight the importance of multidisciplinary programs for the treatment of childhood obesity and emphasize their encouraging long-term effects BACKGROUND Childhood obesity is becoming a problem for Filipino children with an increasing national prevalence of pediatric overweight and obesity . A multidisciplinary approach combining behavioral therapy with diet and exercise is often advocated as having the greatest impact in pediatric weight management . OBJECTIVE To determine the effects of a weight loss program , which is a staged 3-mo , multidisciplinary intervention consisting of combined dietary , exercise , and behavioral methods in obese children . RESEARCH METHODS AND PROCEDURES Prospect i ve study done in a hospital-based weight management center ; duration of study : 15 mo ( November 2005 to January 2008 ) ; participants : 44 obese children ( aged 5 - 17 y ; body mass index [ BMI ] 85th-99th percentile ) ; outcome measures : change in weight , BMI , BMI z-score ( SD score ) ; secondary measures included changes in waist circumference , blood pressure , and body fat . Statistical tests : paired t tests , χ² test , Wilcoxon ranked sum test , regression analysis , and ANOVA . RESULTS At the end of the program , the patients demonstrated a decrease in weight , BMI , BMI z-score , body fat , systolic blood pressure , and waist circumference . Mean weight loss is 4.2 kg ( P < 0.01 ) with an average of 5.3 % weight loss ; BMI decreased by 1.5 units ( P < 0.01 ) , BMI z-score by 0.15 ( P < 0.004 ) , body fat by 14 % ( P < 0.01 ) , systolic blood pressure by 7.25 mm Hg ( P < 0.05 ) , and waist circumference by 5.4 cm ( P < 0.05 ) . Decrease in weight , BMI , and body fat were significantly correlated with number of sessions attended . CONCLUSION The use of a multidisciplinary 3-mo staged program result ed in an effective weight loss in obese Filipino children , which was directly related to the frequency of sessions attended PURPOSE Childhood obesity is a matter of great concern because of its negative health and social consequences . We examined the effect of a weight control program focusing on maternal education on childhood obesity , given that the incidence of obesity is greatly affected by parents . METHODS A two-group pre-test/post-test design was used . Participants consisted of 65 obese children and their mothers . The children were fourth- to sixth- grade elementary students who did not currently receive any therapy for weight loss . The children and their mothers were r and omly assigned to either an experimental ( n = 32 ) or a control group ( n = 33 ) . The 8-week intervention for mothers included one-time group education , three-time phone counseling , and four-time fliers regarding obesity management . Four outcomes ( self-control , obesity index , abdominal circumference , and body fat percentage ) were measured before and after the intervention . Chi-squared test or t test was used to test homogeneity between the two groups . Analysis of covariance was used to test the intervention effects . RESULTS After the intervention was completed , the level of self-control was significantly heightened and obesity levels in the other three outcomes were greatly lowered in the experimental group when compared with the control group . CONCLUSION Due to strong maternal effects on children 's weight control , mothers ' active participation must be encouraged in order to resolve childhood obesity The present study estimated the prevalence of childhood obesity and identified risk factors in 10 - 13 year old children . A cross-sectional study was conducted , including 200 children and their parents , in seven r and omly-selected primary schools across Patras , Greece . Height , weight , and waist circumference were measured , and self-reported information was collected via face-to-face interviews . Body mass index was calculated for the children and their parents . The effect of risk factors on overweight and obesity was analyzed using regression analysis . The prevalence of overweight and obesity was 32 % and 10.5 % , respectively . The odds of being overweight/obese increased in children whose parents had a lower educational level and /or higher body mass index . Fewer daily meals and more time spent in front of the television and /or on the computer were significantly associated with obesity in 10 - 13 year old children . The prevalence of excess weight in primary school children in Patras is of concern , especially for boys . Children 's nutritional habits , leisure activities , and parental characteristics influence their somatometric characteristics . These findings highlight the need for future weight loss interventions targeted at this population Milk consumption has decreased in children over the past years . This may play a role in the prevalence of pediatric obesity , because clinical studies have found a beneficial effect of milk consumption for weight management . The objectives of this study were to test whether high-milk consumption leads to greater weight loss and improvements in metabolic risk factors than low milk consumption during a 16-wk healthy eating diet . Overweight children aged 8 - 10 y were r and omized to either high ( 4 x 236 mL/d ) or low ( 1 x 236 mL/d ) milk consumption . Children were provided dietary counseling on healthy eating at baseline and at wk 1 , 2 , 4 , 6 , 8 , and 12 . Serum glucose , insulin , and lipids were measured in fasting children at baseline and wk 8 and 16 . An oral glucose tolerance test and body composition assessment by magnetic resonance imaging were conducted at baseline and endpoint . Body weight changes during the 16-wk study not differ between the high-milk ( 1.3 + /- 0.3 kg ) and low-milk ( 1.1 + /- 0.3 kg ) groups . There was no beverage x week interaction on any of the body composition and metabolic variables studied ( blood pressure , serum lipids , glucose , and insulin ) . There was a beverage x week interaction ( P = 0.044 ) on insulin area under the curve showing a trend toward reduced insulin output with a glucose challenge after high-milk consumption ( P = 0.062 ) . These data suggest that in overweight children , high-milk consumption in conjunction with a healthy diet does not lead to greater weight loss but may ameliorate insulin action compared with low-milk consumption BACKGROUND This study reports on effectiveness trial outcomes of Health in Motion , a computer tailored multiple behavior intervention for adolescents . METHODS Using school as level of assignment , students ( n=1800 ) from eight high schools in four states ( RI , TN , MA , and NY ) were stratified and r and omly assigned to no treatment or a multi-media intervention for physical activity , fruit and vegetable consumption , and limited TV viewing between 2006 and 2007 . RESULTS Intervention effects on continuous outcomes , on movement to action and maintenance stages , and on stability within action and maintenance stages were evaluated using r and om effects modeling . Effects were most pronounced for fruit and vegetable consumption and for total risks across all time points and for each behavior immediately post intervention . Co-variation of behavior change occurred within the treatment group , where individuals progressing to action or maintenance for one behavior were 1.4 - 4.2 times more likely to make similar progress on another behavior . CONCLUSION Health in Motion is an innovative , multiple behavior obesity prevention intervention relevant for all adolescents that relies solely on interactive technology to deliver tailored feedback . The outcomes of the effectiveness trial demonstrate both an ability to initiate behavior change across multiple energy balance behaviors simultaneously and feasibility for ease of dissemination Background : Treatment studies about childhood obesity in primary care are lacking . We hypothesized that providing a paid family membership to the YMCA would be effective in reducing weight . Methods : Patients 5 to17 years old in at least the 85th body mass index ( BMI ) percentile were eligible . All participants were scheduled to attend 4 nutrition classes and to return for evaluation at 2 , 4 , 6 , 9 , and 12 months . Participants were r and omized to nutrition classes only ( n = 39 ) or nutrition classes and family YMCA membership ( n = 44 ) . The primary outcome measure was year change in BMI -for-age percentile . Results : Median BMI percentile at baseline was 99 . Only 27 of 36 evaluable participants in the treatment group visited the YMCA . Four participants in the control group and one in the treatment group achieved the target reduction of 2 BMI percentile points ( Fisher 's exact , P = .17 ) . Within the treatment group , YMCA attendees had a mean increase of 0.30 BMI points compared with an increase of 0.60 BMI points in nonattendees ( P = .28 ) . Conclusion : In very obese children , eliminating financial barriers to YMCA membership is insufficient to induce more weight loss during 1 year compared with nutrition classes alone . Improvements in nutrition intake were reported by both groups BACKGROUND The objective of this study , focused on parents and children to reduce sedentary behavior , consumption of soft drinks and high-fat and salt containing snacks , and increase the consumption of fruits and vegetables , was to assess the effect of a six month intervention and an 18 month follow-up intervention on the body mass index , food consumption and physical activity of 2nd and 3rd grade elementary school children . METHODS This was a r and omized cluster controlled trial . School children were selected from 2nd and 3rd ( n = 532 ) grade . MEASUREMENTS BMI z-score for age and sex was calculated and classified according to the WHO ( 2006 ) . Abdominal obesity was defined as WC > 90th of NHANES III . RESULTS At six months of the study differences were observed in BMI , -0.82 ( p = 0.0001 ) . At 24 months , results such as an increase of z-score BMI and waist circumference , a decrease in abdominal obesity , eighth per cent remission and an incidence of 18 % of overweight and obesity were observed . Additionally , an increase ( p = 0.007 ) in vegetable intake and physical activity ( p = 0.0001 ) was also reported , along with a decrease in sedentary activities and the consumption of snacks high in fat and salt . CONCLUSIONS The results of this study indicate that with a comprehensive intervention there is a positive response to lifestyle changes and a reduction of abdominal obesity BACKGROUND The association of changes in oxidative and proinflammatory states with vascular function after diet and exercise intervention among obese children has not been previously explored . METHODS In this 6-week diet and exercise intervention study in 35 obese children , age 12 to 18 years , we evaluated the relationship between changes in anthropometric indices , measures of insulin resistance , C-reactive protein ( CRP ) , oxidized LDL ( ox-LDL ) , and oxidative stress markers with changes in carotid intima-media thickness ( C-IMT ) and flow mediated dilation ( FMD ) of the brachial artery . RESULTS At the end of the study , body mass index ( BMI ) , waist circumference , and percentage body fat were decreased ( P < 0.05 ) , but participants remained overweight ( BMI > or = 95th percentile ) . Although FMD improved ( P < 0.05 ) , the improvement in C-IMT did not reach statistical significance . The changes in BMI , waist circumference , fat mass , ox-LDL , malondialdehyde ( MDA ) , CRP , insulin , and homeostasis model assessment for insulin resistance ( HOMA-IR ) had an inverse correlation with the changes in mean FMD after adjustment for age and sex , with the highest correlations documented for ox-LDL , CRP , and WC . The age- and sex-adjusted changes in ox-LDL , waist circumference , CRP , MDA , and body fat mass had the highest correlations with changes in C-IMT . CONCLUSIONS Our findings suggest that a common inflammatory stress condition associated with childhood obesity , notably with abdominal fat deposition , may play a role in the development of the earliest stages of proatherosclerotic inflammatory processes and subsequent vascular dysfunction . These changes might be partially reversible by short-term diet and exercise intervention , even if patients do not reach ideal body weight Background The efficacy of pharmacological treatment in controlling childhood obesity is controversial . We aim ed to compare the effects of three types of drug regimens and placebo on generalized and abdominal obesity among obese children and adolescents who did not succeed to lose weight 3 months after lifestyle modification ( diet and exercise ) . Methods This triple-masked r and omized clinical trial was conducted among 180 participants aged 10–16 years . They were assigned r and omly to 4 groups of equal number to receive metformin , fluoxetine , a combination of the two drugs , or placebo . The trial lasted for 12 weeks and participants were followed up for an additional 12-week period . Results Overall , 91.1 % ( n=164 ) of the enrolled participants completed the trial . After the 12-week trial , the body mass index decreased significantly in all groups receiving medications [ approximately −1.2 ( 0.2 ) kg/m2 , P<0.05 ] . This decrease was not significant in the placebo group . Waist circumference decreased significantly in the groups receiving metformin [ −2.1 ( 0.4 ) cm , P=0.03 ) ] as well as in the group receiving a combination therapy of metformin and fluoxetine [ −2.5 ( 0.4 ) cm , P=0.01 ) ] . In the 24-week follow-up study , these anthropometric indexes were lower than the baseline in the group that had received a combination therapy of metformin and fluoxetine . No serious drug side-effects were reported . Conclusions A limited period of such treatment may help weight control , and might be used to encourage those children who have been refractory to weight loss for continuing the non-pharmacological programs . Our findings should be confirmed in future studies with a longer follow-up period Background Globally , efforts aim ed at the prevention of childhood obesity have led to the implementation of a range of school-based interventions . This study assessed whether augmenting physical activity ( PA ) within the school setting result ed in increased daily PA and decreased overweight/obesity levels in 6 - 9-year-old children . Methods Across the first to third primary school years , PA of 84 girls and 92 boys was objective ly monitored five times ( each for seven successive days ) using Yamax pedometer ( step counts ) and Caltrac accelerometer ( activity energy expenditure AEE - kcal/kg per day ) . Four schools were selected to participate in the research ( 2 intervention , 2 controls ) , comprising intervention ( 43 girls , 45 boys ) and control children ( 41 girls , 47 boys ) . The study was non-r and omized and the intervention schools were selected on the basis of existing PA-conducive environment . Analyses of variance ( ANOVA ) for repeated measures examined the PA programme and gender effects on the step counts and AEE . Logistic regression ( Enter method ) determined the obesity and overweight occurrence prospect over the course of implementation of the PA intervention . Results There was a significant increase of school-based PA during schooldays in intervention children ( from ≈ 1718 to ≈ 3247 steps per day ; and from 2.1 to ≈ 3.6 Kcal/Kg per day ) in comparison with the control children . Increased school-based PA of intervention children during schooldays contributed to them achieving > 10,500 steps and > 10.5 Kcal/Kg per school day across the 2 years of the study , and result ed in a stop of the decline in PA levels that is known to be associated with the increasing age of children . Increased school-based PA had also positive impact on leisure time PA of schooldays and on PA at weekends of intervention children . One year after the start of the PA intervention , the odds of being overweight or obese in the intervention children was almost three times lower than that of control children ( p < 0.005 ) , and these odds steadily decreased with the duration of the intervention . Conclusions The findings suggest that school-based PA ( Physical Education lessons , PA during short breaks and longer recesses , PA at after-school nursery ) in compatible active environments ( child-friendly gym and school playground , corridors with movement and playing around corners and for games ) has a vital role in obesity and overweight reduction among younger pupils Background There is an urgent need to develop and evaluate weight management interventions to address childhood obesity . Recent research suggests that interventions design ed for parents exclusively , which have been named parents as agents of change ( PAC ) approaches , have yielded positive outcomes for managing pediatric obesity . To date , no research has combined a PAC intervention approach with cognitive behavioural therapy ( CBT ) to examine whether these combined elements enhance intervention effectiveness . This paper describes the protocol our team is using to examine two PAC-based interventions for pediatric weight management . We hypothesize that children with obesity whose parents complete a CBT-based PAC intervention will achieve greater reductions in adiposity and improvements in cardiometabolic risk factors , lifestyle behaviours , and psychosocial outcomes than children whose parents complete a psycho-education-based PAC intervention ( PEP ) . Methods / Design This study is a pragmatic , two-armed , parallel , single-blinded , superiority , r and omized clinical trial . The primary objective is to examine the differential effects of a CBT-based PAC vs PEP-based PAC intervention on children ’s BMI z-score ( primary outcome ) . Secondary objectives are to assess intervention-mediated changes in cardiometabolic , lifestyle , and psychosocial variables in children and parents . Both interventions are similar in frequency of contact , session duration , group facilitation , lifestyle behaviour goals , and educational content . However , the interventions differ insofar as the CBT-based intervention incorporates theory-based concepts to help parents link their thoughts , feelings , and behaviours ; these cognitive activities are enabled by group leaders who possess formal training in CBT . Mothers and fathers of children ( 8–12 years of age ; BMI ≥85th percentile ) are eligible to participate if they are proficient in English ( written and spoken ) and agree for at least one parent to attend group-based sessions on a weekly basis . Anthropometry , cardiometabolic risk factors , lifestyle behaviours , and psychosocial health of children and parents are assessed at pre-intervention , post-intervention , 6- , and 12-months follow-up . Discussion This study is design ed to extend findings from earlier efficacy studies and provide data on the effect of a CBT-based PAC intervention for managing pediatric obesity in a real-world , outpatient clinical setting .Trial Registration Clinical Trials.gov identifier : BACKGROUND . The prevalence and seriousness of childhood obesity has prompted calls for broad public health solutions that reach beyond clinic setting s. Schools are ideal setting s for population -based interventions to address obesity . OBJECTIVE . The purpose of this work was to examine the effects of a multicomponent , School Nutrition Policy Initiative on the prevention of overweight ( 85.0th to 94.9th percentile ) and obesity ( > 95.0th percentile ) among children in grade s 4 through 6 over a 2-year period . METHODS . Participants were 1349 students in grade s 4 through 6 from 10 schools in a US city in the Mid-Atlantic region with ≥50 % of students eligible for free or reduced-price meals . Schools were matched on school size and type of food service and r and omly assigned to intervention or control . Students were assessed at baseline and again after 2 years . The School Nutrition Policy Initiative included the following components : school self- assessment , nutrition education , nutrition policy , social marketing , and parent outreach . RESULTS . The incidences of overweight and obesity after 2 years were primary outcomes . The prevalence and remission of overweight and obesity , BMI z score , total energy and fat intake , fruit and vegetable consumption , body dissatisfaction , and hours of activity and inactivity were secondary outcomes . The intervention result ed in a 50 % reduction in the incidence of overweight . Significantly fewer children in the intervention schools ( 7.5 % ) than in the control schools ( 14.9 % ) became overweight after 2 years . The prevalence of overweight was lower in the intervention schools . No differences were observed in the incidence or prevalence of obesity or in the remission of overweight or obesity at 2 years . CONCLUSION . A multicomponent school-based intervention can be effective in preventing the development of overweight among children in grade s 4 through 6 in urban public schools with a high proportion of children eligible for free and reduced-priced school meals Objective To assess the long term effects of an obesity prevention programme in schools . Design Longitudinal results after a cluster r and omised controlled trial . Setting Schools in southwest Engl and . Participants Of the original sample of 644 children aged 7 - 11 , 511 children were tracked and measurements were obtained from 434 children three years after baseline . Intervention The intervention was conducted over one school year , with four sessions of focused education promoting a healthy diet and discouraging the consumption of carbonated drinks . Main outcome measures Anthropometric measures of height , weight , and waist circumference . Body mass index ( BMI ) converted to z scores ( SD scores ) and to centile values with growth reference curves . Waist circumference was also converted to z scores ( SD scores ) . Results At three years after baseline the age and sex specific BMI z scores ( SD scores ) had increased in the control group by 0.10 ( SD 0.53 ) but decreased in the intervention group by −0.01 ( SD 0.58 ) , with a mean difference of 0.10 ( 95 % confidence interval −0.00 to 0.21 , P=0.06 ) . The prevalence of overweight increased in both the intervention and control group at three years and the significant difference between the groups seen at 12 months was no longer evident . The BMI increased in the control group by 2.14 ( SD 1.64 ) and the intervention group by 1.88 ( SD 1.71 ) , with mean difference of 0.26 ( −0.07 to 0.58 , P= 0.12 ) . The waist circumference increased in both groups after three years with a mean difference of 0.09 ( −0.06 to 0.26 , P=0.25 ) . Conclusions These longitudinal results show that after a simple year long intervention the difference in prevalence of overweight in children seen at 12 months was not sustained at three years Introduction This study assessed the short- and long-term effects of a 3-month family-based group treatment in the management of childhood obesity versus individual treatment . Material s and methods Eighty obese children , aged between 6 and 14 years , and their parents were included in this prospect i ve controlled clinical study . Forty participants were r and omly assigned for group treatment and the other 40 for individual treatment . A 3-month intervention program was focused on implementing healthy eating behaviors . The weight and height of the children were measured initially and at each treatment session and at follow-up visits . Body mass index was calculated and expressed as st and ard deviation score . Results and discussion At the end of 3-month treatment program , there was a significant decline in BMI SDS in both groups ( p < 0.001 ) . After 1 year of follow-up period , there was still a significant decrease in BMI SDS in the study group ( p < 0.001 ) , whereas the decrease in BMI SDS was not maintained over the follow-up period in the st and ard group . There was a significantly increased consumption of vegetable and fruit and reduced consumption of carbonated drinks and fruit juice in both groups ( p < 0.001 ) . Conclusion These findings demonstrate that the group treatment is more successful than the individual treatment in the management of childhood obesity PURPOSE To date , no study has examined the synergistic effects of a nutrition and combination of aerobic and strength training ( CAST ) on both adiposity and metabolic parameters in overweight Latina adolescent females . The goal was to assess if a 16-wk nutrition plus CAST pilot study had stronger effects on reducing adiposity and on improving glucose/insulin indices compared with control ( C ) , nutrition only ( N ) , and a nutrition plus strength training ( N + ST ) groups . METHODS In a 16-wk r and omized trial , 41 overweight Latina girls ( 15.2 + /- 1.1 yr ) were r and omly assigned to C ( n = 7 ) , N ( n = 10 ) , N + ST ( n = 9 ) , or N + CAST ( n = 15 ) . All intervention groups received modified carbohydrate nutrition classes ( once a week ) , whereas the N + ST also received strength training ( twice a week ) and the N + CAST received a combination of strength and aerobic training ( twice a week ) . The following were measured before and after intervention : strength by one repetition maximum , physical activity by the 7-d accelerometry and the 3-d physical activity recall , dietary intake by 3-d records , body composition by dual-energy x-ray absorptiometry ( DEXA ) , glucose/insulin indices by oral glucose tolerance test , and intravenous glucose tolerance test with minimal modeling . Across intervention group , effects were tested using ANCOVA with post hoc pairwise comparisons . RESULTS There were significant overall intervention effects for all adiposity measures ( weight , body mass index [ BMI ] , BMI z-scores , and DEXA total body fat ) , with a decrease of 3 % in the N + CAST group compared with a 3 % increase in the N + ST group ( P < or = 0.05 ) . There was also an intervention effect for fasting glucose with the N group increasing by 3 % and the N + CAST group decreasing by 4 % ( P < or = 0.05 ) . CONCLUSION The CAST was more effective than nutrition alone or nutrition plus strength training for reducing multiple adiposity outcomes and fasting glucose in overweight Latina girls . However , further research investigating and identifying intervention approaches that improve both adiposity and insulin indices , particularly in high-risk population s , are warranted Objective : To determine the long-term effect of a r and omized controlled trial of a dairy-rich diet on generalized and abdominal obesity , as well as on the components of the metabolic syndrome , among obese prepubescent children . Methods : This trial was conducted among a population -based sample of 120 obese prepubescent children who were r and omly assigned to 3 groups of equal number . In addition to attending 6 consecutive monthly family-centered education sessions about healthy lifestyle , an isocaloric dairy-rich diet ( > 800 mg ca/d ) was recommended to the children of one group ( DR : dairy-rich diet ) , the second group was placed on a caloric-restricted regimen ( ER : energy-restricted ) , and the third group received no additional recommendation ( C : controls ) . The groups were then followed-up twice a year for 3 years . Results : The mean age of the children was 5.6 ± 0.5 years . Of 120 participants , 95 ( 75 % ) completed the study ; the DR group had the highest retention rate . In all groups , body mass index-st and ard deviation score ( BMI -SDS ) and waist circumference decreased significantly after the 6-month trial , but had a sustained significant rise during the follow-up period to the end of the study ; however , in the DR group , this rise was significantly lower than in the 2 other groups . After the 6-month trial , in all groups , serum triglycerides ( TG ) and insulin levels decreased , and serum high-density lipoprotein cholesterol ( HDL-C ) level and homeostasis model assessment of insulin resistance ( HOMA-R ) increased . In the DR group , the TG , insulin and HOMA-R levels remained significantly lower than baseline until the 12-month follow-up . Conclusions : We suggest that in addition to lifestyle changes , an isocaloric diet rich in dairy products may be a well-accepted regimen and can be a safe and practical strategy for weight control in young , overweight children BACKGROUND Inadequate opportunities for physical activity at school and overall low levels of activity contribute to the high prevalence of overweight and obesity in American-Indian children . METHODS A school-based physical activity intervention was implemented which emphasized increasing the frequency and quality of physical education ( PE ) classes and activity breaks . Changes in physical activity were assessed using the TriTrac-R3D accelerometer in a sub sample of 580 of the students ( 34 % ) r and omly selected from the Pathways study cohort . Baseline measures were completed with children in second grade . Follow-up measurements were obtained in the spring of the fifth grade . RESULTS Intervention schools were more active ( + 6.3 to + 27.2 % ) than control schools at three of the four sites , although the overall difference between intervention and control schools ( approximately 10 % ) was not significant ( P>0.05 ) . Boys were more active than girls by 17 to 21 % ( P < or = .01 ) at both baseline and follow-up . CONCLUSIONS Despite the trend for greater physical activity at three of four study sites , and an overall difference of approximately 10 % between intervention and control schools , high variability in accelerometer AVM and the opportunity to measure physical activity on only 1 day result ed in a the failure to detect the difference as significant Purpose To evaluate the effect of multidisciplinary treatment on obesity and health-related quality of life ( HRQOL ) . Methods Obese children were r and omized to a multidisciplinary lifestyle treatment , including medical , nutritional , physical , and psychological counseling during 3 months , ( n = 40 , BMI -SDS ; 4.2 ± 0.7 , age ; 13.3 ± 2.0 ) or st and ard care , including an initial advice on nutrition and physical activity by the pediatrician ( n = 39 , BMI -SDS ; 4.3 ± 0.7 , age ; 13.1 ± 1.9 ) . At baseline , after 3 months of treatment and at 12 months follow-up , data were collected for BMI -SDS and a European vali date d question naire for assessing HRQOL ( DISABKIDS ) . Results A significantly reduced BMI -SDS was found for the intervention group after 3 months treatment ( 4.0 ± 0.9 vs. 4.2 ± 0.7 , P = 0.02 ) and at 12 months follow-up ( 3.8 ± 1.1 vs. 4.2 ± 0.7 , P = 0.03 ) . HRQOL in the intervention group was significantly improved at 12 months follow-up and unchanged in the obese control group . Agreement between child and parent report was moderate ( 67–85 % ) , with parents reporting a lower HRQOL for their obese children than children themselves in both groups . Conclusion Multidisciplinary treatment is effective in reducing BMI -SDS and improving HRQOL after 12 months follow-up BACKGROUND Physical Activity Across the Curriculum ( PAAC ) was a three-year cluster r and omized controlled trial to promote physical activity and diminish increases in overweight and obesity in elementary school children . METHODS Twenty-four elementary schools were cluster r and omized to the Physical Activity Across the Curriculum intervention or served as control . All children in grade s two and three were followed to grade s four and five . Physical Activity Across the Curriculum promoted 90 min/wk of moderate to vigorous intensity physically active academic lessons delivered by classroom teachers . Body Mass Index was the primary outcome , daily Physical activity and academic achievement were secondary outcomes . RESULTS The three-year change in Body Mass Index for Physical Activity Across the Curriculum was 2.0+/-1.9 and control 1.9+/-1.9 , respectively ( NS ) . However , change in Body Mass Index from baseline to 3 years was significantly influenced by exposure to Physical Activity Across the Curriculum . Schools with > or = 75 min of Physical Activity Across the Curriculum/wk showed significantly less increase in Body Mass Index at 3 years compared to schools that had < 75 min of Physical Activity Across the Curriculum ( 1.8+/-1.8 vs. 2.4+/-2.0 , p=0.02 ) . Physical Activity Across the Curriculum schools had significantly greater changes in daily Physical activity and academic achievement scores . CONCLUSIONS The Physical Activity Across the Curriculum approach may promote daily Physical activity and academic achievement in elementary school children . Additionally , 75 min of Physical Activity Across the Curriculum activities may attenuate increases in Body Mass Index OBJECTIVE This study sought to evaluate the effectiveness of a multidisciplinary elementary school-based intervention entitled Wellness , Academics & You . The primary areas of impact examined were BMI , consumption of fruits and vegetables , and physical activity . RESEARCH METHODS AND PROCEDURES The sample consisted of 1013 students in fourth and fifth grade s from 69 classes in four states . Intervention and comparison classes were r and omly selected at each school . Intervention teachers participated in workshops on the intervention and received program material s. BMI was calculated for baseline and post- data points based on measured height and weight collected by trained research teams . Baseline surveys were administered by the students ' teacher in the presence of one of the research team members and collected . RESULTS SPSS ( SPSS , Inc. , Chicago , IL ) analysis of post- data shows significant positive shifts ( p = 0.01 ) in BMI in the intervention group compared with the comparison group . Notable increases in the consumption of fruits and vegetables and increased physical activity levels were reported in the intervention group . DISCUSSION Data from this study indicate that this school-based program may contribute to the reduction of overweight and obesity . The intervention was well received by the classroom teachers and shows promise for a school-based obesity prevention initiative . This program has shown the capacity to effect positive changes in BMI through consumption of fruits and vegetables and physical activity . The evaluation covered a limited time period and , therefore , warrants additional studies to determine whether long-term program fidelity will result in continued improvement BACKGROUND & AIMS To assess the effects of a low cost behavioral prevention program in a preschool setting . METHODS 64 Kindergartens in 4 Bavarian regions were r and omly assigned as intervention or controls in a 2:1 ratio . Sample s of 1318 and 1340 children examined in the school entrance health examination at 5.7+/-2.6 and 17.6+/-2.3 months ( mean+/-st and ard deviation for first and second sample ) after the start of the program were analysed . MEASUREMENTS Main outcome measures were the prevalence of high fruit and vegetable consumption , low consumption of high caloric drinks assessed in parental question naires , overweight and obesity , and secondary , further dietary habits and results of motoric testing . RESULTS The program led to an increased proportion of children with high fruit and vegetable consumption already after 6 months , which was sustainable with adjusted odds ratios of 1.59 ( 1.26 : 2.01 ) and 1.48 ( 1.08 : 2.03 ) after 18 months . Subgroup analyses by gender , overweight and parental education , performed in order to assess consistency of effects , showed similar results . Prevalence of overweight and obesity as well as motoric testing results were not statistically different between intervention and control groups . CONCLUSION This low cost setting based behavioral intervention achieved sustainable effects on fruit and vegetable consumption in young children 18 months after the start of the intervention and showed effects also in the high risk groups of children from families with lower education levels , and children already overweight Background : Childhood obesity has become a nutritional problem in China since the 1990s . Aims : A family based behavioural treatment was developed and tested , to see if its use was feasible in China and to evaluate its impact on obese schoolchildren . Methods : In a single school in Beijing , 33 obese children were r and omly assigned to a treatment group and 35 to a control group . The treatment group participated in a family based behavioural treatment programme for two years . Height and weight were measured every six months for all participants . Blood pressure , cholesterol , and triglyceride levels were measured at baseline and after two years of programme implementation . Results : Body mass index ( BMI , kg/m2 ) was significantly reduced in the treatment group ( from 26.6 ( 1.7 ) to 24.0 ( 0.9 ) , 95 % CI 2.06 to 3.18 ) but not in the control group ( from 26.1 ( 1.5 ) to 26.0 ( 1.6 ) ) . Total cholesterol decreased 5.5 % and triglycerides 9.7 % in the treatment group . There was a significant correlation between change in BMI and change in triglycerides . There were no significant changes in plasma lipids in the controls . Blood pressure values also decreased significantly in the treatment , but not the control group . Conclusions : A family based behavioural intervention was feasible to use in treating obesity in schoolchildren in Beijing , China . After two years of implementation , it successfully decreased the degree of obesity , reduced levels of blood pressure , and decreased serum lipids in treatment ; there were no significant changes among control children OBJECTIVE Putative changes in the prevalence of obesity in Chinese children and adolescents in Shanghai , one of the most urbanized areas in China , were analyzed in a cross-sectional manner in 2003 - 2008 . METHODS One urban and one suburban district were r and omly selected . 70,582 students in 2003 and 86,355 students in 2008 from schools from within the two districts were examined . Anthropometric parameters were measured in all . Adiposity status was estimated using body mass index according to International Obesity Task Force st and ards . The prevalence of obesity was analyzed . RESULTS The st and ardized prevalence of overweight significantly increased from 12.75 to 14.2 % ( p < 0.01 ) , and the prevalence of obesity significantly increased from 3.35 to 3.94 % ( p < 0.01 ) during the study period . In contrast to data from developed countries , the prevalence of obesity decreased with age in both boys and girls . The prevalence of obesity and overweight in boys was significantly higher than that in girls ( p < 0.01 ) . Interestingly , the prevalence of overweight and obesity in the urban area was also significantly higher than that in suburb area ( p < 0.01 ) . CONCLUSION Over a 5-yr period , there was a significant increase in the prevalence of obesity in children and adolescents in Shanghai . The high percentage of overweight and obesity in the young age groups is of particular concern . Urbanization might be a causative factor for the increase in obesity prevalence in Chinese children in the Shanghai area Recent findings of a direct association of obesity and impaired health-related quality of life ( HRQOL ) in children suggest a need for early weight-management interventions that address psychosocial issues and lifestyle . Our aim was to compare the effects of exercise , diet , or diet + exercise on HRQOL in obese children . We hypothesized that HRQOL will improve as a result of the weight-loss intervention and will be correlated with the amount of weight loss achieved by each of the intervention groups . A total of 162 children aged 6 to 11 years with a body mass index ( BMI ) exceeding the 95th percentile were r and omly allocated to a 12-week regimens of diet , exercise , or diet + exercise . Weight , height , and percent fat mass were measured , and parents completed the Pediatric Quality of Life Inventory ( PedsQL ) 4.0 at baseline and at the end of the intervention . The reductions in BMI were significantly greater in the diet and diet + exercise groups than in the exercise group . Pediatric Quality of Life Inventory scores improved significantly , with no differences among the groups . A greater reduction in BMI occurred in children whose parents completed the PedsQL at baseline ( n = 105 ) than in children whose parents did not ( n = 15 ) ( -1.8 + /- 1.3 vs -1.0 + /- 1.5 ; P = .048 ) and in children whose parents completed the PedsQL at the end of the intervention ( n = 73 ) than in children whose parents did not ( n = 47 ) ( -2.0 + /- 1.3 vs -1.3 + /- 1.3 ; P = .013 ) . Weight-management programs that promote a healthy eating and physical activity can serve as an effective tool to improve the low HRQOL of obese children . Parental compliance is an important factor and may be assessed by the parents ' cooperativeness in completing question naires OBJECTIVE : To determine if beneficial effects of a weight-management program could be sustained for up to 24 months in a r and omized trial in an ethnically diverse obese population . PATIENTS AND METHODS : There were 209 obese children ( BMI > 95th percentile ) , ages 8 to 16 of mixed ethnic background s r and omly assigned to the intensive lifestyle intervention or clinic control group . The control group received counseling every 6 months , and the intervention group received a family-based program , which included exercise , nutrition , and behavior modification . Lifestyle intervention sessions occurred twice weekly for the first 6 months , then twice monthly for the second 6 months ; for the last 12 months there was no active intervention . There were 174 children who completed the 12 months of the r and omized trial . Follow-up data were available for 76 of these children at 24 months . There were no statistical differences in dropout rates among ethnic groups or in any other aspects . RESULTS : Treatment effect was sustained at 24 months in the intervention versus control group for BMI z score ( −0.16 [ 95 % confidence interval : −0.23 to −0.09 ] ) , BMI ( −2.8 kg/m2 [ 95 % confidence interval : −4.0–1.6 kg/m2 ] ) , percent body fat ( −4.2 % [ 95 % confidence interval : −6.4 % to −2.0 % ] ) , total body fat mass ( −5.8 kg [ 95 % confidence interval : −9.1 kg to −2.6 kg ] ) , total cholesterol ( −13.0 mg/dL [ 95 % confidence interval : −21.7 mg/dL to −4.2 mg/dL ] ) , low-density lipoprotein cholesterol ( −10.4 mg/dL [ 95 % confidence interval : −18.3 mg/dL to −2.4 mg/dL ] ) , and homeostasis model assessment of insulin resistance ( −2.05 [ 95 % confidence interval : −2.48 to −1.75 ] ) . CONCLUSIONS : This study , unprecedented because of the high degree of obesity and ethnically diverse background s of children , reveals that benefits of an intensive lifestyle program can be sustained 12 months after completing the active intervention phase Objective : The aim of this study was to evaluate the 8-year outcome of school-based intervention on weight status , lifestyle and blood pressure ( BP ) as part of the Kiel Obesity Prevention Study ( KOPS ) . Methods : Within a quasi-r and omized controlled trial , 240 intervention ( I ) and 952 non-intervention ( NI ) students at age 6 and 14 years were assessed in schools . Six nutrition units followed by 20-min running games were performed within the first year at school . Primary outcome was the 8-year change in body mass index st and ard deviation score ( BMI -SDS ) according to German references . Effective intervention was tested using multilevel linear regression analysis . Results : Eight-year changes in BMI SDS were + 0.18 and + 0.22 with increases in prevalence of overweight from 8.3 to 10.4 % and 7.0 to 11.2 % in I and NI students , respectively . Cumulative 8-year incidence of overweight was 5.9 % and 7.1 % in I and NI students , respectively . There was no overall effect of intervention , but a significant interaction was shown between the intervention and the socio-economic status ( SES ) , which demonstrated that in high SES , the 8-year change in BMI -SDS was in favour of I ( –0.17 in I and + 0.17 in NI ; p < 0.01 ) . Intervention had no measurable effects on lifestyle and BP . Conclusions : School-based health promotion has some favourable and sustained effects on 8-year changes in BMI -SDS , which are most pronounced in students of high SES families . The data argue in favour of further preventive measures PURPOSE The objective of this investigation was to examine the mechanisms of physical activity and dietary behavior change in the Program X intervention . METHODS Program X involved a clustered r and omized controlled design with six schools ( N=124 participants , mean age=14.1+/-0.8 years ) r and omized to intervention or control conditions for the 6-month study period . Physical activity and fruit and vegetable consumption were assessed using pedometers and question naires , respectively . The theoretical framework of the intervention was assessed using structural equation modeling , mediation , and moderation analyses . RESULTS The model explained 56 % of the variance in physical activity at 6-months , but did not represent a good fit to the data , chi(2)=87.43 , df=19 , p < .001 . The model explaining fruit and vegetable consumption explained 31 % of the variance and provided a good fit to the data , chi(2)=12.40 , df=10 , p=.259 . None of the variables satisfied the criteria for mediation or moderation in the physical activity model , but gender moderated the effects of intervention on fruit and vegetable consumption . CONCLUSIONS None of the hypothesized mediators were responsible for behavior change in the Program X intervention . Future studies should address the limitations of existing psychosocial scales and continue to explore the mechanisms of behavior change using model testing , mediation , and moderation analyses OBJECTIVES To assess the effect of a US obesity prevention intervention on dietary outcomes in English 9 - 10 year old children in 2006 . METHODS A pilot cluster r and omised controlled trial in 19 schools with children aged 9 to 10 with lessons taught by teachers . Diet was assessed at baseline and 5 months later using question naires . Full intention-to-treat analysis ( n=506 ) and analyses using only those with complete baseline and follow-up data ( n=393 ) . RESULTS 8.5 % of children ate 5 or more portions of fruit and vegetables per day . The odds of eating healthy amounts of fruit and vegetables ( OR 1.39 ( 95%CI : 0.69 , 2.80 ) ) and snacks ( OR 1.22 ( 95%CI : 0.68 , 2.21 ) ) were greater in children from the intervention compared to control schools . Point estimates were less than one for consumption of no portions of high fat food and one or zero high energy drinks . A full-scale trial would require 2640 children ( 106 schools ) with 80 % power to detect an odds ratio of at least 1.30 for healthy levels of consumption for the four dietary outcomes , with an alpha level of 0.01 . CONCLUSIONS The US intervention can be transferred to Engl and and it might be effective in increasing fruit and vegetable consumption and decreasing snacks OBJECTIVE The aim of this study was to conduct a preliminary evaluation of Children 's Appetite Awareness Training ( CAAT ) , a treatment for childhood obesity which encourages overweight children to eat in response to internal appetite cues . METHOD Overweight children ( ages 6 - 12 years old ) were r and omized to either the CAAT treatment group ( N = 23 ) , to receive 1-h treatment sessions over 6 weeks , or a wait-list group ( N = 24 ) . Weight and height of children and parents in both groups were assessed at pre- and post-treatment ( or equivalent time for wait-list control ) and at a 6-month follow-up for those in the CAAT group . RESULTS The intervention had a significant , short-term effect on the BMI of children who participated . Although at 6-month follow-up , children 's BMI has not increased significantly , the difference between pretreatment and follow-up BMI was no longer significant . DISCUSSION These results are encouraging for the use of CAAT with overweight children . Long-term effectiveness could be enhanced through increasing the duration of the program , adding booster sessions and increased involvement of parents OBJECTIVE To compare the effectiveness and safety of carbohydrate (CHO)-modified diets with a st and ard portion-controlled ( PC ) diet in obese children . STUDY DESIGN Obese children ( n=102 ) aged 7 - 12 years were r and omly assigned to a 3-month intervention of a low-CHO ( LC ) , reduced glycemic load ( RGL ) , or st and ard PC diet , along with weekly dietary counseling and biweekly group exercise . Anthropometry , dietary adherence , and clinical measures were evaluated at baseline and 3 , 6 , and 12 months . Analyses applied intention-to-treat longitudinal mixed models . RESULTS Eighty-five children ( 83 % ) completed the 12-month assessment . Daily caloric intake decreased from baseline to all time points for all diet groups ( P<.0001 ) , although LC diet adherence was persistently lower ( P<.0002 ) . At 3 months , body mass index z score was lower in all diet groups ( LC , -0.27 ± 0.04 ; RGL , -0.20 ± 0.04 ; PC , -0.21 ± 0.04 ; P<.0001 ) and was maintained at 6 months , with similar results for waist circumference and percent body fat . At 12 months , participants in all diet groups had lower body mass index z scores than at baseline ( LC , -0.21 ± 0.04 ; RGL , -0.28 ± 0.04 ; PC , -0.31 ± 0.04 ; P<.0001 ) , and lower percent body fat , but no reductions in waist circumference were maintained . All diets demonstrated some improved clinical measures . CONCLUSION Diets with modified CHO intake were as effective as a PC diet for weight management in obese children . However , the lower adherence to the LC diet suggests that this regimen is more difficult for children to follow , particularly in the long term The aim of this study was to evaluate the effectiveness of the Mind , Exercise , Nutrition , Do it ( MEND ) Program , a multicomponent community-based childhood obesity intervention ( www.mend central .org ) . One hundred and sixteen obese children ( BMI > or= 98 th percentile , UK 1990 reference data ) were r and omly assigned to intervention or waiting list control ( 6-month delayed intervention ) . Parents and children attended eighteen 2-h group educational and physical activity sessions held twice weekly in sports centers and schools , followed by a 12-week free family swimming pass . Waist circumference , BMI , body composition , physical activity level , sedentary activities , cardiovascular fitness , and self-esteem were assessed at baseline and at 6 months . Children were followed up 12 months from baseline ( 0 and 6 months postintervention for the control and intervention group , respectively ) . Participants in the intervention group had a reduced waist circumference z-score ( -0.37 ; P < 0.0001 ) and BMI z-score ( -0.24 ; P < 0.0001 ) at 6 months when compared to the controls . Significant between-group differences were also observed in cardiovascular fitness , physical activity , sedentary behaviors , and self-esteem . Mean attendance for the MEND Program was 86 % . At 12 months , children in the intervention group had reduced their waist and BMI z-scores by 0.47 ( P < 0.0001 ) and 0.23 ( P < 0.0001 ) , respectively , and benefits in cardiovascular fitness , physical activity levels , and self-esteem were sustained . High-attendance rates suggest that families found this intensive community-based intervention acceptable . Further larger controlled trials are currently underway to confirm the promising findings of this initial trial BACKGROUND Childhood obesity has become a health problem in urban areas in China . Intervention to reduce childhood obesity should be of high priority . School-based intervention programmes are needed to deal with the growing prevalence of childhood obesity in China . METHODS Five primary schools were selected r and omly for this study in the Beijing urban area in China ; two were allocated to the intervention group and three to the control group . A total of 2425 children ( 1029 children in intervention schools and 1396 children in control schools ) took part in the study for 3 years . In the intervention group , children and their parents were involved in a programme of nutrition education and physical activity . Control school students followed their usual health and physical education curriculum with no extra intervention . RESULTS After the 3-year intervention , the prevalence of overweight and obesity were significantly lower in the intervention schools than in the control schools ( overweight : 9.8 % vs. 14.4 % , P < 0.01 ; obesity : 7.9 % vs. 13.3 % , P < 0.01 ) . The prevalence of overweight and obesity decreased by 26.3 % and 32.5 % in intervention schools respectively after intervention . The prevalence of overweight and obesity increased in control schools . There was also significant difference in body mass index between intervention and control schools ( 18.2 + /- 2.6 vs. 20.3 + /- 3.4 , P < 0.01 ) after intervention . More non-obese children became obese in the control schools ( 7.0 % ) than in the intervention schools ( 2.4 % ) at end line ( P < 0.01 ) . Among the children who were obese at baseline , 49.2 % remained obese at end line in intervention schools while 61.9 % remained obese in control schools ( P < 0.01 ) . CONCLUSIONS Our study showed that an intervention programme could be feasible in schools in Beijing , China . The prevalence of overweight and obesity was reduced in schoolchildren in Beijing through an intervention focused on nutrition education and physical activity . Overweight and obesity children as well as normal weight children and their parents should be involved in such an intervention programme OBJECTIVE The aim of this study was to compare the effect of a hospital clinic group- versus home-based combined exercise-diet program for the treatment of childhood obesity . METHODS One hundred ten overweight/obese Spanish children and adolescents ( 6 - 16 years ) in 2 intervention groups ( hospital clinic group-based [ n = 45 ] and home-based [ n = 41 ] ) and a sex-age-matched control group ( n = 24 ) were r and omly assigned to participate in a 6-month combined exercise ( aerobic and resistance training ) and Mediterranean diet program . Anthropometric values ( including body weight , height , body mass index , BMI -Z score , and waist circumference ) were measured pre- and postintervention for all the participants . Percentage body fat was also determined with a body fat analyzer ( TANITA TBF-410 M ) . RESULTS Our study showed a significant reduction in percentage body fat and body mass index Z-score among both intervention-group participants ( 4 % , 0.16 , hospital clinic group-based ; 4.4 % , 0.23 , home-based ; P < .0001 ) . There was also a significant reduction in waist circumference in the home-based group ( 4.4 cm ; P = .019 ) . Attendance rates at intervention sessions were equivalent for both intervention groups ( P = .805 ) . CONCLUSIONS The study findings indicate that a simple home-based combined exercise and Mediterranean diet program may be effective among overweight and obese children and adolescents , because it improves body composition , is feasible and can be adopted on a large scale without substantial expenses OBJECTIVE : To investigate the effect of protein and glycemic index ( GI ) on body composition among European children in the r and omized , 6-month dietary intervention DiOGenes ( diet , obesity , and genes ) family-based study . PATIENTS AND METHODS : In the study , 827 children ( 381 boys and 446 girls ) , aged 5 to 18 years , completed baseline examinations . Families with parents who lost ≥8 % of their weight during an 8-week run-in low-calorie diet period were r and omly assigned to 1 of 5 ad libitum diets : low protein (LP)/low glycemic index ( LGI ) ; LP/high GI ( HGI ) ; high protein (HP)/LGI ; HP/HGI ; and control diet . The target difference was 15 GI U between the LGI/HGI groups and 13 protein percentage points between the LP/HP groups . There were 658 children examined after 4 weeks . Advice on food-choice modification was provided at 6 visits during this period . No advice on weight loss was provided because the focus of the study was the ability of the diets to affect outcomes through appetite regulation . Anthropometric measurements and body composition were assessed at baseline , week 4 , and week 26 . RESULTS : In the study , 465 children ( 58.1 % ) completed all assessment s. The achieved differences between the GI and protein groups were 2.3 GI U and 4.9 protein percentage points , respectively . The LP/HGI group increased body fat percentage significantly more than the other groups ( P = .040 ; partial η2 = 0.039 ) , and the percentage of overweight/obese children in the HP/LGI group decreased significantly during the intervention ( P = .031 ) . CONCLUSIONS : Neither GI nor protein had an isolated effect on body composition . However , the LP/HGI combination increased body fat , whereas the HP/LGI combination was protective against obesity in this sample of children OBJECTIVE The authors performed a group-based program for obese children and adolescents in Bavaria , Germany to enable them to establish a health-oriented lifestyle and to reduce overweight . The authors compared this program with a control approach based on the patients ' own initiative . DESIGN This is a controlled clinical trial . SETTING A nutrition program for out patients in a German university hospital . PARTICIPANTS Seventy-three obese patients aged 7 to 15 years ( mean 11.2 years ) were recruited by pediatricians and local newspaper reports and r and omized into intervention and control groups . Children and adolescents in each group were divided into 3 groups according to age--7 - 8 years , 9 - 10 years , and 11 - 13 years . Children were classified overweight ( defined as body mass index ( BMI ) > 90th percentile for age and gender ) , obese ( BMI > 97th percentile ) , and extremely obese ( BMI > 99.5th percentile ) , according to the European Childhood Obesity Group and the German Working Group on Pediatric Obesity , congruent with adult st and ards used to assess overweight and obesity . INTERVENTION Thirty-seven patients ( age 7 - 13 years , mean 10.9 years ) for the 1-year intervention . This intervention consisted of modules for physical activity , nutritional education , and coping strategies . The program was performed twice each week and incorporated parental participation and medical supervision , including laboratory tests . The obese controls ( n = 36 , age 8 - 15 years , mean 11.6 years ) received written therapeutic advice during a visit at 0 and 6 months in the outpatient clinic . MAIN OUTCOME MEASURE The primary outcome variable was the body mass index ( BMI ) z score . ANALYSIS Analysis of variance and t test were used , and a P value < .05 was considered significant . RESULTS There was a reduction of BMI z score in the active treatment group ( P < .05 ) , but not for controls . Moreover , the active group showed beneficial effects for body mass index ( BMI ) , fat mass , and systolic blood pressure 12 months after beginning the intervention . CONCLUSIONS AND IMPLICATION S Group-based programs for young , obese patients can be effective tools for establishing a health-oriented lifestyle and reducing the burden of obesity BACKGROUND . Parenting-skills training may be an effective age-appropriate child behavior-modification strategy to assist parents in addressing childhood overweight . OBJECTIVE . Our goal was to evaluate the relative effectiveness of parenting-skills training as a key strategy for the treatment of overweight children . DESIGN . The design consisted of an assessor-blinded , r and omized , controlled trial involving 111 ( 64 % female ) overweight , prepubertal children 6 to 9 years of age r and omly assigned to parenting-skills training plus intensive lifestyle education , parenting-skills training alone , or a 12-month wait-listed control . Height , BMI , and waist-circumference z score and metabolic profile were assessed at baseline , 6 months , and 12 months ( intention to treat ) . RESULTS . After 12 months , the BMI z score was reduced by ∼10 % with parenting-skills training plus intensive lifestyle education versus ∼5 % with parenting-skills training alone or wait-listing for intervention . Waist-circumference z score fell over 12 months in both intervention groups but not in the control group . There was a significant gender effect , with greater reduction in BMI and waist-circumference z scores in boys compared with girls . CONCLUSION . Parenting-skills training combined with promoting a healthy family lifestyle may be an effective approach to weight management in prepubertal children , particularly boys . Future studies should be powered to allow gender sub analysis The prevalence of childhood overweight has increased significantly , with the highest rates noted among Mexican Americans . Many negative health outcomes are associated with overweight ; thus , there is a need for effective weight-loss interventions tailored to this group . This study evaluated 24-month outcomes of a r and omized , controlled trial involving an intensive lifestyle-based weight maintenance program targeting overweight Mexican-American children at a charter school in Houston , Texas . A total of 60 children ( 33 males , 55 % ) between the ages of 10 and 14 at or > 85th percentile for BMI were recruited . Participants were r and omized to an instructor-led intervention ( ILI ) or a self-help ( SH ) program , both aim ed at modifying eating and physical activity behaviors using behavior modification strategies . Changes in participants ' st and ardized BMI ( z BMI ) were assessed at baseline , 1 , and 2 years . Tricep skinfold , total cholesterol , triglycerides , high-density lipoprotein cholesterol , and calculated low-density lipoprotein were assessed at baseline and 1 year . ILI participants showed significantly greater decreases in z BMI at 1 and 2 years ( F = 26.8 , P < 0.001 , F = 4.1 , P < 0.05 , respectively ) compared to SH controls . ILI participants showed greater improvements in body composition , as measured by tricep skinfold ( F = 9.75 , P < 0.01 ) . Children in the ILI condition experienced benefits with respect to total cholesterol ( F = 7.19 , P < 0.05 ) and triglycerides ( F = 4.35 , P < 0.05 ) compared to children in the SH condition . Overall , the school-based intervention result ed in improved weight and clinical outcomes in overweight Mexican-American children , and z BMI was maintained over 2 years Although r and omized controlled trials demonstrated the long-term efficacy of lifestyle interventions in overweight children , the effects of these interventions in clinical practice under real-life conditions are largely unknown . One hundred twenty-nine centers specialized in outpatient pediatric obesity care participated in this quality assessment . All patients presenting before the year 2006 for lifestyle intervention of at least 6 months duration in these institutions were analyzed in a 2-year follow-up . A total of 21,784 ( 45 % male ) overweight children and adolescents aged 2 - 20 years ( mean BMI 30.4 kg/m2 , mean SDS- BMI 2.51 , mean age 12.6 years ) were included in the analysis . Based on an intention-to-treat analysis with variables set back to baseline in lost of follow-up , 22 % of the children reduced their SDS- BMI after 6 months , 15 % after 12 months , and 7 % after 24 months , but only in 24 , 17 , and 8 % of children , respectively , complete data were available . In the five treatment centers with the best outcome ( 518 patients ) , 83 % of the children reduced their overweight after 6 months , 67 % after 12 months , and 51 % after 24 months . Under real-life conditions , most treatment centers can not prove the long-term efficacy of their interventions due to high drop-out rate or lack of documentation . Conversely , some institutions achieved a reduction of overweight in nearly the half of their patients 24 months after baseline demonstrating the great heterogeneity in outcome . To improve the effectiveness of lifestyle interventions in real-life study ing , the process and structure quality as well as their long-term results is urgently needed 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 BACKGROUND This study tests the feasibility of an innovative school-based program for obesity prevention among adolescent girls . New Moves was implemented as a multicomponent , girls-only , high-school physical education class . METHODS Six schools were equally r and omized into intervention and control conditions . Data were collected at baseline , postintervention , and 8-month follow-up to assess program impact on physical activity , eating patterns , self-perceptions , and body mass index ( BMI ) among 89 girls in the intervention and 112 girls in the control conditions . Program evaluation also included interviews with school staff , parent surveys , and participant interviews and process evaluation surveys . RESULTS The feasibility of implementing New Moves was high , as indicated by strong satisfaction among participants , parents , and school staff , and by program sustainability . Participants perceived a positive program impact on their physical activity , eating patterns , and self-image . Girls in the intervention significantly progressed in their stage of behavioral change for physical activity from baseline to follow-up . However , for the majority of outcome variables , differences between intervention and control schools at postintervention and follow-up were not statistically significant . CONCLUSIONS New Moves was well received and fills a needed niche within school physical education programs . An exp and ed intervention and evaluation is needed to enhance and assess long-term program effectiveness OBJECTIVE To evaluate the 4-year outcome of a school-based health promotion on weight status as part of the Kiel Obesity Prevention Study ( KOPS ) . RESEARCH METHODS AND PROCEDURES Within a cluster- sample d quasi-r and omized controlled trial , 1764 children at 6 and 10 years of age were assessed between 1996 and 2005 in 32 primary schools in Kiel , North Germany . Six nutrition units followed by 20-minute running games were performed within the first year at school . Prevalence , incidence , and remission of overweight were main outcome measures . RESULTS The 4-year change in BMI was + 11.6 % , with increases in prevalence of overweight and obesity from 5.2 % to 11.1 % and 3.9 % to 5.1 % , respectively . Cumulative 4-year incidence of overweight and obesity was 9.2 % and 3.1 % , respectively . Intervention had no effect on mean BMI . The effect on prevalence was significant in children from families with high socioeconomic status [ odds ratio ( OR ) , 0.35 ; 95 % confidence interval ( CI ) , 0.14 to 0.91 ] and marginally significant in children of normal-weight mothers ( OR , 0.57 ; 95 % CI , 0.33 to 1.00 ) . Cumulative 4-year incidence of overweight was lower only in intervention children from families with high socioeconomic status ( OR , 0.26 ; 95 % CI , 0.07 to 0.87 ) . Remission of overweight was most pronounced in children of normal-weight mothers ( OR , 5.43 ; 95 % CI , 1.28 to 23.01 ) . Prevalence of underweight was unchanged . The intervention had minor but favorable effects on lifestyle . DISCUSSION A school-based health promotion has sustainable effects on remission and incidence of overweight ; it was most pronounced in children of normal-weight mothers and children from families with high socioeconomic status . There was no effect on obesity . The data argue in favor of additional measures of prevention OBJECTIVE NOURISH is a community-based treatment program for parents of overweight and obese children ( ages 6 - 11 , BMI ≥ 85 th percentile ) . This study examined the impact of Nourishing Our Underst and ing of Role modeling to Improve Support and Health on child and parent dietary intake , secondary trial outcomes . METHODS In Virginia from 2008 to 2009 , this r and omized controlled pilot was implemented and dietary assessment of parents and children conducted at baseline , post-test , and 6-month follow-up . Parents ( 85 % female , 62 % African American , mean BMI = 34.1 ± 9.1 ) were r and omized into intervention ( n=46 ) or control ( n=50 ) groups . Children 's ( mean age=8.6 ± 1.5 ) mean Body Mass Index percentile was 98.1 ± 2.6 . Parents completed 24-hour dietary records for themselves and their child(ren ) . Repeated measures analyses assessed treatment effects over time . T-tests evaluated within-group changes from baseline to post-test and to follow-up , using a modified intent-to-treat approach . RESULTS Both groups reported significant dietary changes , with few treatment effects found . For parents in NOURISH , significant improvements were found in intakes of total kilocalories/day , grams/day of carbohydrates and sugar , and percent calories from protein ( p<0.05 ) . Among control group children , significant improvements in total kilocalories/day and grams/day of carbohydrates and sugar were found ( p<0.05 ) . CONCLUSIONS Among parents who self-select into a childhood obesity program , minimal intervention can elicit short-term dietary changes comparable to those of a structured intervention OBJECTIVE To evaluate the efficacy and safety of a carbohydrate restricted versus a low fat diet on weight loss , metabolic markers , body composition , and cardiac function tests in severely obese adolescents . STUDY DESIGN Subjects were r and omly assigned to 1 of 2 diets : a high protein , low carbohydrate ( 20 g/d ) diet ( high protein , low carbohydrate , HPLC ) or low fat ( 30 % of calories ) regimen for 13 weeks ; close monitoring was maintained to evaluate safety . After the intervention , no clinical contact was made until follow-up measurements were obtained at 24 and 36 weeks from baseline . The primary outcome was change in body mass index Z-score for age and sex ( BMI -Z ) at 13 , 24 , and 36 weeks . RESULTS Forty-six subjects ( 24 HPLC , 22 in low fat ) initiated and 33 subjects completed the intervention ; follow-up data were available on approximately half of the subjects . Significant reduction in ( BMI -Z ) was achieved in both groups during intervention and was significantly greater for the HPLC group ( P = .03 ) . Both groups maintained significant BMI -Z reduction at follow-up ; changes were not significantly different between groups . Loss of lean body mass was not spared in the HPLC group . No serious adverse effects were observed related to metabolic profiles , cardiac function , or subjective complaints . CONCLUSIONS The HPLC diet is a safe and effective option for medically supervised weight loss in severely obese adolescents PURPOSE Evaluate the effect of the Kids Living Fit hospital-based intervention on body mass index ( BMI ) percentile , adjusted for age ( months ) and gender in children ages 8 - 12 years with BMI percentiles > or = 85 . DESIGN AND METHODS Twelve weekly exercise sessions and three nutrition presentations were held . Nurses recorded BMI and waist circumference at baseline , week 12 , and week 24 . Participants completed food and activity diaries . RESULTS Of the 32 participants enrolled , 16 completed all outcome measures and experienced a decrease in average BMI , BMI percentile , and waist circumference between baseline and weeks 12 and 24 . PRACTICE IMPLICATION S Hospitals can offer exercise and nutrition programs to decrease childhood obesity in their communities BACKGROUND & AIMS R and omized controlled trials ( RCT ) have demonstrated the effectiveness of lifestyle interventions in obese children . However , the effectiveness of interventions for overweight , but no obese children has not been demonstrated yet by RCTs . METHODS A total of 66 overweight ( BMI > 90th < or = 97th percentile ) children ( mean age 11.5+/-1.6 years , 58 % females , mean BMI 23.4+/-1.5kg/m(2 ) ) were r and omized into a control group ( CG ) ( n=32 ; no intervention for a duration of 6 months ) or intervention group ( IG ) ( n=34 ; 6 months intervention " Obeldicks light " based on physical activity , nutrition education , and behaviour counselling ) . BMI , waist circumference , skinfold thickness , bioimpedance analyses , blood pressure , physical activity based on question naires , and three-day-weighed dietary records were determined at baseline ( T0 ) and 6 months ( T1 ) later . Degree of overweight was calculated as BMI -SDS . Comparisons were performed on an intention-to-treat approach . RESULTS The drop-out rate was 3 % in IG and 16 % in CG . At T1 , 94 % of the children in IG decreased their BMI -SDS and 24 % of them were normal weight . The changes between T0 and T1 in BMI -SDS differed significantly ( p<0.001 ) between IG and CG ( CG : + 0.05+/-0.19 BMI -SDS ; IG : -0.26+/-0.22 BMI -SDS ) . Similar findings were observed for blood pressure , waist circumference , skinfold thickness , and fat mass based on bioimpedance analyses . In the IG , energy , fat and sugar intake decreased significantly between T0 and T1 , while no significant changes were observed in the CG . CONCLUSIONS The lifestyle intervention was associated with an improvement of dietary patterns and was effective in reducing degree of overweight , fat mass , waist circumference , and blood pressure We evaluated the efficacy of a 6-month clinic and home-based behavioral intervention ( Learning about Activity and Underst and ing Nutrition for Child Health ; LAUNCH ) to reduce obesity in preschool children ≥95th BMI percentile compared to enhanced st and ard of care ( Pediatrician Counseling ; PC ) . LAUNCH was a family-based behavioral intervention that taught parents to use child behavior management strategies to increase healthy eating and activity for their children and themselves . PC presented the same diet and activity recommendations , but was delivered in a one-time PC session . Eighteen children aged 2 - 5 years ( mean 4.71 ± 1.01 ) with an average BMI percentile of 98 ( ±1.60 ) and an overweight parent were r and omized to LAUNCH or PC . Assessment s were conducted at baseline , 6 months ( end of LAUNCH treatment ) and 12 months ( 6 months following LAUNCH treatment ) . LAUNCH showed a significantly greater decrease on the primary outcomes of child at month 6 ( post-treatment ) BMI z ( -0.59 ± 0.17 ) , BMI percentile ( -2.4 ± 1.0 ) , and weight gain ( -2.7 kg ± 1.2 ) than PC and this difference was maintained at follow-up ( month 12 ) . LAUNCH parents also had a significantly greater weight loss ( -5.5 kg ± 0.9 ) at month 6 and 12 ( -8.0 kg ± 3.5 ) than PC parents . Based on the data from this small sample , an intensive intervention that includes child behavior management strategies to improve healthy eating and activity appears more promising in reducing preschool obesity than a low intensity intervention that is typical of treatment that could be delivered in primary care |
12,960 | 27,843,376 | Patients with OA diagnosed with these comorbidities experienced more pain , had frequent hospital visits , took more medication , and reported less optimal outcomes .
Anxiety and depression adversely impact the QoL of patients with OA . | BACKGROUND Anxiety and depression are common psychological comorbidities that impact the quality of life ( QoL ) of patients .
In this systematic review , we 1 ) determined the impact of anxiety and depression on outcomes in patients with osteoarthritis ( OA ) and 2 ) summarized unique challenges these comorbidities present to current OA management . | OBJECTIVE To study the natural history of peripheral joint osteoarthritis ( OA ) and assess its impact over eight years in a prospect i ve study of 500 patients . METHODS 500 consecutive patients with peripheral joint OA were recruited from a hospital-based rheumatology clinic . All were invited for review 3 and 8 years after entry . Joint sites involved , pain severity , change in index joints , global change in the condition , use of medication , surgery and walking aids were all recorded at each visit , and after eight years disability was assessed by the health assessment question naire ( HAQ ) and anxiety and depression by the Hospital anxiety and depression scale ( HAD ) . RESULTS At eight-year review , 349 patients were seen : 90 % of those remaining alive . Outcome was heterogeneous . Sixty patients ( 17.2 % ) reported worsening in all three subjective parameters ( pain , index joint and global change ) compared with 22 ( 6.3 % ) who improved in all three parameters . Using this definition of worsening or improvement , strong baseline predictors of clinical outcome did not emerge . For further description , the group was split according to the index joint sites involved at entry to the study , there being 111 with knee OA alone , 87 with h and and knee OA , 72 with h and disease alone , and 29 with hip disease alone . Forty-four percent of those with lone h and disease at entry had acquired significant knee or hip OA 8 years later . The mean HAQ and HAD scores at 8 years were high , especially in those with knee disease , indicating significant disability as a result of the disease . Those with knee or knee and h and disease had the worst outcome in all parameters recorded . The data showed a general decrease in use of NSAIDs over the eight years , but an increase in utilization of analgesics , surgery ( especially for hip disease ) and walking aids . CONCLUSIONS Patients with peripheral joint OA of sufficient severity to lead to hospital referral have a heterogeneous , but generally bad outcome over 8 years , the disease result ing in high levels of physical disability , anxiety and depression , with a high level of utilization of healthcare re sources , including joint replacement , drugs and walking aids . The results were consistent with previous suggestions that peripheral joint OA in older people is characterized by the slow acquisition of new joint sites . Progression and outcome may depend on a complex set of psychosocial factors , as well as biological ones INTRODUCTION To evaluate the efficacy of a self-management support program including a 6 week self-management course , individualised phone support and goal setting in osteoarthritis patients on a waiting list for arthroplasty surgery . METHOD R and omised controlled trial of 152 public hospital out patients awaiting hip or knee replacement surgery who were not classified as requiring urgent surgery . Participants were r and omised to a self-management program or to usual care . The primary outcome was change in the Health Education Intervention Question naire ( HeiQ ) from r and omisation to 6 month follow-up . Quality of life and depressive symptoms were also measured . Changes in pain and function were assessed using the Western Ontario and McMaster Universities ( WOMAC ) Arthritis Index . RESULTS At 6 month follow-up , health-directed behaviour was significantly greater in the intervention [ mean 4.29 , 95 % confidence interval ( CI ) 3.99 - 4.58 ] than the control ( mean 3.81 , 95 % CI 3.52 - 4.09 ; P=0.017 ) . There was also a significant effect on skill and technique acquisition for the intervention ( mean 4.37 , 95 % CI 4.19 - 4.55 ) in comparison to control ( mean 4.11 , 95 % CI 3.93 - 4.29 ; P=0.036 ) . There was no significant effect of the intervention on the remaining HeiQ subscales , WOMAC pain or disability , quality of life or depressive symptoms . DISCUSSION The arthritis self-management program improved health-directed behaviours , skill acquisition and stiffness in patients on a joint replacement waiting list , although the observed effects were of modest size ( Cohen 's d between 0.36 and 0.42 ) . There was no significant effect on pain , function or quality of life in the short term . Self-management programs can assist in maintaining health behaviours ( particularly walking ) in this patient group . Further research is needed to assess their impact on quality of life and over longer periods Background This study examined the impact of a home-based self-management intervention for housebound older adults with arthritis on the adoption of health behaviors . The moderating role of socio-demographic , psychological , and physical characteristics in the process of behavior change was also investigated . Methods Participants were 113 older adult women ( n = 102 ) and men ( n = 11 ) with osteoarthritis ( OA ) or rheumatoid arthritis ( RA ) who were r and omly assigned to experimental ( n = 68 ) or wait list control ( n = 45 ) groups . Participants were interviewed using st and ardized question naires at baseline , pre-intervention , and post-intervention . Results Adjusted multilevel modeling analyses indicated that from pre to post intervention , experimental participants significantly increased their weekly frequency of exercise and relaxation activities . Socioeconomic status and depression played a moderating role in this change for exercise with larger effects occurring among more privileged , non-depressed participants . Conclusion We conclude that a self-management intervention can successfully improve involvement in exercise and relaxation among housebound older adults with arthritis There is limited underst and ing of how comorbid health conditions affect osteoarthritis (OA)-related outcomes . This study examined associations of different comorbidity measures with baseline OA-related patient-reported outcomes ( PROs ) among patients with hip and knee OA . Data were from patients ( N = 300 , 9 % female , mean age = 61.1 ; SD = 9.2 ) enrolled in a r and omized control trial at the Durham Veterans Affairs Medical Center . Separate multivariable regression models , adjusted for demographic and clinical characteristics , examined the association of each comorbidity measure with baseline PROs : pain , physical function , depressive symptoms , fatigue , and insomnia . Comorbidity measures included the Self-Administered Comorbidity Question naire ( SACQ ) , conditions reported as activity-limiting ( SACQ-AL ) , and indicators of depression , diabetes , hypertension , and back pain . Mean ( SD ) numbers of comorbid conditions and activity-limiting conditions were 3.4 ( 1.8 ) and 1.6 ( 1.4 ) , respectively . Comorbidity scores ( SACQ overall and SACQ-AL ) and individual comorbidity conditions were each associated with worse OA-related PROs adjusting for demographic and clinical factors . Worse SACQ overall and SACQ-AL scores were associated with worse mean scores for pain , depressive symptoms , fatigue , and insomnia ( p values < 0.01 ) . Additionally , increasing SACQ-AL scores were associated with worse mean scores for function ( p < 0.01 ) . Depression was associated with worse pain ( p = 0.03 ) , fatigue , and insomnia ( p values < 0.01 ) . Diabetes was associated with worse fatigue ( p = 0.01 ) , depressive symptoms ( p = 0.02 ) , and insomnia ( p = 0.03 ) . Back pain was associated with worse pain scores ( p = 0.02 ) . Results provide evidence that comorbidity burden , particularly activity-limiting conditions , is associated with worse OA-related PROs . Interventions for patients with OA need to address comorbid conditions and their impact on key outcomes UNLABELLED A major goal of osteoarthritis ( OA ) treatment is pain management to improve function and maximise quality of life . Rofecoxib is a highly selective inhibitor of cyclooxygenase-2 used in symptomatic treatment of inflammation and pain in patients with osteoarthritis of the hip or knee . AIM The primary aim of this study was to assess the effects of rofecoxib on quality of life in elderly patients with painful osteoarthritis flares of the hip or knee , who were not responsive to or had adverse reactions to previous NSAID therapy . In addition the switch pattern of NSAIDs in these patients was recorded . METHODS A 3-week prospect i ve open label multicentre study with rofecoxib 25 mg daily in 134 male and female out patients with painful osteoarthritis flares of the knee or the hip ( mean age 69 years , SD + 8) . On day 1 the patients were all switched from their previous NSAID to rofecoxib , followed by continuous daily treatment with rofecoxib 25 mg daily over 3 weeks . On day 21 the patients discontinued daily treatment with rofecoxib and had the choice between either staying on rofecoxib , switching back to their previous NSAID , trying another NSAID or stopping drug treatment . The impact on quality of life was measured by the difference in SF-12 between day 0 and day 21 . Further endpoints included changes in self-reported pain , stiffness and functional ability as measured by the WOMAC index ( Western Ontario McMaster Universities Osteoarthritis Index ) . Correlation studies were performed between the WOMAC pain subscale and quality of life as measured by the SF-12 at baseline and over the course of the study . Patients ' report of general health status and overall assessment of pain intensity , as measured by visual analogue scale ( VAS ) , was correlated with physicians ' and patients ' assessment of the efficacy of rofecoxib treatment . RESULTS Quality of life improved with rofecoxib : the physical component summary score ( SF-12 PCS ) was improved by a statistically significant + 16.2 % ( p < 0.0001 ) after 3 weeks , while the mental health component summary score ( MCS ) was improved by + 3.0 % ( n.s . ) . Disease-specific symptoms measured by the WOMAC question naire were significantly improved under rofecoxib after 3 weeks : pain decreased by 29 % ( p < 0.0001 ) and stiffness by 25 % ( p < 0.0001 ) , while functional ability increased by 24 % ( p < 0.0001 ) . The improvement in SF-12 PCS correlated negatively with the decrease in WOMAC scores ( r = -0.54 , p < 0.0001 ; r = -0.46 , p < 0.0001 and r = -0.64 , p < 0.0001 respectively ) . General health was significantly improved by + 30.5 % ( or 15.96 mm , p < 0.0001 ) between baseline and day 21 , while pain was significantly reduced by -35.2 % ( or 17.67 mm , p < 0.0001 ) on the VAS scales . At the end of the 3-week study 75 % of the patients and 84 % of the treating physicians rated the efficacy of rofecoxib from good to excellent . Two weeks after study end the planned telephone survey revealed that 54 % of the patients preferred to stay on therapy with rofecoxib , 19 % had decided to switch back to their previous NSAID ( this observation being most marked for diclofenac , where 38 % of initial diclofenac patients had decided to switch back to their initial therapy ) , 9 % had been switched to another NSAID and 7.5 % had discontinued treatment . The switch pattern is unknown in the remaining 7.5 % . CONCLUSION Rofecoxib significantly improves quality of life , as measured by the SF-12 , in OA patients who were either unresponsive to or presented with adverse reactions to previous NSAID therapy ( including celecoxib ) . In addition , rofecoxib significantly improved pain , stiffness and function , as assessed by the WOMAC question naire BACKGROUND pain is the leading symptom of osteoarthritis ( OA ) and is often chronic in nature , leading to significant morbidity and decreased quality of life . Duloxetine , a selective serotonin norepinephrine reuptake inhibitor has been demonstrated to have a central ly acting analgesic effect . OBJECTIVES the aim of the present study was to investigate the efficacy of duloxetine in reducing pain in older adults with knee OA . METHODS totally , 288 patients aged 65 years and above with primary knee OA were enrolled in this study . Patients were r and omised 1:1 . Totally , 144 received 60 mg/day of duloxetine HCL and 144 received placebo for 16 weeks . Outcome measures included pain reduction and improvement in physical functioning scores . Pain was assessed using the visual analogue pain scale ( VAS ; 0 - 100 mm ) . The Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) scores were used to assess function . RESULTS two-hundred and seventy four of the 288 patients completed the study . There was a statistically significant reduction in pain and a significant improvement in WOMAC scores at 16 weeks in the duloxetine group versus the placebo group . No serious side effects were reported . CONCLUSIONS the findings of the present study provide evidence for the efficacy and tolerability of duloxetine in reducing pain and subsequently improving function in older adults with knee OA . TRIAL REGISTRATION NCT01425827 AIM To explore general practitioners ' ( GPs ) management of osteoarthritis ( OA ) . BACKGROUND OA represents a large burden on primary care . Little is known about GPs ' current management of OA , especially influences on their prescribing quality care and the barriers they face while doing so . METHODS A total of 1006 GPs were r and omly selected and invited to participate in an online survey on assessment and treatment of OA , on factors influencing their management , burden on their practice , and on the need for improving care . FINDINGS There were 232 respondents ( 23 % ) . National Institute for Health and Clinical Excellence ( NICE ) guidance ( 65 % ) and professional experience ( 64 % ) were the biggest influences on OA management . When assessing patients , pain and mobility were most frequently assessed , with quality of life , independent living , sleep and depression addressed by over half of them . In all , 52 % did not use educational material s ; only a third of users rated their current educational material as good or very good . Treatments employed were largely in line with NICE recommendations . Prescription review was reported by a high proportion ( 74 % ) . Achieving adequate pain control and lack of time were the most frequently cited challenges , whereas more time with patients , collaboration with specialist colleagues and improved communication tools were the most common needs identified to improve OA management . In summary , national guidelines are an important influence for GP treatment of OA . This survey has highlighted issues about the adequacy of information available for OA , about GPs ' need for more time with OA patients and their interaction with specialist colleagues Joint lavage for knee osteoarthritis is an invasive procedure that can be stressful and painful . We aim ed to assess the impact of music therapy on perioperative anxiety , pain and tolerability of the procedure in patients undergoing joint lavage performed with two needles . We r and omized all patients diagnosed with knee osteoarthritis and undergoing joint lavage in our department from November 2009 to October 2010 to an experimental group listening to recorded music or a control group receiving no music intervention . Perioperative anxiety and pain related to the procedure were self-reported on a visual analogic scale ( 0–100 mm visual analog scale [ VAS ] ) , and heart rate and blood pressure were measured during the procedure . Tolerability was assessed on a four- grade scale directly after the procedure . We included 62 patients ( 31 in each group ) . Mean age was 68.8 ± 12.6 years ( 72 % females ) . As compared with the control group , the music group had lower levels of perioperative anxiety ( 40.3 ± 31.1 vs. 58.2 ± 26.3 mm ; p = 0.046 ) and pain related to the procedure ( 26.6 ± 16.2 vs. 51.2 ± 23.7 mm ; p = 0.0005 ) . Moreover , heart rate was lower in the music group ( 69.5 ± 11.4 vs. 77.2 ± 13.2 ; p = 0.043 ) but not diastolic or systolic blood pressure . Tolerability was higher in the music group ( p = 0.002 ) . Music is a simple and effective tool to alleviate pain and anxiety in patients undergoing joint lavage for knee osteoarthritis OBJECTIVE The intent of this cross-sectional study was to broaden the range of variables examined in relationship to depression in osteoarthritis ( OA ) to include comorbidity , stressful life events , and the ways people respond to their disease . We examined the relationship of coping behaviors and perceptions , and medical treatments received for OA and depressive symptoms . METHODS In the fifth year of a prospect i ve cohort study , 1227 individuals > or= 62 years of age with hip/knee OA provided information about sociodemographics ( age , sex , living circumstances , education ) , arthritis severity ( WOMAC pain and function ; ClinHAQ fatigue ) , comorbidity , life events , coping behavior , coping efficacy , treatment ( pain management , treatment for depression ) , and depressed mood ( Centre for Epidemiological Studies Depression scale , CES-D ) . Using hierarchical linear regression , variables were entered in blocks to predict CES-D scores . In the final block , the interaction of coping behavior and coping efficacy was tested . RESULTS The response rate was 82.4 % ( n = 1227/1489 ) . The mean CES-D score was 9.4 , with 21.3 % of individuals scoring > or= 16 ( supporting depressed mood ) . Higher level of depressed mood was independently and significantly associated with being female , experiencing greater pain and fatigue , experiencing stressful life events , more coping behaviors , receiving treatment for depression/mental illness , and a coping behavior by coping efficacy interaction , with 63.4 % of the variance accounted for in the model . CONCLUSION Among older adults with OA , the prevalence of depressive symptoms is high . Longitudinal studies must consider OA management strategies , including both the amount of behavioral coping and its perceived efficacy , to eluci date potential interventions design ed to reduce depression in patients with OA OBJECTIVE To investigate the impact of video information on preoperative anxiety of patients scheduled to undergo joint lavage for knee osteoarthritis , and tolerability of the lavage . METHODS A video film on joint lavage ( duration 4 minutes , 20 seconds ) was made by medical communication professionals , based on recommendations of the medical and paramedical staff of the Institute of Rheumatology . Patients diagnosed with knee osteoarthritis and scheduled for lavage were assigned , using a preestablished list of r and omization , to either the video group or the no-video group . In the operating room , preoperative anxiety level was measured on a 100-mm visual analog scale ( VAS ) , and tolerability was assessed using a 4- grade scale . RESULTS One hundred twelve patients ( 56 patients in each group ) were included and completed the trial . Preoperative anxiety was lower by half for patients who had viewed the video ( VAS 13 + /- 20 versus 26 + /- 27 ; P = 0.0056 ) . Tolerability of knee lavage was also significantly better in the video group ( very tolerable 91 % versus 48 % ; P < 0.0001 ) . CONCLUSION This prospect i ve , controlled , r and omized study confirms the usefulness of video information prior to an invasive rheumatology procedure Abstract Objective To evaluate clinical effectiveness of a self management programme for arthritis in patients in primary care with osteoarthritis . Design R and omised controlled trial . Setting 74 general practice s in the United Kingdom . Participants 812 patients aged 50 and over with osteoarthritis of hips or knees ( or both ) and pain or disability ( or both ) . Intervention Participants were r and omised to six sessions of self management of arthritis and an education booklet ( intervention group ) or the education booklet alone ( control group ) . Main outcome measures Primary outcome was quality of life , as assessed by the short form health survey ( SF-36 ) . Several other physical and psychosocial secondary outcomes were assessed . Data were collected at baseline , four months , and 12 months . Results Response rates were 80 % and 76 % at four and 12 months . The two groups showed significant differences at 12 months on the anxiety subscore of the hospital anxiety and depression scale ( mean difference −0.62 , 95 % confidence interval −1.08 to −0.16 ) , arthritis self efficacy scale for pain ( 0.98 , 0.07 to 1.89 ) , and self efficacy for other aspects of management ( 1.58 , 0.25 to 2.90 ) . Results were similar for intention to treat and per protocol analyses . No significant difference was seen in number of visits to the general practitioner at 12 months . Conclusions The self management of arthritis programme reduced anxiety and improved participants ' perceived self efficacy to manage symptoms , but it had no significant effect on pain , physical functioning , or contact with primary care . Trial registration Current Controlled Trials IS RCT N79115352 [ controlled-trials.com ] SUMMARY Methods : An open-label multicentre study was conducted in primary care centres in Spain to investigate the effect of a switch from celecoxib to rofecoxib among patients with osteoarthritis and to identify factors associated with a good response to rofecoxib treatment . Patients were eligible to participate in this study if their physicians considered that they might benefit from such a change of therapy . A total of 2228 patients ( 1481 women ) were enrolled in the study : participants ' mean age was 66.37 years ( SD 9.04 ) . Mean duration of OA was 7.44 ( 6.38 ) years . Predominant sites of OA included the knee ( 1132 patients , 50.8 % ) , lumbar spine ( 977 patients , 43.9 % ) and cervical spine ( 739 patients , 33.2 % ) . At baseline , most patients ( 77 % ) were being prescribed celecoxib 200 mg/day ; during the study most ( 92.5 % ) received rofecoxib 25 mg/day . The mean interval between switch to rofecoxib and follow-up interview was 33 days . Principal results : Patients considered the therapeutic response to rofecoxib substantially and significantly superior to that previously obtained with celecoxib for the management of OA-related pain and OA-related health status ( p < 0.001 ) . Seventy-two percent of patients classified their response to rofecoxib therapy as ' good ' or ' very good ' ( vs 6.6 % of patients at baseline with celecoxib ) and 89.3 % of patients expressed satisfaction with rofecoxib ( vs 28.9 % at baseline with celecoxib ) . Improvements reported in patient self- assessment s following rofecoxib therapy were complemented by similar changes in physician perceptions . The number of patients considered by their doctors to have ' good ' or ‘ very good ’ OA-related health status rose from 10.1 % at baseline to 80.0 % on completion of rofecoxib therapy . Ancillary indices such as the proportion of patients with self-reported depression were also favourably influenced by the switch to rofecoxib from celecoxib . Determinants of response : Patient characteristics identified in multivariate analysis as predictive of a favourable response to rofecoxib comprised age , obesity , depression , diabetes and OA-related overall health status . Conclusions : The results of this observational study indicate that rofecoxib 25 mg/day is likely to be more effective in patients with OA who do not respond well to celecoxib 200 mg/day and satisfies a large proportion of both patients and physicians . These data are of practical interest because they indicate that , at the doses most often used in primary practice in Spain to treat OA , many patients who are dissatisfied with the effects of celecoxib 200 mg/day may benefit from a switch to rofecoxib 25 mg/day . The data obtained in this study also reveal that younger OA patients with relatively uncomplicated clinical circumstances ( a population in which use of Coxibs is relatively low at present ) are likely to derive substantial benefit from a switch to rofecoxib therapy OBJECTIVE Collaborative care for depression decreases arthritis pain and disability among older adults , above and beyond mood improvement . This study investigates whether depression management is effective for improving arthritis outcomes across a range of pain severity and activity interference . METHODS A multi-site r and omized-controlled trial ( Improving Mood , Providing Access to Collaborative Treatment - IMPACT ) identified 1001 participants with both depression and arthritis ( mostly osteoarthritis ) . Depression care managers provided 12 months of systematic depression care [ antidepressant pharmacotherapy , and /or problem-solving treatment ( PST ) ] for intervention participants in primary care setting s. Control patients received care as usual . Baseline and 12-month interviews assessed arthritis pain severity and activity interference as well as depression , analgesic use , overall functional impairment and coexisting medical conditions . RESULTS Baseline pain severity showed significant interactions with the intervention on 12-month pain severity ( t=2.28 , df=68 , P=.03 ) and disability outcomes ( t=2.03 , df=177 , P=.04 ) . Interaction effects of the intervention with baseline activity interference on 12-month pain severity showed a similar trend , but were not statistically significant ( t=1.87 , df=944 , P=.06 ) . CONCLUSIONS Systematic depression management was more effective than usual care in decreasing pain severity among arthritis patients with lower initial pain severity , but did not have greater benefits than usual care on pain among patients with higher initial pain severity |
12,961 | 22,480,489 | Based on this evidence , the 2010 Dietary Guidelines Advisory Committee concluded that strong and consistent evidence in adults indicates that dietary patterns relatively low in energy density improve weight loss and weight maintenance .
In addition , the committee concluded that there was moderately strong evidence from method ologically rigorous longitudinal cohort studies in children and adolescents to suggest that there is a positive association between dietary energy density and increased adiposity .
This review supports a relationship between energy density and body weight in adults and in children and adolescents such that consuming diets lower in energy density may be an effective strategy for managing body weight | Energy density is a relatively new concept that has been identified as an important factor in body weight control in adults and in children and adolescents .
The Dietary Guidelines for Americans 2010 encourages consumption of an eating pattern low in energy density to manage body weight . | The energy density ( ED ; kcal/g ) of an entrée influences children 's energy intake ( EI ) , but the effect of simultaneously changing both ED and portion size of an entrée on preschool children 's EI is unknown . In this within-subject crossover study , 3- to 5-year-old children ( 30 boys , 31 girls ) in a daycare facility were served a test lunch once/week for 4 weeks . The amount and type of vegetables and cheeses incorporated into the sauce of a pasta entrée were manipulated to create two versions that varied in ED by 25 % ( 1.6 or 1.2 kcal/g ) . Across the weeks , each version of the entrée was served to the children in each of two portion sizes ( 400 or 300 g ) . Lunch , consumed ad libitum , also included carrots , applesauce , and milk . Decreasing ED of the entrée by 25 % significantly ( P<0.0001 ) reduced children 's EI of the entrée by 25 % ( 63.1+/-8.3 kcal ) and EI at lunch by 17 % ( 60.7+/-8.9 kcal ) . Increasing the proportion of vegetables in the pasta entrée increased children 's vegetable intake at lunch by half of a serving of vegetables ( P<0.01 ) . Decreasing portion size of the entrée by 25 % did not significantly affect children 's total food intake or EI at lunch . Therefore , reducing the ED of a lunch entrée result ed in a reduction in children 's EI from the entrée and from the meal in both portion size conditions . Decreasing ED by incorporating more vegetables into recipes is an effective way of reducing children 's EI while increasing their vegetable intake Background Dietary energy density ( DED ) does not have a simple linear relationship to fat mass in children , which suggests that some children are more susceptible than others to the effects of DED . Children with the FTO ( rs9939609 ) variant that increases the risk of obesity may have a higher susceptibility to the effects of DED because their internal appetite control system is compromised . We tested the relationship between DED and fat mass in early adolescence and its interaction with FTO variants . Methods and Findings We carried out a prospect i ve analysis on 2,275 children enrolled in the Avon Longitudinal Study of Parents and Children ( ALSPAC ) . Diet was assessed at age 10 y using 3-day diet diaries . DED ( kJ/g ) was calculated excluding drinks . Children were genotyped for the FTO ( rs9939609 ) variant . Fat mass was estimated at age 13 y using the Lunar Prodigy Dual-energy X-ray Absorptiometry scanner . There was no evidence of interaction between DED at age 10 y and the high risk A allele of the FTO gene in relation to fat mass at age 13 y ( β = 0.005 , p = 0.51 ) , suggesting that the FTO gene has no effect on the relation between DED at 10 y and fat mass at 13 y. When DED at 10 y and the A allele of FTO were in the same model they were independently related to fat mass at 13 y. Each A allele of FTO was associated with 0.35±0.13 kg more fat mass at 13 y and each 1 kJ/g DED at 10 y was associated with 0.16±0.06 kg more fat mass at age 13 y , after controlling for misreporting of energy intake , gender , puberty , overweight status at 10 y , maternal education , TV watching , and physical activity . Conclusions This study reveals the multi-factorial origin of obesity and indicates that although FTO may put some children at greater risk of obesity , encouraging a low dietary energy density may be an effective strategy to help all children avoid excessive fat gain Background Experimental studies show that a reduction in dietary energy density ( ED ) is associated with reduced energy intake and body weight . However , few observational studies have investigated the role of ED on long-term weight and waist circumference change . Methods and Principal Findings This population -based prospect i ve cohort study included 89,432 participants from five European countries with mean age 53 years ( range : 20–78 years ) at baseline and were followed for an average of 6.5 years ( range : 1.9–12.5 years ) . Participants were free of cancer , cardiovascular diseases and diabetes at baseline . ED was calculated as the energy intake ( kcal ) from foods divided by the weight ( g ) of foods . Multiple linear regression analyses were performed to investigate the associations of ED with annual weight and waist circumference change . Mean ED was 1.7 kcal/g and differed across study centers . After adjusting for baseline anthropometrics , demographic and lifestyle factors , follow-up duration and energy from beverages , ED was not associated with weight change , but significantly associated with waist circumference change overall . For 1 kcal/g ED , the annual weight change was −42 g/year [ 95 % confidence interval ( CI ) : −112 , 28 ] and annual waist circumference change was 0.09 cm/year [ 95 % CI : 0.01 , 0.18 ] . In participants with baseline BMI < 25 kg/m2 , 1 kcal/g ED was associated with a waist circumference change of 0.17 cm/year [ 95 % CI : 0.09 , 0.25 ] . Conclusion Our results suggest that lower ED diets do not prevent weight gain but have a weak yet potentially beneficial effect on the prevention of abdominal obesity as measured by waist circumference This study examined the effect of energy density , independent of fat content and palatability , on food and energy intakes . With use of a within-subjects design , normal-weight women ( n = 18 ) were provided with meals for 2 d during each of three test sessions . During lunch , dinner , and an evening snack , subjects were given free access to a main entree varying in energy density ( low , medium , or high ) . The manipulated main entrees were similar in palatability to their counterparts across conditions . Low-energy compulsory ( consumption required ) side dishes accompanied each meal . Subjects also consumed a st and ard , compulsory breakfast . Results showed that subjects consumed a similar amount of food ( by weight ) across the three conditions of energy density . Thus , significantly more energy was consumed in the condition of high energy density ( 7532 + /- 363 kJ , or 1800 + /- 86 kcal ) than in the medium- ( 6356 + /- 281 kJ , or 1519 + /- 67 kcal ) and low- ( 5756 + /- 178 kJ , or 1376 + /- 43 kcal ) energy-density conditions ( P < 0.0001 ) . There were no differences in hunger or fullness before meals , after meals , or over the 2 d across conditions . The results from this study indicate that energy density affects energy intake independent of macronutrient content or palatability , suggesting that the overconsumption of high-fat foods may be due to their high energy density rather than to their fat content BACKGROUND The contribution of energy density ( ED ) of the total diet to increased risk of obesity from childhood into adolescence is unclear . OBJECTIVE We assessed the relation between the ED of the diet in childhood , calculated in a number of ways , and change in adiposity from childhood to adolescence . DESIGN In a prospect i ve study , 48 children ( 30 boys , 18 girls ) were initially studied at age 6 - 8 y ( baseline ) and followed up at age 13 - 17 y. Daily ED , energy intake , and food intake were assessed at baseline by 7-d weighed food records concurrent with estimates of total energy expenditure ( TEE ) by doubly labeled water . ED was calculated with the use of 5 published methods . Obesity risk was defined with the use of body fat from total body water by isotope dilution . Body fat was normalized for height and expressed as fat mass index ( FMI ) . Change in adiposity was calculated as follow-up FMI minus baseline FMI . RESULTS Misreporting of energy intake at the group level at baseline was low relative to the TEE . ED of the total diet at baseline by the 3 methods for calculating ED that excluded all or most beverages was prospect ively associated with change in FMI . However , ED of the total diet by any of the methods was not associated with change in the percentage body fat , body mass index , or waist circumference z scores . CONCLUSION The methods used to calculate ED and to assess obesity risk lead to different conclusions about the relation between the ED of the diet in childhood and gain in fat into adolescence BACKGROUND Consuming foods low in energy density ( kcal/g ) decreases energy intake over several days , but the effectiveness of this strategy for weight loss has not been tested . OBJECTIVE The effects on weight loss of 2 strategies for reducing the energy density of the diet were compared over 1 y. DESIGN Obese women ( n = 97 ) were r and omly assigned to groups counseled either to reduce their fat intake ( RF group ) or to reduce their fat intake and increase their intake of water-rich foods , particularly fruit and vegetables ( RF+FV group ) . No goals for energy or fat intake were assigned ; the subjects were instructed to eat ad libitum amounts of food while following the principles of their diet . RESULTS After 1 y , study completers ( n = 71 ) in both groups had significant decreases in body weight ( P < 0.0001 ) . Subjects in the RF+FV group , however , had a significantly different pattern of weight loss ( P = 0.002 ) than did subjects in the RF group . After 1 y , the RF+FV group lost 7.9 + /- 0.9 kg and the RF group lost 6.4 + /- 0.9 kg . Analysis of all r and omly assigned subjects also showed a different pattern of weight loss between groups ( P = 0.021 ) . Diet records indicated that both groups had similar reductions in fat intake . The RF+FV group , however , had a lower dietary energy density than did the RF group ( P = 0.019 ) as the result of consuming a greater weight of food ( P = 0.025 ) , especially fruit and vegetables ( P = 0.037 ) . The RF+FV group also reported less hunger ( P = 0.003 ) . CONCLUSION Reducing dietary energy density , particularly by combining increased fruit and vegetable intakes with decreased fat intake , is an effective strategy for managing body weight while controlling hunger BACKGROUND Dietary energy density ( ED ) reductions are associated with energy intake ( EI ) reductions . Little is known about influences on body weight ( BW ) . OBJECTIVES We examined the effects of behavioral interventions on ED values and explored how 6-mo ED changes relate to BW . DESIGN Prehypertensive and hypertensive persons were r and omly assigned to 1 of 3 groups : the established group received an 18-session intervention implementing well-established hypertension recommendations ( eg , weight loss , sodium reduction , and physical activity ) , the established+Dietary Approaches to Stop Hypertension ( DASH ) group received an 18-session intervention also implementing the DASH diet , and the advice group received 1 session on these topics . Two 24-h dietary recalls were collected ( n=658 ) . RESULTS Each group had significant declines in EI , ED , and BW . The established and established+DASH groups had the greatest EI and BW reductions . The established+DASH group had the greatest ED reduction and the greatest increase in the weight of food consumed . When groups were combined and analyzed by ED change tertiles , participants in the highest tertile ( ie , largest ED reduction ) lost more weight ( 5.9 kg ) than did those in the middle ( 4.0 kg ) or lowest ( 2.4 kg ) tertile . Participants in the highest and middle tertiles increased the weight of food they consumed ( 300 and 80 g/d , respectively ) but decreased their EI ( 500 and 250 kcal/d ) . Conversely , those in the lowest tertile decreased the weight of food consumed ( 100 g/d ) , with little change in EI . The highest and middle tertiles had favorable changes in fruit , vegetable , vitamin , and mineral intakes . CONCLUSION Both large and modest ED reductions were associated with weight loss and improved diet quality BACKGROUND Studies have shown that energy intake increases when both the fat content and energy density of the entire diet increases . When the fat content and energy density vary independently of one another , however , energy density , but not fat content , influences intake . OBJECTIVE The present study examined whether energy intake in lean and obese women is affected when either the energy density or the fat content of a portion of the diet is manipulated and palatability is held constant . DESIGN In a within-subjects design , 17 lean and 17 obese women consumed meals in the laboratory for four , 4-d test periods . In 3 of these test periods the energy density ( 4.4 and 6.7 kJ/g ) or the fat content ( 16 % and 36 % of energy ) of compulsory entrees representing 50 % of each subject 's usual energy intake was manipulated . Additional self-selected foods were consumed ad libitum at meals and as snacks . RESULTS There were no systematic differences in palatability of the manipulated foods across conditions . Obese and lean participants responded similarly to the dietary manipulations . Intake of self-selected foods at meals was reduced significantly by 16 % for both lean and obese subjects in the low- compared with the high-energy-density condition . The fat content of the compulsory foods had no significant effect on energy intake . Ratings of hunger did not differ between diets . CONCLUSION These results indicate that when a portion of the diet was manipulated , the energy density , but not the fat content , of the foods affected total energy intake at meals in both lean and obese women BACKGROUND Little is known about the long-term effects of dietary energy density ( ED ) on weight gain . OBJECTIVE The objective was to assess the long-term relation between changes in dietary ED and age-related weight gain . DESIGN We conducted a prospect i ve study of 50 026 women ( x + /- SD age : 36.5 + /- 4.6 y ) in the Nurses ' Health Study II followed from 1991 to 1999 . Dietary ED and body weight were ascertained in 1991 , 1995 , and 1999 . Total dietary ED was calculated by dividing each subject 's daily energy intake ( kcal ) by the reported weight ( g ) of all foods consumed . RESULTS Dietary ED was positively correlated with saturated fat ( r = 0.16 ) , trans fat ( r = 0.15 ) , and the glycemic index ( r = 0.16 ) , but was inversely correlated with vegetable protein ( r = -0.30 ) , vegetables ( r = -0.27 ) , and fruit ( r = -0.17 ) . ED was not significantly correlated with total fat intake as a percentage of energy ( r = 0.08 ) . Women who increased their dietary ED during follow-up the most ( 5th quintile ) had a significantly greater multivariate-adjusted weight gain than did those who decreased their dietary ED ( 1st quintile ) ( 8-y time period : 6.42 kg compared with 4.57 kg ; P for trend < 0.001 ) . However , the amount of weight change over time varied considerably according to the ED values of individual foods and beverages . CONCLUSION A high dietary ED reflects a dietary pattern higher in saturated and trans fats and refined carbohydrates . Increases in dietary ED were associated with greater weight gain among middle-aged women during 8 y of follow-up . However , public health recommendations can not be made simply on the basis of ED values of individual foods and beverages BACKGROUND When the portion size and energy density ( in kcal/g ) of a food are varied simultaneously in a single meal , each influences energy intake independently . OBJECTIVE We aim ed to determine how the effects of portion size and energy density combine to influence energy intake and satiety over multiple meals for 2 d. DESIGN In a crossover design , 24 young women were provided with meals and snacks for 2 consecutive days per week for 4 wk ; all foods were consumed ad libitum . Across the 4 sessions , the subjects were served the same 2 daily menus , but all foods were varied in portion size and energy density between a st and ard level ( 100 % ) and a reduced level ( 75 % ) . RESULTS Reducing the portion size and energy density of all foods led to significant and independent decreases in energy intake over 2 d ( P < 0.0001 ) . A 25 % decrease in portion size led to a 10 % decrease in energy intake ( 231 kcal/d ) , and a 25 % decrease in energy density led to a 24 % decrease in energy intake ( 575 kcal/d ) . The effects on energy intake were additive and were sustained from meal to meal . Despite the large variation in energy intake , there were no significant differences in the ratings of hunger and fullness across conditions over the 2 d. CONCLUSIONS Reductions in portion size and energy density independently decreased ad libitum energy intake in women when commonly consumed foods were served over 2 d. Reductions in both portion size and energy density can help to moderate energy intake without increased hunger This study examines the combined effects of caloric restriction on body composition , blood lipid , and satiety in slightly overweight women by varying food density and aerobic exercise . Twenty-three women were r and omly assigned to one of two groups for a four-week weight management program : the high-energy density diet plus exercise ( HDE : n = 12 , 22 ± 2 yrs , 65 ± 7 kg , 164 ± 5 cm , 35 ± 4 % fat ) and low-energy density diet plus exercise ( LDE : n = 11 , 22 ± 1 yrs , 67 ± 7 kg , 161 ± 2 cm , 35 ± 4 % fat ) groups . Subjects maintained a low-calorie diet ( 1,500 kcal/day ) during the program . Isocaloric ( 483 ± 26 for HDE , 487 ± 27 kcal for LDE ) but different weight ( 365 ± 68 for HDE , 814 ± 202 g for LDE ) of lunch was provided . After lunch , they biked at 60 % of maximum capacity for 40 minutes , five times per week . The hunger level was scaled ( 1 : extremely hungry ; 9 : extremely full ) at 17:30 each day . Before and after the program , the subjects ' physical characteristics were measured , and fasting blood sample s were drawn . The daily energy intake was 1,551 ± 259 for HDE and 1,404 ± 150 kcal for LDE ( P > 0.05 ) . After four weeks , the subjects ' weights and % fat decreased for both LDE ( -1.9 kg and -1.5 % , P < 0.05 ) and HDE ( -1.6 kg and -1.4 % , respectively , P < 0.05 ) . The hunger level was significantly higher for HDE ( 2.46 ± 0.28 ) than for LDE ( 3.10 ± 0.26 ) ( P < 0.05 ) . The results suggest that a low-energy density diet is more likely to be tolerated than a high-energy density diet for a weight management program combining a low-calorie diet and exercise , mainly because of a reduced hunger sensation Background : Consumption of snacks might contribute to the obesity epidemic . It is not clear how the moment of consumption and energy density of snacks can influence the compensatory response to consumption of snacks in the long term . Objective : To investigate the effects of snack consumption for 8 weeks on changes in body weight , emphasizing on moment of consumption and energy density . Design : In total , 16 men and 66 women ( mean age 21.9 years ( s.d . 0.3 year ) , mean body mass index 20.7 kg m−2 ( s.d . 0.2 kg m−2 ) ) were r and omly assigned to one of four parallel groups in a 2 × 2 design : snacks consumed with or between meals and snacks having a low ( < 4 kJ g−1 ) or high ( > 12 kJ g−1 ) energy density . For 8 weeks , subjects consumed m and atory snacks that provided 25 % of energy requirements on each day . Body weight , body composition , physical activity level ( PAL ) and energy intake were measured in week 1 and week 8 . Results : There were no differences in changes in body weight between the four groups . Moment of consumption ( P=0.7 ) , energy density ( P=0.8 ) and interaction ( P=0.09 ) did not influence body weight . Similarly , there were no differences in changes in body composition , PAL and energy intake between the four groups . Conclusions : Body weight after 8 weeks of snack consumption was not affected by moment of consumption and energy density of snacks . This finding suggests that consuming snacks that are high or low in energy density does not necessarily contribute to weight gain . Healthy , nonobese young adults may be able to maintain a normal body weight through an accurate compensation for the consumption of snacks BACKGROUND Failure to maintain weight losses in lifestyle change programs continues to be a major problem and warrants investigation of innovative approaches to weight control . OBJECTIVE The goal of this study was to compare two novel group interventions , both aim ed at improving weight loss maintenance , with a control group . METHODS AND PROCEDURES A total of 103 women lost weight on a meal replacement-supplemented diet and were then r and omized to one of three conditions for the 14-week maintenance phase : cognitive-behavioral treatment ( CBT ) ; CBT with an enhanced food monitoring accuracy ( EFMA ) program ; or these two interventions plus a reduced energy density eating ( REDE ) program . Assessment s were conducted periodically through an 18-month postintervention . Outcome measures included weight and self-reported dietary intake . Data were analyzed using completers only as well as baseline-carried-forward imputation . RESULTS Participants lost an average of 7.6 + /- 2.6 kg during the weight loss phase and 1.8 + /- 2.3 kg during the maintenance phase . Results do not suggest that the EFMA intervention was successful in improving food monitoring accuracy . The REDE group decreased the energy density ( ED ) of their diets more so than the other two groups . However , neither the REDE nor the EFMA condition showed any advantage in weight loss maintenance . All groups regained weight between 6- and 18-month follow-ups . DISCUSSION Although no incremental weight maintenance benefit was observed in the EFMA or EFMA + REDE groups , the improvement in the ED of the REDE group 's diet , if shown to be sustainable in future studies , could have weight maintenance benefits Background Health risks linked to obesity and the difficulty most have in achieving weight loss underscore the importance of identifying dietary factors that contribute to successful weight loss . Methods This study examined the association between change in dietary energy density and weight loss over time . Subjects were 213 men and women with BMI of 30–39 kg/m2 and without chronic illness enrolled in 2004 in a r and omized trial evaluating behavioral treatments for long-term weight loss . Subjects completed a 62-item food frequency question naire at baseline and at 6 , 12 , and 18 months . Results Pearson correlations between BMI and energy density ( kcals/g of solid food ) at baseline were not significantly different from zero ( r = -0.02 , p = 0.84 ) . In a longitudinal analysis , change in energy density was strongly related to change in BMI . The estimated β for change in BMI ( kg/m2 ) of those in the quartile representing greatest decrease in energy density at 18 months compared to those in the quartile with the least was -1.95 ( p = 0.006 ) . The association was especially strong in the first six months ( estimated β = -1.43 ) , the period with greatest weight loss ( mean change in BMI = -2.50 kg/m2 from 0–6 months vs. 0.23 kg/m2 from 12–18 months ) and the greatest contrast with respect to change in energy density . Conclusion Decreased energy density predicted weight loss in this 18 month weight loss study . These findings may have important implication s for individual dietary advice and public health policies targeting weight control in the general Background Given the recognized health effects of visceral fat , the underst and ing of how diet can modulate changes in the phenotype “ waist circumference for a given body mass index ( WC BMI ) ” , a proxy measure of visceral adiposity , is deemed necessary . Hence , the objective of the present study was to assess the association between dietary factors and prospect i ve changes in visceral adiposity as measured by changes in the phenotype WC BMI . Methods and Findings We analyzed data from 48,631 men and women from 5 countries participating in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) study . Anthropometric measurements were obtained at baseline and after a median follow-up time of 5.5 years . WC BMI was defined as the residuals of waist circumference regressed on body mass index , and annual change in WC BMI ( ΔWC BMI , cm/y ) was defined as the difference between residuals at follow-up and baseline , divided by follow-up time . The association between energy , energy density ( ED ) , macronutrients , alcohol , glycemic index ( GI ) , glycemic load ( GL ) , fibre and ΔWC BMI was modelled using centre-specific adjusted linear regression , and r and om-effects meta-analyses to obtain pooled estimates . Men and women with higher ED and GI diets showed significant increases in their WC BMI , compared to those with lower ED and GI [ 1 kcal/g greater ED predicted a ΔWC BMI of 0.09 cm ( 95 % CI 0.05 to 0.13 ) in men and 0.15 cm ( 95 % CI 0.09 to 0.21 ) in women ; 10 units greater GI predicted a ΔWC BMI of 0.07 cm ( 95 % CI 0.03 to 0.12 ) in men and 0.06 cm ( 95 % CI 0.03 to 0.10 ) in women ] . Among women , lower fibre intake , higher GL , and higher alcohol consumption also predicted a higher ΔWC BMI . Conclusions Results of this study suggest that a diet with low GI and ED may prevent visceral adiposity , defined as the prospect i ve changes in WC BMI . Additional effects may be obtained among women of low alcohol , low GL , and high fibre intake In two experiments , 2 - 5-year-old children 's responsiveness to caloric density cues was examined . In a preloading protocol , consumption of fixed volumes of drinks ( 205 ml in Experiment 1 ; 150 ml in Experiment 2 ) , sweetened with sucrose , aspartame , aspartame plus low glucose maltodextrin , or a water control , was followed by ad lib consumption from among a variety of foods . Caloric drinks had about 90 kcal in Experiment 1 , 65 kcal in Experiment 2 . The delay interval between the preload and the ad lib consumption was 0 , 30 or 60 minutes . In Experiment 1 , 24 4- and 5-year-old children participated in only one delay interval , while in Experiment 2 , all 20 2- and 3-year-old children were seen in all conditions . Results revealed evidence of caloric compensation , but no evidence of preload x time delay interaction . In both experiments , aspartame also produced a significant suppression of intake relative to water , primarily due to the pattern at 30 min following the preload . Across conditions , the suppression following aspartame was usually significantly less than that produced by the caloric sweet drinks , providing evidence for postingestive effects . In Experiment 1 , suppression of intake was related to the children 's preferences for the foods , not to macronutrient content ; consumption of nonpreferred foods was most suppressed . Consumption of sweetened drinks as long as 1 hour prior to eating suppressed food intake , and this common feeding practice may also reduce dietary variety We examined the effect of dietary energy density change on body weight in participants of a r and omized trial . Intervention participants markedly increased fruit and vegetable intake while reducing energy intake from fat . Participants were 2,718 breast cancer survivors , aged 26–74 yr , with baseline mean body mass index of 27.3 kg/mm 2 ( SD = 6.3 ) . We assessed dietary intake by sets of four 24-h dietary recalls and vali date d with plasma carotenoid concentrations . Weight and height were measured at baseline , 1 yr , and 4 yr . Dietary energy density was calculated using food but excluding beverages . Intervention participants significantly reduced dietary energy density compared to controls and maintained it over 4 yr — both in cross-sectional ( P m < 0.0001 ) and longitudinal ( Group m × Time interaction , P m < 0.0001 ) analyses . Total energy intake or physical activity did not vary between groups . The intervention group had a small but significant weight loss at 1 yr ( Group m × Time interaction , P m < 0.0001 ) , but no between-group weight difference was observed at 4 yr . Our study showed that reducing dietary energy density did not result in a reduction in total energy intake and suggests that this strategy alone is not sufficient to promote long-term weight loss in a free-living population Dietary energy density ( ED ) may be a good predictor of weight gain because of its association with the regulation of appetite control signals . Among the participants of the ' SUpplementation en VItamines et Mineraux AntioXydants ' prospect i ve study , 2707 subjects were included in the present study . Changes in weight , waist circumference ( WC ) , hip circumference ( HC ) and waist : hip ratio were calculated using measured data collected in 1995/1996 and 2001/2002 . The mean changes in various anthropometric indicators according to baseline body-weight status ( BMI < or > or = 25 kg/m2 ) and sex-specific tertiles of baseline ED level or 6-year changes in ED were compared by covariance analysis . In overweight subjects , weight gain was positively associated with high dietary ED at baseline ( P for trend = 0.03 ) and with increasing ED during the follow-up ( P for trend = 0.0008 ) . Both the WC and HC changes were also positively related to baseline ED and change in ED in overweight subjects . However , the relationships observed for the WC and HC changes were no longer significant after adjustment for weight change . These results support the hypothesis of a deleterious effect of high-energy-dense diets on weight change for overweight subjects . This relationship could be mediated by physical activity level . Further research needs to be performed in other population s to determine whether ED could be effective strategies to prevent weight gain OBJECTIVE The energy density ( kilocalories per gram ) of foods influences short-term energy intake . This 1-year clinical trial tested the effect on weight loss of a diet incorporating one or two servings per day of foods equal in energy but differing in energy density . RESEARCH METHODS AND PROCEDURES Dietitians instructed 200 overweight and obese women and men to follow an exchange-based energy-restricted diet . Additionally , subjects were r and omized to consume daily either one or two servings of low energy-dense soup , two servings of high energy-dense snack foods , or no special food ( comparison group ) . RESULTS All four groups showed significant weight loss at 6 months that was well maintained at 12 months . The magnitude of weight loss , however , differed by group ( p=0.006 ) . At 1 year , weight loss in the comparison ( 8.1+/-1.1 kg ) and two-soup ( 7.2+/-0.9 kg ) groups was significantly greater than that in the two-snack group ( 4.8+/-0.7 kg ) ; weight loss in the one-soup group ( 6.1+/-1.1 kg ) did not differ significantly from other groups . Weight loss was significantly correlated with the decrease in dietary energy density from baseline at 1 and 2 months ( p=0.0001 ) but not at 6 and 12 months . DISCUSSION On an energy-restricted diet , consuming two servings of low energy-dense soup daily led to 50 % greater weight loss than consuming the same amount of energy as high energy-dense snack food . Regularly consuming foods that are low in energy density can be an effective strategy for weight management OBJECTIVE We examined whether associations between dietary components and , in particular , energy density ( ED ) predicted subsequent 5-year weight changes . RESEARCH METHODS AND PROCEDURES The present longitudinal population study was part of the Danish World Health Organization Multinational Monitoring of Trends and Determinants in Cardiovascular Disease ( MONICA ) and the 1936 cohort dietary studies . Effects of components were studied in relation to subsequent 5-year weight changes in 862 men and 900 women , 30 to 60 years old . Linear multiple regression analyses were conducted . RESULTS Mean 5-year changes in body weight ( BW ) were 1.2 + /- 3.9 and 1.3 + /- 4.6 kg for men and women , respectively . In general , neither ED nor any of the dietary components was associated with subsequent change in BW . In women , ED was positively associated with weight gain among the obese ( BMI > 30 kg/m2 ) and inversely associated with weight gain in normal-weight women ( BMI < 25 kg/m2 ) ( p = 0.01 ) . However , in men there was a non-significant inverse trend between ED and weight gain in the obese and no significant interaction . DISCUSSION To our knowledge , this is the first prospect i ve study to examine the associations between ED and subsequent changes in BW , and despite a general belief that ED is a major determinant of obesity , the present study did not generally lend support for an association . However , among certain subgroups , an energy-dense diet may be a risk factor for weight development This study evaluated the effect of adding fruit or oats to the diet of free-living women on energy consumption and body weight . Fruit and oat cookies had the same amount of fiber and total calories ( approximately 200 kcal ) , but differed in energy density . We analyzed data from a clinical trial conducted in a primary care unit in Rio de Janeiro , Brazil . Forty-nine women , ages ranging from 30 to 50 years , with body mass index ( BMI ) > 25 kg/m2 , were r and omly chosen to add three apples ( 0.63 kcal/g energy density ) or three pears ( 0.64 kcal/g energy density ) or three oat cookies ( 3.7 kcal/g energy density ) to their usual diet for 10 weeks . Fiber composition was similar ( approximately 6 g ) . Statistical analysis of the repeated measures of dietary composition and body weight were analyzed using mixed model procedures . Results showed a significant decrease in the energy density during the follow-up ( -1.23 kcal/g , p<0.04 , and -1.29 kcal/g , p<0.05 ) for apples and pears , respectively , compared to the oat group . The energy intake also decreased significantly ( -25.05 and -19.66 kcal/day ) for the apple and pear group , respectively , but showed a small increase ( + 0.93 ) for the oat group . Apples and pears were also associated ( p<0.001 ) with weight reduction ( -0.93 kg for the apple and -0.84 for the pear group ) , whereas weight was unchanged ( + 0.21 ; p=0.35 ) in the oat group . Results suggest that energy densities of fruits , independent of their fiber amount can reduce energy consumption and body weight over time OBJECTIVE We tested the effect on meal intake of varying the energy density and portion size of a compulsory first-course salad . DESIGN The study used a r and omized crossover design . SUBJECTS/ SETTING Forty-two women from the State College , PA , university community ate lunch in the laboratory once per week for 7 weeks . INTERVENTION Lunch comprised one of six first-course salads , or no salad in the control condition , followed by a main course of pasta . Subjects were required to consume the entire salad , but ate as much pasta as they wanted . The salads varied in energy density ( 0.33 , 0.67 , or 1.33 kcal/g ) and portion size ( 150 or 300 g ) . The energy density of the salad was reduced by changing the amount and type of dressing and cheese . MAIN OUTCOME MEASURES Energy intake and ratings of hunger , satiety , and food characteristics were measured . STATISTICAL ANALYSES PERFORMED Outcomes were analyzed using a linear mixed model with repeated measures . RESULTS Compared with having no first course , consuming the low-energy-dense salads reduced meal energy intake ( by 7 % for the small portion and 12 % for the large ) , and consuming the high-energy-dense salads increased intake ( by 8 % for the small portion and 17 % for the large ) . When two salads with the same number of calories were compared , meal intake was decreased when the large portion of the lower-energy-dense salad was consumed . CONCLUSIONS Eating a low-energy-dense first course enhances satiety and reduces meal energy intake . Consuming a large portion of a low-energy-dense food at the start of a meal may be an effective strategy for weight management |
12,962 | 25,824,957 | The most frequently reported indicators of implementation success were fidelity and coverage .
Determinants related to the social-political context and the organization were most often cited as influencing implementation , in particular , ' collaboration between community partners ' , ' the availability of ( human ) re sources ' and ' time available for implementation ' .
The association between determinants and implementation variability was never explicated . | The implementation of intersectoral community approaches targeting childhood obesity ( IACO ) is considered challenging .
To help overcome these challenges , an overview of the evidence to date is needed . | BACKGROUND Many critical appraisal tools ( CATs ) exist for which there is little or no information on development of the CAT , evaluation of validity , or testing reliability . The proposed CAT was developed based on a number of other CATs , general research methods theory , and reporting guidelines but requires further study to determine its effectiveness . OBJECTIVES To establish a scoring system and to evaluate the construct validity of the proposed critical appraisal tool before undertaking reliability testing . METHODS Data obtained from this exploratory study along with information on the design of the proposed CAT were combined to evaluate construct validity using the St and ards for educational and psychological testing which consist of five types of evidence : test content , response process , internal structure , relations to other variables , and consequences of testing . To obtain data for internal structure and relations to other variables , the proposed CAT was analysed against five alternative CATs . A r and om sample of 10 papers from six different research design s across the range of health related research were selected , giving a total sample size of 60 papers . RESULTS In all research design s , the proposed CAT had significant ( p<0.05 , two-tailed ) weak to moderate positive correlations ( Kendall 's τ 0.33 - 0.55 ) with the alternative CATs , except in the Preamble category . There were significant moderate to strong positive correlations in the quasi-experimental ( τ 0.70 - 1.00 ) , descriptive/exploratory/observational ( τ 0.72 - 1.00 ) , qualitative ( τ 0.74 - 0.81 ) , and systematic review ( τ 0.62 - 0.82 ) design s and to a lesser extent in the true experimental ( τ 0.68 - 0.70 ) design . There were no significant correlations in the single system research design s. CONCLUSIONS Based on the results obtained , the theory on which the proposed CAT was design ed , and the objective of the proposed CAT there was enough evidence to show that inferences made from scores obtained from the proposed CAT should be sound Background The prevalence of obesity increased while certain measures of physical fitness deteriorated in preschool children in China over the past decade . This study tested the effectiveness of a multifaceted intervention that integrated childcare center , families , and community to promote healthy growth and physical fitness in preschool Chinese children . Methods This 12-month study was conducted using a quasi-experimental pretest/posttest design with comparison group . The participants were 357 children ( mean age = 4.5 year ) enrolled in three grade levels in two childcare centers in Beijing , China . The intervention included : 1 ) childcare center intervention ( physical activity policy changes , teacher training , physical education curriculum and food services training ) , 2 ) family intervention ( parent education , internet website for support , and family events ) , and 3 ) community intervention ( playground renovation and community health promotion events ) . The study outcome measures included body composition ( percent body fat , fat mass , and muscle mass ) , Body Mass Index ( BMI ) and BMI z-score and physical fitness scores in 20-meter agility run ( 20M-AR ) , broad jump for distance ( BJ ) , timed 10-jumps , tennis ball throwing ( TBT ) , sit and reach ( SR ) , balance beam walk ( BBW ) , 20-meter crawl ( 20M-C ) ) , 30-meter sprint ( 30M-S ) ) from a norm referenced test . Measures of process evaluation included monitoring of children ’s physical activity ( activity time and intensity ) and food preparation records , and fidelity of intervention protocol implementation . Results Children in the intervention center significantly lowered their body fat percent ( −1.2 % , p < 0.0001 ) , fat mass ( −0.55 kg , p < 0.0001 ) , and body weight ( 0.36 kg , p < 0.02 ) and increased muscle mass ( 0.48 kg , p < 0.0001 ) , compared to children in the control center . They also improved all measures of physical fitness except timed 10-jumps ( 20M-AR : −0.74 seconds , p < 0.0001 ; BJ : 8.09 cm , p < 0.0001 ; TBT : 0.52 meters , p < 0.006 ; SR : 0.88 cm , p < 0.03 ; BBW : −2.02 seconds , p < 0.0001 ; 30M-S : −0.45 seconds , p < 0.02 ; 20M-C : −3.36 seconds , p < 0.0001 ) . Process evaluation data showed that the intervention protocol was implemented with high fidelity . Conclusions The study demonstrated that a policy-driven multi-faceted intervention can improve preschool children ’s body composition and physical fitness . Program efficacy should be tested in a r and omized trial . Trial registration ChiCTR-ONRC-14004143 Excess weight gain in American Indian/Alaskan native ( AI/AN ) children is a public health concern . This study tested ( 1 ) the feasibility of delivering community-wide interventions , alone or in combination with family-based interventions , to promote breastfeeding and reduce the consumption of sugar-sweetened beverages ; and ( 2 ) whether these interventions decrease Body Mass Index ( BMI ) -Z scores in children 18–24 months of age . Three AI/AN tribes were r and omly assigned to two active interventions ; a community-wide intervention alone ( tribe A ; n = 63 families ) or community-wide intervention containing a family component ( tribes B and C ; n = 142 families ) . Tribal staff and the research team design ed community-tailored interventions and trained community health workers to deliver the family intervention through home visits . Feasibility and acceptability of the intervention and BMI -Z scores at 18–24 months were compared between tribe A and tribes B & C combined using a separate sample pretest , posttest design . Eighty-six percent of enrolled families completed the study . Breastfeeding initiation and 6-month duration increased 14 and 15 % , respectively , in all tribes compared to national rates for American Indians . Breastfeeding at 12 months was comparable to national data . Parents expressed confidence in their ability to curtail family consumption of sugar-sweetened beverages . Compared to a pretest sample of children of a similar age 2 years before the study begun , BMI -Z scores increased in all tribes . However , the increase was less in tribes B & C compared to tribe A ( −0.75 , P = 0.016 ) . Family , plus community-wide interventions to increase breastfeeding and curtail sugar-sweetened beverages attenuate BMI rise in AI/AN toddlers more than community-wide interventions alone In systematic review s , evidence -based practice and journal clubs critical appraisal tools are used to rate research papers . However , little evidence exists on whether the critical appraisal tool , subject matter knowledge or research design knowledge affect the appraisal of research papers . A match paired r and omised trial was conducted in August/September 2010 in the Faculty of Medicine , Health and Molecular Science , James Cook University , Australia . Ten participants in total were r and omly assigned to two groups using either an informal appraisal of research ( IA group ) or the Crowe Critical Appraisal Tool ( CCAT group ) , a general critical appraisal tool . Participant independently appraised five research papers , where each paper had a different research design . The scores allocated to the papers by each group were analysed . The intraclass correlation coefficient for absolute agreement was 0.76 for the informal appraisal group and 0.88 for the Crowe Critical Appraisal Tool group . The G study showed that in the informal appraisal group 24 % of variance in scores was attributable to either the rater or paper × rater interactions , whereas this was 12 % in the Crowe Critical Appraisal Tool group . Analysis of covariance showed that there were statistically significant results in the informal appraisal group for subject matter knowledge ( F(1,18 ) = 7.03 , P < 0.05 1 tailed , partial η² = 0.28 ) and rater ( F(4,18 ) = 4.57 , P < 0.05 1 tailed , partial η² = 0.50 ) . Kendall 's tau correlation coefficient also showed a significant weak positive relationship ( τ = 0.38 , P = 0.03 ) between total score and subject matter knowledge for the informal appraisal group . The Crowe Critical Appraisal Tool was more reliable than an informal appraisal of the research papers . In the informal appraisal group , there were significant effects for rater and subject matter knowledge , whereas the Crowe Critical Appraisal Tool almost eliminated the rater effect , and no subject matter knowledge effect was apparent . There was no research design knowledge effect in either group . The Crowe Critical Appraisal Tool provided much better score reliability and should help readers with different levels and types of knowledge to reach similar conclusions about a research paper THE R AND OMIZED controlled trial ( RCT ) , more than any other methodology , can have a powerful and immediate impact on patient care . Ideally , the report of such an evaluation needs to convey to the reader relevant information concerning the design , conduct , analysis , and generalizability of the trial . This information should provide the reader with the ability to make informed judgments regarding the internal and external validity of the trial . Accurate and complete reporting also benefits editors and review ers in their deliberations regarding su bmi tted manuscripts . For RCTs to ultimately benefit patients , the published report should be of the highest possible st and ard OBJECTIVE To examine the reliability of scores obtained from a proposed critical appraisal tool ( CAT ) . STUDY DESIGN AND SETTING Based on a r and om sample of 24 health-related research papers , the scores from the proposed CAT were examined using intraclass correlation coefficients ( ICCs ) , generalizability theory , and participants ' feedback . RESULTS The ICC for all research papers was 0.83 ( consistency ) and 0.74 ( absolute agreement ) for four participants . For individual research design s , the highest ICC ( consistency ) was for qualitative research ( 0.91 ) and the lowest was for descriptive , exploratory and observational research ( 0.64 ) . The G study showed a moderate research design effect ( 32 % ) for scores averaged across all papers . The research design effect was mainly in the Sampling , Results , and Discussion categories ( 44 % , 36 % , and 34 % , respectively ) . The scores for research design s showed a majority paper effect for each ( 53 - 70 % ) , with small to moderate rater or paper × rater interaction effects ( 0 - 27 % ) . CONCLUSIONS Possible reasons for the research design effect were that the participants were unfamiliar with some of the research design s and that papers were not matched to participants ' expertise . Even so , the proposed CAT showed great promise as a tool that can be used across a wide range of research design OBJECTIVE Document the impact of Let 's Go ! , a multi setting community-based childhood obesity prevention program on participants in 12 communities in Maine . METHODS The study used repeated r and om telephone surveys with 800 parents of children to measure awareness of messages and child behaviors . Surveys were conducted in schools , child care programs , and afterschool programs to track changes in policies and environments . RESULTS Findings show improvements from 2007 to 2011 : Children consuming fruits and vegetables increased from 18 % , 95 % CI [ 15 , 21 ] , to 26 % [ 23 , 30 ] ( p < .001 ) ; children limiting sugary drinks increased from 63 % [ 59 , 67 ] to 69 % [ 65 , 73 ] ( p = .011 ) ; and parent awareness of the program grew from 10 % [ 7 , 12 ] to 47 % [ 43 , 51 ] ( p < .001 ) . Participating sites implemented widespread changes to promote healthy behaviors . CONCLUSIONS A multi setting , community-based intervention with a consistent message can positively impact behaviors that lead to childhood obesity |
12,963 | 26,791,177 | Evidence to date shows that acute exposure to food advertising increases food intake in children but not in adults .
These data support public health policy action that seeks to reduce children 's exposure to unhealthy food advertising | BACKGROUND Several studies have assessed the effects of food and nonalcoholic beverage ( hereafter collectively referred to as food ) advertising on food consumption , but the results of these studies have been mixed .
This lack of clarity may be impeding policy action .
OBJECTIVE We examined the evidence for a relation between acute exposure to experimental unhealthy food advertising and food consumption . | BACKGROUND The effect of television viewing ( TVV ) with and without advertisements ( ads ) on energy intake is unclear . OBJECTIVE The objectives were to test 1 ) the effect of TVV , with and without ads , on energy intake compared with a control and reading condition and 2 ) the association of distractibility and memory for ads with energy intake and body weight . DESIGN Forty-eight ( 26 female ) adults ( age : 19 - 54 y ) with a body mass index ( in kg/m(2 ) ) of 20 - 35 completed this laboratory-based study . All participants completed 4 buffet-style meals in r and om order in the following conditions : 1 ) control , 2 ) while reading , 3 ) while watching TV with food and nonfood ads ( TV-ads ) , and 4 ) while watching TV with no ads ( TV-no ads ) . Energy intake was quantified by weighing foods . Distractibility and memory for ads in the TV-ads condition were quantified with a norm-referenced test and recognition task , respectively . RESULTS Repeated- measures analysis of variance indicated that energy and macronutrient intake did not differ significantly among the 4 conditions ( P > 0.65 ) . Controlling for sex , memory for ads was associated with body weight ( r = 0.36 , P < 0.05 ) and energy intake but only when viewing TV ( r = 0.39 , P < 0.05 during the TV-no ads condition , and r = 0.29 , P = 0.06 during the TV-ads condition ) . Controlling for sex , distractibility was associated with body weight ( r = 0.36 , P < 0.05 ) but not energy intake . Distractibility , however , accounted for 13 % of the variance in men 's energy intake ( P = 0.11 ) . CONCLUSIONS TVV did not affect energy intake , but individual characteristics ( memory for ads ) were associated with body weight and energy intake in certain conditions . These characteristics should be considered in food intake and intervention studies Television viewing may contribute to obesity via promotion of sedentary behavior and exposure to food-related commercials . However , the mechanisms by which food-related commercials promote food intake are not well understood . Therefore , the purpose of the present study was to examine the impact of television advertisements on food intake according to sex and transportability , or the tendency to become engrossed in what one is viewing . Eighty-three undergraduate students , free of disordered eating symptoms , were stratified by sex and r and omly assigned to one of three conditions ( food-related advertisements , neutral advertisements , or no advertisements ) . They were then identified as high or low in transportability according to a median split . A significant interaction was found between advertisement condition and transportability such that those high in transportability ate more in the food than other advertisement conditions . A second interaction was found between sex and transportability with women high in transportability eating more food than women low in transportability irrespective of advertisement condition . No significant main effects of advertisement condition , sex , or transportability were found . Results suggest the importance of study ing the impact of individual difference variables on the relationship between food-related advertising and food intake BACKGROUND Previous studies have focused on the effects of television advertising on the energy intake of children . However , the rapidly changing food-marketing l and scape requires research to measure the effects of nontraditional forms of marketing on the health-related behaviors of children . OBJECTIVES The main aim of this study was to examine the effect of advergames that promote energy-dense snacks or fruit on children 's ad libitum snack and fruit consumption and to examine whether this consumption differed according to br and and product type ( energy-dense snacks and fruit ) . The second aim was to examine whether advergames can stimulate fruit intake . DESIGN We used a r and omized between-subject design with 270 children ( age : 8 - 10 y ) who played an advergame that promoted energy-dense snacks ( n = 69 ) , fruit ( n = 67 ) , or nonfood products ( n = 65 ) or were in the control condition ( n = 69 ) . Subsequently , we measured the free intake of energy-dense snacks and fruit . The children then completed question naire measures , and we weighed and measured them . RESULTS The main finding was that playing an advergame containing food cues increased general energy intake , regardless of the advertised br and or product type ( energy-dense snacks or fruit ) , and this activity particularly increased the intake of energy-dense snack foods . Children who played the fruit version of the advergame did not eat significantly more fruit than did those in the other groups . CONCLUSION The findings suggest that playing advergames that promote food , including either energy-dense snacks or fruit , increases energy intake in children This study examined the potential moderating role of attentional bias ( i.e. , gaze duration , number of fixations , latency of initial fixation ) in the effect of advergames promoting energy-dense snacks on children 's snack intake . A r and omized between-subject design was conducted with 92 children who played an advergame that promoted either energy-dense snacks or nonfood products . Eye movements and reaction times to food and nonfood cues were recorded to assess attentional bias during playtime using eye-tracking methods . Children could eat freely after playing the game . The results showed that playing an advergame containing food cues increased total intake . Furthermore , children with a higher gaze duration for the food cues ate more of the advertised snacks . In addition , children with a faster latency of initial fixation to the food cues ate more in total and ate more of the advertised snacks . The number of fixations on the food cues did not increase actual snack intake . Food advertisements are design ed to grab attention , and this study shows that the extent to which a child 's attention is directed to a food cue increases the effect of the advertisement Eating behaviour is often studied in the laboratory under controlled conditions . Yet people care about the impressions others form about them so may behave differently if they feel that their eating behaviour is being monitored . Here we examined whether participants are likely to change their eating behaviour if they feel that food intake is being monitored during a laboratory study . In Study 1 participants were provided with vignettes of typical eating behaviour experiments and were asked if , and how , they would behave differently if they felt their eating behaviour was being monitored during that experiment . Study 2 tested the effect of experimentally manipulating participants ' beliefs about their eating behaviour being monitored on their food consumption in the lab . In Study 1 , participants thought they would change their behaviour if they believed their eating was being monitored and , if monitored , that they would reduce their food consumption . In Study 2 participants ate significantly less food after being led to believe that their food consumption was being recorded . Together , these studies demonstrate that if participants believe that the amount of food they eat during a study is being monitored then they are likely to suppress their food intake . This may impact the conclusions that are drawn from food intake studies |
12,964 | 30,076,965 | CAM may provide a limited short-term benefit in patients with symptom burden . | CONTEXT The aim of palliative care is to improve quality of life for patients with serious illnesses by treating their symptoms and adverse effects .
Hospice care also aims for this for patients with a life expectancy of six months or less .
When conventional therapies do not provide adequate symptom management or produce their own adverse effects , patients , families , and caregivers may prefer complementary or alternative approaches in their care .
OBJECTIVES The objectives of this study were to evaluate the available evidence on the use of complementary or alternative medicine ( CAM ) in hospice and palliative care and to summarize their potential benefits . | A r and omised controlled pilot study was carried out to examine the effects of adjunctive aromatherapy massage on mood , quality of life and physical symptoms in patients with cancer attending a specialist unit . Participants were r and omised to conventional day care alone or day care plus weekly aromatherapy massage using a st and ardised blend of oils for four weeks . At baseline and at weekly intervals , patients rated their mood , quality of life and the intensity and bother of two symptoms most important to them . Forty-six patients were recruited to the study . Due to a large number of withdrawals , only 11 of 23 ( 48 % ) patients in the aromatherapy group and 18 of 23 ( 78 % ) in the control group completed all four weeks . Mood , physical symptoms and quality of life improved in both groups . There was no statistically significant difference between groups in any of the outcome measures . Despite a lack of measurable benefit , all patients were satisfied with the aromatherapy and wished to continue . Whilst this pilot study has shown that a r and omised controlled trial of complementary therapy is feasible , it has also identified several areas that would require further consideration when design ing future studies , e.g. , the recruitment and retention of appropriate numbers of patients and the outcome measures used AIM The objective of this study was to determine whether reflexology has an impact on the quality of life of patients in the palliative stage of cancer . METHOD Twelve patients in the palliative stage of cancer with various tumour types were r and omised into two groups . They were r and omly assigned to receive either reflexology or placebo reflexology . All participants completed a linear analogue self- assessment scale relating to quality of life . All participants then received three sessions of either reflexology or placebo reflexology . The same person , a qualified reflexologist , provided the interventions for both groups . The participants were not aware of which intervention they were receiving . All participants then completed a second linear analogue self- assessment scale relating to quality of life . RESULTS All participants felt that their quality of life had improved , even those who had received the placebo treatment . The reflexology group , however , reported more benefit than the placebo group . There was a significant difference ( p = 0.004 ) between the reflexology group and the placebo group . CONCLUSION This study showed that reflexology does have an impact on the quality of life of patients in the palliative stage of cancer The Memorial Symptom Assessment Scale ( MSAS ) is a new patient-rated instrument that was developed to provide multidimensional information about a diverse group of common symptoms . This study evaluated the reliability and validity of the MSAS in the cancer population . R and omly selected in patients and out patients ( n = 246 ) with prostate , colon , breast or ovarian cancer were assessed using the MSAS and a battery of measures that independently evaluate phenomena related to quality of life . Symptom prevalence in the 218 evaluable patients ranged from 73.9 % for lack of energy to 10.6 % for difficulty swallowing . Based on a content analysis , three symptoms were deleted and two were added ; the revised scale evaluates 32 physical and psychological symptoms . A factor analysis of variance yielded two factors that distinguished three major symptom groups and several subgroups . The major groups comprised psychological symptoms ( PSYCH ) , high prevalence physical symptoms ( PHYS H ) , and low prevalence physical symptoms ( PHYS L ) . Internal consistency was high in the PHYS H and PSYCH groups ( Cronback alpha coefficients of 0.88 and 0.83 , respectively ) , and moderate in the PHYS L group ( alpha = 0.58 ) . Although the severity , frequency and distress dimensions were highly intercorrelated , canonical correlations and other analyses demonstrated that multidimensional assessment ( frequency and distress ) augments information about the impact of symptoms . High correlations with clinical status and quality of life measures support the validity of the MSAS and indicate the utility of several subscale scores , including PSYCH , PHYS , and a brief Global Distress Index . The MSAS is a reliable and valid instrument for the assessment of symptom prevalence , characteristics and distress . It provides a method for comprehensive symptom assessment that may be useful when information about symptoms is desirable , such as clinical trials that incorporate quality of life measures or studies of symptom epidemiology Visual analogue scales ( VAS ) and verbal rating scales ( VRS ) are widely used to assess pain . This paper presents a secondary analysis of a subsection of data collected as part of an evaluation of an intervention to improve nighttime pain . The aims were to describe the relationship between the VAS and VRS ; to compare characteristics of the noncompliant groups in terms of age , gender , type of surgery , and analgesics ; to explore the reasons for noncompletion of the VAS or VRS ; and to determine the noncompliance rates with each assessment scale . Worst and average pain scores were obtained for the second postoperative night for 417 patients . Fifty-nine patients ( 14.2 % ) did not complete the VAS . In contrast , two patients did not complete the VRS ( 0.5 % ) . The scores generated from the VAS and VRS correlated well , although the range of VAS scores corresponding to each VRS category was wide . We conclude that the VRS was more suitable for use in this clinical setting Many specialist palliative care services are under pressure to provide therapies such as aromatherapy , acupuncture or reflexology either by paid staff or volunteers . The evidence to justify the provision of such treatment , however , remains largely anecdotal as controlled clinical trials are difficult to design . Reflexology involves the application of pressure to ` reflex ’ areas of the h and s or feet with the intention of producing specific effects elsewhere in the body . The reflexologist palpates tender or painful areas that , it is suggested , indicate functional imbalance . As well as treatment of specific conditions , it is suggested that reflexology can relax the patient , which may aid selfhealing and prevention of disease . We have therefore conducted a pilot study with a r and omized controlled design to compare reflexology with simple foot massage The purpose of this study was to develop and test the Verran and Snyder-Halpern ( VSH ) Sleep Scale , an instrument to subjectively measure sleep characteristics . Four major sleep factors and their associated characteristics were proposed for the Sleep Scale . Subjects completed three r and omly ordered sleep question naires on three consecutive weekday mornings within the first two hours after arising . Scales included the VSH Sleep Scale , a sleep question naire and a sleep log . The VSH Sleep Scale had a reliability coefficient of .82 ( theta ) . Construct validity was examined by factor analysis and correlations between Sleep Scale items and corresponding items on the two other study instruments . Scale validity also was assessed by the known groups method . Beginning support for the validity of the VSH Sleep Scale is provided Research suggests that patients with cancer , particularly in the palliative care setting , are increasingly using aromatherapy and massage . There is good evidence that these therapies may be helpful for anxiety reduction for short periods , but few studies have looked at the longer term effects . This study was design ed to compare the effects of four-week courses of aromatherapy massage and massage alone on physical and psychological symptoms in patients with advanced cancer . Forty-two patients were r and omly allocated to receive weekly massages with lavender essential oil and an inert carrier oil ( aromatherapy group ) , an inert carrier oil only ( massage group ) or no intervention . Outcome measures included a Visual Analogue Scale ( VAS ) of pain intensity , the Verran and Snyder-Halpern ( VSH ) sleep scale , the Hospital Anxiety and Depression ( HAD ) scale and the Rotterdam Symptom Checklist ( RSCL ) . We were unable to demonstrate any significant long-term benefits of aromatherapy or massage in terms of improving pain control , anxiety or quality of life . However , sleep scores improved significantly in both the massage and the combined massage ( aromatherapy and massage ) groups . There were also statistically significant reductions in depression scores in the massage group . In this study of patients with advanced cancer , the addition of lavender essential oil did not appear to increase the beneficial effects of massage . Our results do suggest , however , that patients with high levels of psychological distress respond best to these therapies BACKGROUND The literature supporting the use of music therapy in palliative care is growing . However , the number of quantitative research studies investigating the use of music therapy in palliative care , and specifically anxiety , is limited . OBJECTIVE The aim of this research project was to examine the effectiveness of a single music therapy session in reducing anxiety for terminally ill patients . DESIGN A r and omized-controlled design was implemented and the following hypotheses tested . There will be a significant difference between the experimental and control groups on anxiety levels as demonstrated by the anxiety measurement of the Edmonton Symptom Assessment System ( ESAS ) , and heart rate . The experimental group received a single music therapy intervention and the control group received a volunteer visit . SETTING /SUBJECTS Twenty-five participants with end-stage terminal disease receiving inpatient hospice services were recruited . RESULTS The first hypothesis was supported . Results demonstrated a significant reduction in anxiety for the experimental group on the anxiety measurement of the ESAS ( p = 0.005 ) . A post hoc analysis found significant reductions in other measurements on the ESAS in the experimental group , specifically pain ( p = 0.019 ) , tiredness ( p = 0.024 ) and drowsiness ( p = 0.018 ) . The second hypothesis was not supported . CONCLUSIONS The study supports the use of music therapy to manage anxiety in terminally ill patients . Further studies are required to examine the effect of music therapy over a longer time period , as well as addressing other symptom issues Background About 90 % of patients with intra-thoracic malignancy experience breathlessness . Breathing training is helpful , but it is unknown whether repeated sessions are needed . The present study aims to test whether three sessions are better than one for breathlessness in this population . Methods This is a multi-centre r and omised controlled non-blinded parallel arm trial . Participants were allocated to three sessions or single ( 1:2 ratio ) using central computer-generated block r and omisation by an independent Trials Unit and stratified for centre . The setting was respiratory , oncology or palliative care clinics at eight UK centres . Inclusion criteria were people with intrathoracic cancer and refractory breathlessness , expected prognosis ≥3 months , and no prior experience of breathing training . The trial intervention was a complex breathlessness intervention ( breathing training , anxiety management , relaxation , pacing , and prioritisation ) delivered over three hour-long sessions at weekly intervals , or during a single hour-long session . The main primary outcome was worst breathlessness over the previous 24 hours ( ‘ worst ’ ) , by numerical rating scale ( 0 = none ; 10 = worst imaginable ) . Our primary analysis was area under the curve ( AUC ) ‘ worst ’ from baseline to 4 weeks . All analyses were by intention to treat . Results Between April 2011 and October 2013 , 156 consenting participants were r and omised ( 52 three ; 104 single ) . Overall , the ‘ worst ’ score reduced from 6.81 ( SD , 1.89 ) to 5.84 ( 2.39 ) . Primary analysis [ n = 124 ( 79 % ) ] , showed no between-arm difference in the AUC : three sessions 22.86 ( 7.12 ) vs single session 22.58 ( 7.10 ) ; P value = 0.83 ) ; mean difference 0.2 , 95 % CIs ( –2.31 to 2.97 ) . Complete case analysis showed a non-significant reduction in QALYs with three sessions ( mean difference –0.006 , 95 % CIs –0.018 to 0.006 ) . Sensitivity analyses found similar results . The probability of the single session being cost-effective ( threshold value of £ 20,000 per QALY ) was over 80 % . Conclusions There was no evidence that three sessions conferred additional benefits , including cost-effectiveness , over one . A single session of breathing training seems appropriate and minimises patient burden . Trial registration Registry : IS RCT N ; Trial registration number : IS RCT N49387307 ; http://www.is rct n.com/IS RCT N49387307 ; registration date : Purpose A pilot study to document changes in symptoms after acupuncture or nurse-led supportive care in patients with incurable cancer . Methods Patients receiving palliative care with estimated survival of at least 3 months were screened with the Edmonton Symptom Assessment System ( ESAS ) . Patients ( n=20 ) with significant symptoms were r and omised to receive weekly acupuncture or nurse-led supportive care for 4 weeks . ESAS scores were obtained before and after each treatment , and weekly for 6 weeks after treatment by telephone . Results 42 of 170 patients screened were eligible . 20 gave consent for recruitment . The compliance rate was 90 % for acupuncture and 80 % for nurse-led supportive care . Total symptom scores were reduced by an average of 22 % after each acupuncture visit and by 14 % after each supportive care visit . Compared with baseline , ESAS scores at the end of the follow-up period were reduced by 19 % for the acupuncture arm and 26 % for nurse-led supportive care . Conclusion Patients appear to benefit from incorporating acupuncture in the treatment of advanced incurable cancer . Acupuncture was well tolerated with no significant or unexpected side effects . Acupuncture had an immediate effect on all symptoms , whereas nurse-led supportive care had a larger impact 6 weeks after the final session . Both interventions appear helpful to this population and warrant further study Effective evaluation and treatment of cancer pain require valid and independent measurement of pain intensity , pain relief , and psychological distress . The Memorial Pain Assessment Card ( MPAC ) is a simple instrument design ed to provide rapid evaluation of these subjective experiences . On the 8.5 by 11 inch card are printed the eight pain intensity descriptors , and three visual analog scales which measure pain intensity , pain relief , and mood . Experienced patients can complete it in less than 20 seconds . The authors administered the MPAC to 50 hospitalized cancer patients within 48 hours of referral to the Pain Service for inadequate pain control , together with st and ard measures : The McGill Pain Question naire , Profile of Mood States , Hamilton Depression Scale , and Zung Anxiety Scale . Correlational and multiple regression analyses revealed that the MPAC can distinguish pain intensity from pain relief and from general psychological distress , and it can provide multidimensional assessment that is practically equivalent to the full assessment battery . We conclude that the MPAC is valid and effective for clinical use , and recommend it for the assessment of individual patients , and as an outcome measure in clinical trials CONTEXT Treatment of pain in palliative care patients is challenging . Adjunctive methods of pain management are desirable . Music therapy offers a nonpharmacologic and safe alternative . OBJECTIVES To determine the efficacy of a single music therapy session to reduce pain in palliative care patients . METHODS Two hundred in patients at University Hospitals Case Medical Center were enrolled in the study from 2009 to 2011 . Patients were r and omly assigned to one of two groups : st and ard care alone ( medical and nursing care that included scheduled analgesics ) or st and ard care with music therapy . A clinical nurse specialist administered pre- and post-tests to assess the level of pain using a numeric rating scale as the primary outcome , and the Face , Legs , Activity , Cry , Consolability Scale and the Functional Pain Scale as secondary outcomes . The intervention incorporated music therapist-guided autogenic relaxation and live music . RESULTS A significantly greater decrease in numeric rating scale pain scores was seen in the music therapy group ( difference in means [ 95 % CI ] -1.4 [ -2.0 , -0.8 ] ; P<0.0001 ) . Mean changes in Face , Legs , Activity , Cry , Consolability scores did not differ between study groups ( mean difference -0.3 , [ 95 % CI ] -0.8 , 0.1 ; P>0.05 ) . Mean change in Functional Pain Scale scores was significantly greater in the music therapy group ( difference in means -0.5 [ 95 % CI ] -0.8 , 0.3 ; P<0.0001 ) [ corrected ] : A single music therapy intervention incorporating therapist-guided autogenic relaxation and live music was effective in lowering pain in palliative care patients Context Some patients nearing death seek pain relief with massage , but little is known about the effectiveness of massage in managing pain in palliative care setting s. Contribution In this r and omized trial in 380 patients with advanced cancer , improvement in pain and mood immediately after treatment was greater with massage than with simple touch . Unfortunately , there were no sustained differences in pain , quality of life , or analgesic use during 3 weeks . Adverse effects were infrequent and similar in both groups . Implication Massage may offer some immediate relief for patients with advanced cancer , but the absence of sustained effects demonstrates the need for more effective strategies to manage pain at the end of life . The Editors Symptom relief is central to end-of-life care ; however , many terminally ill individuals experience serious pain and other physical and emotional symptoms ( 14 ) . Studies examining the efficacy of therapies that may mediate these symptoms deserve the highest priority . The Institute of Medicine and the National Institutes of Health recommend research directed at improving end-of-life care ( 5 , 6 ) . Pain associated with advanced cancer can cause physical and emotional distress , leading to decreased functional ability and quality of life . Massage may interrupt the cycle of distress through the therapist 's intention ( presence , communication , and desire to produce a therapeutic response ) , induction of a relaxation response , increased blood and lymphatic circulation , potentiation of analgesic effects , decreased inflammation and edema , manual release of muscle spasms , increased endogenous endorphin release , and competing sensory stimuli that override pain signals ( 711 ) . Despite theoretical bases supporting the use and growing acceptance of massage therapy , few r and omized clinical trials have assessed its efficacy . Large trials have been difficult to design and carry out ; challenges include frailty of patients with late-stage cancer and reluctance of health care providers to refer patients because of the possibility of r and omization to nonmassage therapy control ( 12 ) . Therapeutic massage can reduce pain and improve symptom distress and quality of life for patients with cancer at the end of life . The purpose of the REST ( Reducing End-of-Life Symptoms with Touch ) study was to evaluate the efficacy of massage compared with an exposure controlling for time , attention , and touch . We hypothesized that massage would decrease pain and explored effects on quality of life , physical and emotional symptom distress , and analgesic medicine use . Methods Design Overview We conducted this prospect i ve , 2-group , r and omized , single-blind trial between November 2003 and October 2006 . After we evaluated patients for inclusion and exclusion criteria , patients provided written informed consent . Then we r and omly assigned patients to a treatment group ( massage ) or control exposure ( simple touch ) . Figure 1 depicts the timing of the study procedures for a hypothetical participant . We collected individual characteristics , disease , pain characteristics , symptom distress , quality of life , functional status ( Karnofsky Performance Scale score ) ( 13 ) , expected helpfulness of massage for pain , and concurrent interventions ( pharmacologic and nonpharmacologic ) at baseline ( within 72 hours of study enrollment ) and at 3 subsequent weekly visits over the 3 to 4 weeks of participation ( sustained outcomes ) . Final data collection occurred approximately 1 week after the final treatment . Data collectors were blinded to treatment assignment . Participants received up to six 30-minute treatments over 2 weeks , with at least 24 hours between treatment sessions . The initial treatment session occurred within 48 hours of baseline data collection . The treatment provider and patient determined the scheduling of treatment sessions . Treatment providers who were not blinded to treatment assignment obtained the immediate outcomes just before and after every treatment session . All participants received routine care in addition to the specified interventions . The Colorado Multiple Institutional Review Board and , where applicable , site-specific institutional review boards approved the study . Figure 1 . Study overview : timing of study procedures . Setting and Participants Study sites included 15 U.S. hospices that are members of the Population -based Palliative Care Research Network ( PoPCRN ) ( 14 ) and the University of Colorado Cancer Center , Aurora , Colorado . Eligible participants were English-speaking adults with advanced cancer ( stage III or IV , all cancer types , any care setting ) who had at least moderate pain ( score 4 on a 0- to 10-point scale ) in the week before enrollment , an anticipated life expectancy of at least 3 weeks , and the ability to consent . Exclusion criteria included receipt of professional massage within 1 month of enrollment , anticoagulant therapy , known platelet count less than 10109 cells/L , or known unstable spine . R and omization and Interventions Verification of eligibility was forwarded by a study coordinator from each study site to the University of Colorado research ers . Two design ated investigators r and omly assigned patients ; assignments were transmitted back to the requesting site . All study personnel other than the on-site study coordinators and these 2 design ated investigators were blinded to the r and omization sequence . An SAS software program ( SAS Institute , Cary , North Carolina ) generated the r and omization sequence by producing a r and omized block design stratified by study site . Block size r and omly varied among 2 , 4 , and 6 so that it was not possible to predict the next assignment . To minimize the likelihood that potential participants would decline enrollment because of reluctance to be r and omly assigned , we offered massage after study completion to those assigned to the control group . Experimental Treatment : Massage Therapy The massage intervention included gentle effleurage , petrissage , and myofascial trigger point release . Effleurage is a smooth , gliding stroke ; petrissage is squeezing , rolling , and kneading the muscles ; and trigger point release provides concentrated finger pressure to painful localized areas in muscles to break cycles of spasm and pain ( 15 ) . Individual therapist judgment dictated the frequency of rhythm , rate , or stroke ; sequence or mix of strokes ; time spent in each stroke ; stroke length ; and body area massaged ( 16 ) . Massage therapists spent 65 % of the time in effleurage and 35 % in petrissage . The most frequently massaged areas of the body were the neck and upper back ( about 80 % of the time ) and arms , h and s , lower legs , and feet ( about 75 % of the time ) . Other areas , such as the chest , abdomen , buttocks , back of the thighs , and forehead were massaged less than 50 % of the time . Therapists appropriately modified massage in persons with skin fragility , postural limitations , edema , osteoporosis , or bone metastasis . Therapists avoided sites of inflammation or infection , hyperesthesias , injury , surgery , ports , catheters , deep venous thrombosis , and tumors . Therapists identified and treated up to 3 myofascial trigger points per session ( located 15 % to 25 % of the time in the neck , upper trapezius , and lower trapezius regions ) . One half of the sessions were provided with the patient supine , 25 % seated , and the remainder split between side-lying and prone positions . Temperature and level of privacy varied with setting . Fewer than 25 % of participants were unclothed during treatments . Massage was performed by licensed massage therapists who had at least 6 months of experience treating patients with advanced cancer or hospice patients and completed a minimum 500-hour program of study in massage from an institution recognized by their state as a vocational school . Control Exposure We design ed the control exposure , simple touch , to control for the time , attention , touch , and healing intent components of the intervention ( 17 ) . The control consisted of placement of both h and s on the participant for 3 minutes at each of the following locations bilaterally : base of neck , shoulder blades , lower back , calves , heels , clavicles , lower arms , h and s , patellae , and feet . Pressure was light and consistent , with no side-to-side h and movement . Control therapy providers interrupted conscious healing intention by silently counting backward from 100 by 7 , reciting nursery rhymes , or planning their day 's activities ( 18 , 19 ) . The control treatments were provided by individuals with no past body or energy work experience . All treatment providers participated in st and ardized h and s-on training , received a study manual and training video , and were evaluated for competency in study procedures . We monitored adherence to study protocol s during twice-yearly site visits . Treatment providers in both groups used Biotone hypoallergenic unscented massage cream ( Biotone , San Diego , California ) . For the purpose s of st and ardization and to mediate the presence of intervening variables , we did not permit music , essential oils , or energy work and instructed treatment providers to limit their communication to providing instructions or responding to therapy-related questions . To minimize variation by treatment provider , 1 primary massage therapist or simple-touch provider per participant at each study site administered study treatments . Outcomes and Follow-up We used face-to-face , interviewer-administered question naires to collect all study data . We measured neuropathic pain at baseline only by the Neuropathy Pain Scale ( 0- to 10-point scale ) , which is sensitive to pain qualities most common to neuropathic pain syndromes ( 20 , 21 ) . Presence of neuropathic pain was defined as a Neuropathy Pain Scale summary score greater than 3 . Primary Outcomes : Immediate and Sustained Change in Pain The immediate effect was measured by the pain intensity scale of the Memorial Pain Assessment Card ( MPAC ) ( 0 to 10 points ; 10 = worst pain ) ( 22 ) . The sustained effect was measured CONTEXT Certain meditation practice s may effectively address spiritual needs near end-of-life , an often overlooked aspect of quality of life ( QOL ) . Among people subject to physical isolation , meditation benefits may be blunted unless physical contact is also addressed . OBJECTIVE To evaluate independent and interactive effects of Metta meditation and massage on QOL in people with acquired immunodeficiency syndrome ( AIDS ) . DESIGN R and omized controlled blinded factorial pilot trial conducted from November 2001 to September 2003 . SETTING An AIDS-dedicated skilled nursing facility in New Haven , Connecticut . PARTICIPANTS Fifty-eight residents ( 43 % women ) with late stage disease ( AIDS or comorbidity ) . INTERVENTIONS Residents were r and omized to 1 month of meditation , massage , combined meditation and massage , or st and ard care . The meditation group received instruction , then self-administered a meditation audiocassette daily . A certified massage therapist provided the massage intervention 30 minutes per day 5 days per week . OUTCOME MEASURE Changes on Missoula-Vitas QOL Index overall and transcendent ( spiritual ) scores at 8 weeks . RESULTS The combined group showed improvement in overall ( p = 0.005 ) and transcendent ( p = 0.01 ) scores from baseline to 8 weeks , a change significantly greater ( p < 0.05 ) than the meditation , massage , and control groups . CONCLUSIONS The combination of meditation and massage has a significantly favorable influence on overall and spiritual QOL in late-stage disease relative to st and ard care , or either intervention component alone ABSTRACT Aims : In a r and omized controlled clinical trial ( RCCT ) , we examined the effects of four massages on pain intensity , prescribed IM morphine equivalent doses ( IMMSEQ ) , hospital admissions , and quality of life ( QoL ) . Methods : Of 173 referred patients , 29 ( 14 control , 15 massage ) completed this pilot study . Subjects were 69 % male and aged 63 years on average . Licensed therapists administered four , twice-weekly massages . Baseline and outcome measurements were obtained by other team members before the first and after the fourth massages . Results : Pain intensity , pulse rate , and respiratory rate were significantly reduced immediately after the massages . At study entry , the massage group reported higher pain intensity ( 2.4 ± 2.8 vs. 1.6 ± 2.1 ) which decreased by 42 % ( 1.4 ± 1.5 ) compared to a 25 % reduction in the control group ( 1.2 ± 1.3 ) ( p > .05 ) . IMMSEQ doses were stable or decreased for eight patients in each group and increased for seven massage and six control group patients . One massage group and two control group patients were hospitalized . All initial QoL scores were higher in the massage group than in the control group , but only current QoL was statistically significant . Both groups reported improved global QoL. The control group reported slight improvement in current QoL and satisfaction with QoL whereas these two aspects of QoL declined in the massage group even though their average QoL scores were higher than the control group at the end of the study . Conclusions : We demonstrated feasibility of conducting an RCCT in which we systematic ally implemented massage as a nonpharmacologic comfort therapy along with our usual hospice care . The massage intervention produced immediate relaxation and pain relief effects . A power analysis based on trends in the longer-term effects indicate that a study with 80 subjects per group is likely to detect statistically significant effects of usual hospice care with twice-weekly massage therapy sessions on pain intensity , analgesic dosages , and quality of life . Lessons we learned from conducting this pilot study are being used to improve documentation of our hospice program outcomes and to plan a definitive study . [ Article copies available for a fee from The Haworth Document Delivery Service : 1 - 800 - 342 - 9678 . E-mail address : [email protected] The use of complementary therapies , such as massage and aromatherapy massage , is rising in popularity among patients and healthcare professionals . They are increasingly being used to improve the quality of life of patients , but there is little evidence of their efficacy . This study assessed the effects of massage and aromatherapy massage on cancer patients in a palliative care setting . We studied 103 patients , who were r and omly allocated to receive massage using a carrier oil ( massage ) or massage using a carrier oil plus the Roman chamomile essential oil ( aromatherapy massage ) . Outcome measurements included the Rotterdam Symptom Checklist ( RSCL ) , the State – Trait Anxiety Inventory ( STAI ) and a semi-structured question naire , administered 2 weeks postmassage , to explore patients ' perceptions of massage . There was a statistically significant reduction in anxiety after each massage on the STAI ( P < 0.001 ) , and improved scores on the RSCL : psychological ( P < 0.001 ) , quality of life ( P < 0.01 ) , severe physical ( P < 0.05 ) , and severe psychological ( P < 0.05 ) subscales for the combined aromatherapy and massage group . The aromatherapy group 's scores improved on all RSCL subscales at the 1 % level of significance or better , except for severely restricted activities . The massage group 's scores improved on four RSCL subscales but these improvements did not reach statistical significance . Massage with or without essential oils appears to reduce levels of anxiety . The addition of an essential oil seems to enhance the effect of massage and to improve physical and psychological symptoms , as well as overall quality of life This trial compared pain , quality of life , and analgesic use in a sample of patients with cancer pain ( n=24 ) who received either st and ard opioid management plus rest ( Arm A ) or st and ard opioid management plus Reiki ( Arm B ) . Participants either rested for 1.5 hr on Days 1 and 4 or received two Reiki treatments ( Days 1 and 4 ) one hour after their first afternoon analgesic dose . Visual analogue scale ( VAS ) pain ratings , blood pressure , heart rate , and respirations were obtained before and after each treatment/rest period . Analgesic use and VAS pain scores were reported for 7 days . Quality of life was assessed on Days 1 and 7 . Participants in Arm B experienced improved pain control on Days 1 and 4 following treatment , compared to Arm A , and improved quality of life , but no overall reduction in opioid use . Future research will determine the extent to which the benefits attributed to Reiki in this study may have been due to touch OBJECTIVES The objective of this study was to determine the effects of physical therapy , including massage and exercise , on pain and mood in patients with advanced terminal cancer . DESIGN The design was a r and omized controlled pilot study . SUBJECTS Twenty-four ( 24 ) patients with terminal cancer were r and omly assigned to one of two treatment groups . INTERVENTIONS Group A received a physiotherapy intervention consisting of several massage techniques , mobilizations , and local and global exercises . Group B received a simple h and contact/touch to areas of pain ( cervical area , shoulder , interscapular area , heels , and gastrocnemius ) , which was maintained for the same period of time as the intervention group . All patients received six sessions of 30 - 35 minutes in duration over a 2-week period . OUTCOMES Outcomes were collected at baseline , at 1 week , and at a 2-week follow-up ( after treatment completion ) by an assessor blinded to the treatment allocation of the participants . Outcomes included the Brief Pain Inventory ( BPI , 0 - 10 scale ) , Memorial Pain Assessment Card ( 0 - 10 scale ) , and Memorial Symptom Assessment Scale ( MSAS Physical , Psychological , 0 - 4 scale ) . Baseline between-group differences were assessed with an independent t-test . A two-way repeated- measures analysis of variance was used to examine the effects of the intervention . RESULTS There were no significant between-group baseline differences ( p>0.2 ) . A significant group × time interaction with greater improvements in group A was found for BPI worst pain ( F=3.5 , p=0.036 ) , BPI pain right now ( F=3.94 , p=0.027 ) , and BPI index ( F=13.2 , p<0.001 ) , for MSAS Psychological ( F=8.480 , p=0.001 ) . CONCLUSIONS The combination of massage and exercises can reduce pain and improve mood in patients with terminal cancer . A sustained effect on pain and psychologic distress existed ; however , parameters such as physical distress and the least pain were no greater in the intervention group as compared to the sham |
12,965 | 30,458,634 | There are low- to very-low- quality evidence that some interventions ( use of cervical collars after non-plated anterior cervical diskectomy an fusion , structured physiotherapy , and interactive patients ’ education ) provide some benefit within functioning , pain , and selected psychological variables in patients undergoing cervical disk surgery .
Conclusion : There is insufficient evidence with few trials of low quality to allow any conclusion to be drawn about the effectiveness , harms , and general ineffectiveness of rehabilitation for people who have had cervical disk surgery for pain or radiculopathy | Objectives : To present a synopsis of evidence on the efficacy of rehabilitation after cervical disk surgery performed for neck pain and radiculopathy . | Background Many patients with cervical disc disease require leave from work , due to long-lasting , complex symptoms , including chronic pain and reduced levels of physical and psychological function . Surgery on a few segmental levels might be expected to resolve disc-specific pain and reduce neurological deficits , but not the non-specific neck pain and the frequent illness . No study has investigated whether post-surgery physiotherapy might improve the outcome of surgery . The main purpose of this study was to evaluate whether a well-structured rehabilitation programme might add benefit to the customary post-surgical treatment for cervical disc disease , with respect to function , disability , work capability , and cost effectiveness . Methods / Design This study was design ed as a prospect i ve , r and omised , controlled , multi-centre study . An independent , blinded investigator will compare two alternatives of rehabilitation . We will include 200 patients of working age , with cervical disc disease confirmed by clinical findings and symptoms of cervical nerve root compression . After providing informed consent , study participants will be r and omised to one of two alternative physiotherapy regimes ; ( A ) customary treatment ( information and advice on a specialist clinic ) ; or ( B ) customary treatment plus active physiotherapy . Physiotherapy will follow a st and ardised , structured programme of neck-specific exercises combined with a behavioural approach . All patients will be evaluated both clinical ly and subjectively ( with question naires ) before surgery and at 6 weeks , 3 months , 6 months , 12 months , and 24 months after surgery . The main outcome variable will be neck-specific disability . Cost-effectiveness will also be calculated . Discussion We anticipate that the results of this study will provide evidence to support physiotherapeutic rehabilitation applied after surgery for cervical radiculopathy due to cervical disc disease . Trial registration Clinical Trials.gov identifier : Study Design : Retrospective review of the prospect i ve American College of Surgeons National Surgical Quality Improvement Project ( ACS NSQIP ) data base with 30-day follow-up of 2164 patients undergoing elective anterior cervical discectomy and fusion ( ACDF ) . Objective : To determine factors independently associated with increased length of stay ( LOS ) and complications after ACDF to facilitate preoperative planning and setting of realistic expectations for patients and providers . Summary of Background Data : The effect of individual preoperative factors on LOS and complications has been evaluated in small-scale studies . Large data base analysis with multivariate analysis of these variables has not been reported . Methods : The ACS NSQIP data base from 2005 to 2010 was queried for patients undergoing ACDF procedures . Preoperative and perioperative variables were collected . Multivariate regression determined significant predictors ( P<0.05 ) of extended LOS and complications . Results : Average LOS was 2.0±4.0 days ( mean±SD ) with a range of 0–103 days . By multivariate analysis , age 65 years and above , functional status , transfer from facility , preoperative anemia , and diabetes were the preoperative factors predictive of extended LOS . Major complications , minor complications , and extended surgery time were the perioperative factors associated with increased LOS . The elongating effect of these variables was determined , and ranged from 0.5 to 5.0 days . Seventy-one patients ( 3.3 % ) had a total of 92 major complications , including return to operating room ( 40 ) , venous thrombotic events ( 13 ) , respiratory ( 21 ) , cardiac ( 6 ) , mortality ( 5 ) , sepsis ( 4 ) , and organ space infection ( 3 ) . Multivariate analysis determined ASA score ≥3 , preoperative anemia , age 65 years and above , extended surgery time , and male sex to be predictive of major complications ( odds ratios ranging between 1.756 and 2.609 ) . No association was found between levels fused and LOS or complications . Conclusion : Extended LOS after ACDF is associated with factors including age , anemia , and diabetes , as well as the development of postoperative complications . One in 33 patients develops a major complication postoperatively , which are associated with an increased LOS of 5 days Objectives The aims of this study are to answer the following questions ( 1 ) How does the pain intensity of lumbar and cervical disc surgery patients change within a postoperative time frame of 5 years ? ( 2 ) Which sociodemographic , medical , work-related , and psychological factors are associated with postoperative pain in lumbar and cervical disc surgery patients ? Methods The baseline survey ( T0 ; n = 534 ) was conducted 3.6 days ( SD 2.48 ) post-surgery in the form of face-to-face interviews . The follow-up interviews were conducted 3 months ( T1 ; n = 486 patients ) , 9 months ( T2 ; n = 457 ) , 15 months ( T3 ; n = 438 ) , and 5 years ( T4 ; n = 404 ) post-surgery . Pain intensity was measured on a numeric rating-scale ( NRS 0–100 ) . Estimated changes to and influences on postoperative pain by r and om effects were accounted by regression models . Results Average pain decreased continuously over time in patients with lumbar herniated disc ( Wald Chi² = 25.97 , p<0.001 ) . In patients with cervical herniated disc a reduction of pain was observed , albeit not significant ( Chi² = 7.02 , p = 0.135 ) . Two predictors were associated with postoperative pain in lumbar and cervical disc surgery patients : the subjective prognosis of gainful employment ( p<0.001 ) and depression ( p<0.001 ) . Conclusion In the majority of disc surgery patients , a long-term reduction of pain was observed . Cervical surgery patients seemed to benefit less from surgery than the lumbar surgery patients . A negative subjective prognosis of gainful employment and stronger depressive symptoms were associated with postoperative pain . The findings may promote multimodal rehabilitation concepts including psychological and work-related support Study Design . Population ‐based , cross‐sectional mailed survey . Objective . To determine the lifetime , period , and point prevalence of neck pain and its related disability among Saskatchewan adults and investigate the presence and strength of nonresponse bias . Summary of Background Data . In Europe , the life‐time and point prevalence of neck pain is almost as high as the prevalence of low back pain . Similarly , chronic neck pain is highly prevalent and a common source of disability in the working‐age population . However , no studies specifically have documented the prevalence of neck pain and its related disability in North America . Methods . The Saskatchewan Health and Back Pain Survey was mailed to 2184 r and omly selected Saskatchewan adults aged 20‐69 years . Fifty‐five percent of the study population participated . The presence of nonresponse bias was investigated through logistic regression and wave analysis . The Chronic Pain Question naire was used to classify the severity of chronic neck pain . Results . The age‐st and ardized lifetime prevalence of neck pain is 66.7 % ( 95 % confidence interval , 63.8‐69.5 ) , and the point prevalence is 22.2 % ( 95 % confidence interval , 19.7‐24.7 ) . The age‐st and ardized 6‐month prevalence of low‐intensity and low‐disability neck pain is 39.7 % ( 95 % confidence interval , 36.7‐42.7 ) , whereas it is 10.1 % ( 95 % confidence interval , 8.2‐11.9 ) for high‐intensity and low‐disability neck pain and 4.6 % ( 95 % confidence interval , 3.3‐5.8 ) for significantly disabling neck pain . The prevalence of low‐intensity and low‐disability neck pain decreases with age . More women experience high‐disability neck pain than men . Wave analysis suggests that the point prevalence and 6‐month prevalence of high‐intensity and low‐disability neck pain are overestimated in this survey . Conclusion . This cross‐sectional study shows that neck pain is highly prevalent in Saskatchewan and that it significantly disables 4.6 % ( 95 % confidence interval , 3.3‐5.8 ) of the adult population Study Design . Prospect i ve cohort study . Objective . To examine differences between preoperative and postoperative fear of movement and investigate the relationship between fear of movement and pain , disability and physical health after spinal surgery for degenerative conditions . Summary of Background Data . Consistent evidence supports the relationship between fear of movement and higher levels of pain and disability in various chronic pain population s. Fear of movement among patients undergoing spinal surgery for chronic pain has received little attention in the literature . Methods . Participants were 141 patients treated with surgery for lumbar and cervical degenerative conditions . Assessment s were conducted before surgery and 6 weeks and 3 months after hospitalization . Fear of movement was measured with the Tampa Scale for Kinesiophobia and outcomes were measured with the Brief Pain Inventory , Oswestry or Neck Disability Index , and 12-Item Short Form Health Survey ( SF-12 ) . Results . Follow-up rates were 91 % and 87 % for 6 weeks and 3 months , respectively . Fear of movement beliefs improved after surgery , but 49 % of patients continued to have high fear of movement at 6-week follow-up and 39 % at 3-month follow-up . Patients with higher levels of fear of movement had poorer postoperative outcomes . Multilevel linear regression analyses found that postoperative fear of movement was independently associated with postoperative pain intensity , pain interference , disability , and physical health ( P < 0.001 ) , after controlling for depression , age , sex , education , race , comorbidities , type and area of surgery , prior surgeries , and baseline outcome score . Preoperative fear of movement was not predictive of poorer surgical outcomes . Conclusion . Results demonstrate that postoperative but not preoperative fear of movement beliefs explain unique and significant variance in postoperative pain , disability , and physical health . Clinicians interested in improving surgical outcomes should address postoperative fear of movement along with other traditional clinical and medical risk factors . Recommendations include postoperative screening for high fear of movement beliefs and incorporating cognitive-behavioral techniques into postoperative rehabilitation for at-risk surgical spine patients BACKGROUND CONTEXT Spinal surgery in the workers compensation population shows evidence of less favorable outcomes than in general health cases . Although spine surgery has been alleged to be a cause of poor outcomes , such outcomes may be improved by appropriate postsurgical rehabilitation . PURPOSE To compare objective demographic , physical and psychological measurements and socioeconomic outcomes of treatment in work-related disabling cervical pain for the combination of anterior cervical fusion ( ACF ) plus functional restoration , compared with rehabilitation alone . STUDY DESIGN / SETTING A prospect i ve study of patients undergoing ACF for degenerative disc disease before rehabilitation for work-related musculoskeletal disorders versus neck pain unoperated controls , with data collected in an outpatient tertiary interdisciplinary rehabilitation setting . PATIENT SAMPLE A group of 52 patients completed a functional restoration treatment program after undergoing ACF ( Group S ) at one or two levels for degenerative cervical disc disease . During the study period , 625 patients with work-related neck pain were identified from the same study population , from which a rehabilitation ( Group R ) comparison group ( n=150 ) was identified who were stratified according to the number and location of other compensable body parts . OUTCOME MEASURES Socioeconomic outcomes relevant to chronic disabling work-related cervical spinal disorders are reported based on 1-year posttreatment interviews . Pre- to posttreatment assessment of pain intensity , disability , depression and cumulative physical capability were assessed prospect ively . METHODS All patients were totally or partially disabled before completing an intensive , medically supervised , functional restoration program combining quantitatively directed exercise progression with a multimodal disability management approach . Preprogram preparation included drug detoxification , psychotropic medication management and preparatory aerobic and mobility training . The intensive treatment phase involved strength and endurance training , with counseling geared to goals of work return and fitness maintenance . The 1-year structured clinical interview had a contact rate of 93 % to 95 % , and partial information acquisition on all patients . RESULTS Although Group S had lower work return and work retention outcomes , the differences were not significant . Group S patients had significantly more health utilization from a new provider in the year after completion of functional restoration ( 46 % vs 24 % ; OR=2.7 [ 1.3 , 5.3 ] , p<.004 ) . Group S patients were also more likely to be depressed , both at pre- and postrehabilitation . There were no significant differences in recurrent injury , additional surgery , physical measures or pain/disability self-report between the groups . CONCLUSIONS Workers compensation patients with chronic disabling work-related cervical spinal disorders who undergo a cervical fusion , combined with functional restoration , have socioeconomic outcomes after their surgery statistically similar to those for unoperated controls . Surgery patients had a higher rate of additional health-care-seeking behaviors from new providers and a greater likelihood of being clinical ly depressed before and after rehabilitation . This study suggests that cervical fusion for degenerative disc disease in workers compensation patients is not contraindicated , as long as interdisciplinary rehabilitation is available for complex cases after the surgical procedure Cervical total disk arthroplasty has proven to be an effective and safe alternative for anterior cervical diskectomy and fusion ( ACDF ) for the treatment of cervical disk degenerative disease . However , whether and when cervical disk arthroplasty is indicated for preoperative cervical spine kyphosis is unclear . In the authors ' clinical experiences , preoperative kyphosis can generally be divided into reducible and irreducible forms according to the results of dynamic flexion-extension lateral radiographs . Reducible kyphosis is mostly related to local disk prolapse , clinical symptoms , and musculature weakness , but irreducible kyphosis is always associated with significant cervical degeneration or congenital bone malformation . In this study , 32 patients with preoperative reducible kyphosis were r and omized in a 1:1 ratio to either single-level total cervical arthroplasty with the Discover cervical disk prosthesis ( DePuy Spine , Raynham , Massachusetts ) ( arthroplasty group ) or single-level ACDF with a polyetheretherketone cage and plate ( ACDF group ) . No significant differences existed in clinical and radiological results at 2-year follow-up between the arthroplasty and ACDF groups . The global and functional spinal unit angles of the arthroplasty group were significantly lower than those of the ACDF group 6 months postoperatively , which was consistent with the result of the comparison in Neck Disability Index score . However , the sagittal alignment of the overall cervical spine and the treated segment and the Neck Disability Index score significantly improved after 6 months in the arthroplasty group but not in the ACDF group . Therefore , preoperative reducible kyphosis is not a contraindication for cervical total disk arthroplasty . However , neck strength-building exercises should be emphasized for the postoperative rehabilitation after cervical total disk arthroplasty Anterior cervical discectomy and fusion ( ACDF ) is a common surgical intervention for radiculopathy result ing from degenerative cervical spine conditions . Post-surgical cervical collar use is believed to reduce post-operative pain , provide the patient with a sense of security during activities of daily living and even reduce rates of non-fusion . This prospect i ve r and omized controlled pilot trial investigates trial design feasibility in relation to prospect i ve physical , functional , and quality of life-related outcomes of patients undergoing ACDF with interbody cage , with ( n = 17 ) and without ( n = 16 ) post-operative cervical collar usage . Results show that the sample provides sufficient statistical power to show that the use of a rigid cervical collar during 6 post-operative weeks is associated with significantly lower levels of neck disability index after 6 weeks and significantly lower levels of prospect i ve neck pain . To investigate causal quality of life or fusion rate outcomes , sample size needs to be increased at least fourfold and optimally sixfold when accounting for data loss in prospect i ve follow-up . The study suggests that post-surgical cervical collar usage may help certain patients cope with initial post-operative pain and disability OBJECTIVE Structured physiotherapy has been suggested as treatment before as well as after surgery to improve clinical outcomes in patients with cervical radiculopathy ( CR ) , but r and omized clinical trials to inform evidence -based clinical guidelines for the treatment of patients with CR after surgery are lacking . The aim of this study was to compare the results of structured postoperative physiotherapy combining neck-specific exercises with a behavioral approach to a st and ard postoperative approach in patients who had undergone surgery for cervical disc disease with CR at 6 months after surgery . METHODS Patients with cervical disc disease and persistent CR who were scheduled for surgery were r and omized preoperatively to structured postoperative physiotherapy ( n = 101 ) or a st and ard postoperative approach ( n = 100 ) . The latter included pragmatic physiotherapy in accordance with the usual Swedish postoperative care . Outcome measures included patient-reported neck disability as measured with the Neck Disability Index ( NDI ) , intensity and frequency of neck and arm pain , global outcome of treatment , and expectation fulfillment , as well as enablement . RESULTS Patients who received structured postoperative physiotherapy reported greater expectation fulfillment ( p = 0.01 ) , and those who attended at least 50 % of the treatment sessions reported less neck pain frequency ( p = 0.05 ) , greater expectation fulfillment ( p = 0.001 ) , and greater enablement ( p = 0.04 ) compared with patients who received the st and ard postoperative approach . No other difference between treatment groups was found ( p > 0.15 ) . The NDI and neck and arm pain intensity were improved in both groups at 6 months after surgery ( p < 0.001 ) . Additional use of postoperative physiotherapy was reported by 61 % of the patients who received the st and ard postoperative approach . CONCLUSIONS The results from this first r and omized clinical trial of postoperative physiotherapy showed only minor additional benefit of structured postoperative physiotherapy compared with st and ard postoperative approach 6 months postoperatively in patients who underwent surgery for cervical disc disease with CR . Patients who received structured postoperative physiotherapy reported higher expectation fulfillment , and many patients in the st and ard postoperative approach group perceived a need for additional treatments after surgery , suggesting that patients with CR are in need of further postoperative support . The results confirm that neck-specific exercises are tolerated postoperatively by patients with CR , but more studies of postoperative physiotherapy are needed to inform clinical guidelines for this patient group . Clinical trial registration no. : NCT01547611 ( clinical trials.gov ) Study Design . Prospect i ve r and omized controlled trial . Objective . To study the outcome of anterior cervical decompression and fusion combined with a structured physiotherapy program compared with the same physiotherapy program alone for patients with cervical radiculopathy . Summary of Background Data . Knowledge concerning the effects of interventions for patients with cervical radiculopathy is scarce due to a lack of r and omized studies . Methods . Sixty-three patients were r and omized to surgery with postoperative physiotherapy ( n = 31 ) or physiotherapy alone ( n = 32 ) . The surgical group was treated with anterior cervical decompression and fusion . The physiotherapy program included general/specific exercises and pain-coping strategies . The outcome measures were disability ( Neck Disability Index ) , neck and arm pain intensity ( visual analogue scale ) , and the patient 's global assessment . Patients were followed for 24 months . Results . The result from the repeated- measures analysis of variance showed no significant between-group difference for Neck Disability Index ( P = 0.23 ) . For neck pain intensity , the repeated- measures analysis of variance showed a significant between-group difference during the study period in favor of the surgical group ( P = 0.039 ) . For arm pain intensity , no significant between-group differences were found according to the repeated- measures analysis of variance ( P = 0.580 ) . Eighty-seven percent of the patients in the surgical group rated their symptoms as “ better/much better ” at the 12-month follow-up compared with 62 % in the nonsurgical group ( P < 0.05 ) . At 24 months , the corresponding figures were 81 % and 69 % ( P = 0.28 ) . The difference was significant only at the 12-month follow-up in favor of the surgical group . Significant reduction in Neck Disability Index , neck pain , and arm pain compared with baseline was seen in both groups ( P < 0.001 ) . Conclusion . In this prospect i ve , r and omized study of patients with cervical radiculopathy , it was shown that surgery with physiotherapy result ed in a more rapid improvement during the first postoperative year , with significantly greater improvement in neck pain and the patient 's global assessment than physiotherapy alone , but the differences between the groups decreased after 2 years . Structured physiotherapy should be tried before surgery is chosen . Level of Evidence : Objective The purpose of this study was to compare postoperative rehabilitation with structured physiotherapy to the st and ard approach in patients with cervical radiculopathy ( CR ) in a prospect i ve r and omized study at 6 months follow‐up based on measures of neck‐related physical function , self‐efficacy , and coping strategies . Methods Patients with persistent CR and scheduled for surgery ( N = 202 ) were r and omly assigned to structured postoperative physiotherapy or a st and ard postoperative approach . Structured postoperative physiotherapy combined neck‐specific exercises with a behavioral approach . Baseline , 3‐month , and 6‐month evaluations included question naires and clinical examinations . Neck muscle endurance , active cervical range of motion , self‐efficacy , pain catastrophizing ( CSQ‐CAT ) , perceived control over pain , and ability to decrease pain were analyzed for between‐group differences using complete case and per‐ protocol approaches . Results No between‐group difference was reported at the 6‐month follow‐up ( P = .05‐.99 ) , but all outcomes had improved from baseline ( P < .001 ) . Patients undergoing structured postoperative physiotherapy with ≥50 % attendance at treatment sessions had larger improvements in CSQ‐CAT ( P = .04 ) during the rehabilitation period from 3 to 6 months after surgery compared with the patients who received st and ard postoperative approach . Conclusions No between‐group difference was found at 6 months after surgery based on measures of neck‐related physical function , self‐efficacy , and coping strategies . However , the results confirm that neck‐specific exercises are tolerated by patients with CR after surgery and may suggest a benefit from combining surgery with structured postoperative physiotherapy for patients with CR |
12,966 | 28,220,472 | AUTHORS ' CONCLUSIONS In patients with resistant hypertension , there is low quality evidence that renal denervation does not change major cardiovascular events , and renal function .
There was moderate quality evidence that it does not change blood pressure and and low quality evidence that it caused an increaseof bradycardia episodes . | BACKGROUND Resistant hypertension is highly prevalent among the general hypertensive population and the clinical management of this condition remains problematic .
Different approaches , including a more intensified antihypertensive therapy , lifestyle modifications , or both , have largely failed to improve patients ' outcomes and to reduce cardiovascular and renal risk .
As renal sympathetic hyperactivity is a major driver of resistant hypertension , renal sympathetic ablation ( renal denervation ) has been recently proposed as a possible therapeutic alternative to treat this condition .
OBJECTIVES We sought to evaluate the short- and long-term effects of renal denervation in individuals with resistant hypertension on clinical end points , including fatal and non-fatal cardiovascular events , all-cause mortality , hospital admissions , quality of life , blood pressure control , left ventricular hypertrophy , cardiovascular and metabolic profile , and kidney function , as well as the potential adverse events related to the procedure . | Renal denervation reduces office blood pressure in patients with resistant hypertension . This study investigated the effects of renal denervation on blood pressure , heart rate , and chronotropic index at rest , during exercise , and at recovery in 60 patients ( renal denervation group=50 , control group=10 ) with resistant hypertension using a st and ardized bicycle exercise test protocol performed 6 and 12 months after renal denervation . After renal denervation , exercise blood pressure at rest was reduced from 158±3/90±2 to 141±3/84±4 mm Hg ( P<0.001 for systolic blood pressure/P=0.007 for diastolic blood pressure ) after 6 months and 139±3/83±4 mm Hg ( P<0.001/P=0.022 ) after 12 months . Exercise blood pressure tended to be lower at all stages of exercise at 6- and 12-month follow-up in patients undergoing renal denervation , although reaching statistical significance only at mild-to-moderate exercise levels ( 75–100 W ) . At recovery after 1 minute , blood pressure decreased from 201±4/95±2 to 177±4/88±2 ( P<0.001/P=0.066 ) and 188±6/86±2 mm Hg ( P=0.059/P=0.01 ) after 6 and 12 months , respectively . Heart rate was reduced after renal denervation from 71±3 bpm at rest , 128±5 bpm at maximum workload , and 96±5 bpm at recovery after 1 minute to 66±2 ( P<0.001 ) , 115±5 ( P=0.107 ) , and 89±3 bpm ( P=0.008 ) after 6 months and to 69±3 ( P=0.092 ) , 122±7 ( P=0.01 ) , and 93±4 bpm ( P=0.032 ) after 12 months . Mean exercise time increased from 6.59±0.33 to 8.4±0.32 ( P<0.001 ) and 9.0±0.41 minutes ( P=0.008 ) , and mean workload increased from 93±2 to 100±2 ( P<0.001 ) and 101±3 W ( P=0.007 ) at 6- and 12-month follow-up , respectively . No changes were observed in the control group . In conclusion , renal denervation reduced blood pressure and heart rate during exercise , improved mean workload , and increased exercise time without impairing chronotropic competence BACKGROUND The potential role of renal denervation ( RD ) in patients with AF and less severe hypertension is unknown . OBJECTIVE The purpose of this study was to assess the potential role of RD as an adjunct to pulmonary vein isolation ( PVI ) in patients with atrial fibrillation ( AF ) and moderate resistant or severe resistant hypertension . METHODS The data for this study were obtained from 2 different prospect i ve r and omized studies , analyzed by meta- analysis . Patients with paroxysmal AF or persistent AF and moderate resistant hypertension ( office blood pressure BP ≥140/90 mm Hg and < 160/100 mm Hg ; first study ; n = 48 ) or severe resistant hypertension ( ≥160/100 mm Hg ; second study ; n = 38 ) were r and omized to PVI or PVI with RD . RESULTS At 12 months , 26 of the 41 PVI with RD patients ( 63 % ) were AF-free vs 16 of the 39 patients ( 41 % ) in the PVI-only group ( P = .014 ) . In patients with severe hypertension , 11 of the 18 PVI with RD patients ( 61 % ) vs 5 of the 18 PVI-only patients ( 28 % ) were AF-free ( P = .03 ) . For moderate hypertension , the differences were less dramatic : 11 of 21 ( 52 % ) vs 15 of 23 ( 65 % ) when RD added ( P = .19 ) . The superior efficacy of adding RD was most apparent in persistent AF and severe hypertension ( hazard ratio 0.25 , confidence interval 0.09 - 0.72 , P = .01 ) . Duration of the procedure and fluoroscopy were nonsignificantly longer in the RD group . CONCLUSION RD may improve the results of PVI in patients with persistent AF and /or severe resistant hypertension & NA ; We aim ed to investigate for the first time the blood pressure (BP)–lowering effect of renal sympathetic denervation ( RDN ) versus clinical ly adjusted drug treatment in true treatment-resistant hypertension ( TRH ) after excluding patients with confounding poor drug adherence . Patients with apparent TRH ( n=65 ) were referred for RDN , and those with secondary and spurious hypertension ( n=26 ) were excluded . TRH was defined as office systolic BP ( SBP ) > 140 mm Hg , despite maximally tolerated doses of ≥3 antihypertensive drugs including a diuretic . In addition , ambulatory daytime SBP > 135 mm Hg after witnessed intake of antihypertensive drugs was required , after which 20 patients had normalized BP and were excluded . Patients with true TRH were r and omized and underwent RDN ( n=9 ) performed with Symplicity Catheter System versus clinical ly adjusted drug treatment ( n=10 ) . The study was stopped early for ethical reasons because RDN had uncertain BP-lowering effect . Office SBP and diastolic BP in the drug-adjusted group changed from 160±14/88±13 mm Hg ( ±SD ) at baseline to 132±10/77±8 mm Hg at 6 months ( P<0.0005 and P=0.02 , SBP and diastolic BP , respectively ) and in the RDN group from 156±13/91±15 to 148±7/89±8 mm Hg ( P=0.42 and P=0.48 , SBP and diastolic BP , respectively ) . SBP and diastolic BP were significantly lower in the drug-adjusted group at 6 months ( P=0.002 and P=0.004 , respectively ) , and absolute changes in SBP were larger in the drug-adjusted group ( P=0.008 ) . Ambulatory BPs changed in parallel to office BPs . Our data suggest that adjusted drug treatment has superior BP lowering effects compared with RDN in patients with true TRH . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : The first studies on renal denervation ( RDN ) suggest that this treatment is feasible , effective , and safe in the short term . Presently available data are promising , but important uncertainties exist ; therefore , SYMPATHY has been initiated . SYMPATHY is a multicenter , r and omized , controlled trial in patients r and omized to RDN in addition to usual care ( intervention group ) or to continued usual care ( control group ) . R and omization will take place in a ratio of 2 to 1 . At least 300 participants will be included to answer the primary objective . Sample size may be extended to a maximum of 570 to address key secondary objectives . The primary objective is to assess whether RDN added to usual care compared with usual care alone reduces blood pressure ( BP ) ( ambulatory daytime systolic BP ) in subjects with an average daytime systolic BP ≥135 , despite use of ≥3 BP-lowering agents , 6 months after RDN . Key secondary objectives are evaluated at 6 months and at regular intervals during continued follow-up and include the effect of RDN on the use of BP-lowering agents , in different subgroups ( across strata of estimated glomerular filtration rate and of baseline BP ) , on office BP , quality of life , and cost-effectiveness Percutaneous renal sympathetic denervation by radiofrequency energy has been reported to reduce blood pressure ( BP ) by the reduction of renal sympathetic efferent and afferent signaling . We evaluated the effects of this procedure on BP and sleep apnea severity in patients with resistant hypertension and sleep apnea . We studied 10 patients with refractory hypertension and sleep apnea ( 7 men and 3 women ; median age : 49.5 years ) who underwent renal denervation and completed 3-month and 6-month follow-up evaluations , including polysomnography and selected blood chemistries , and BP measurements . Antihypertensive regimens were not changed during the 6 months of follow-up . Three and 6 months after the denervation , decreases in office systolic and diastolic BPs were observed ( median : −34/−13 mm Hg for systolic and diastolic BPs at 6 months ; both P<0.01 ) . Significant decreases were also observed in plasma glucose concentration 2 hours after glucose administration ( median : 7.0 versus 6.4 mmol/L ; P=0.05 ) and in hemoglobin A1C level ( median : 6.1 % versus 5.6 % ; P<0.05 ) at 6 months , as well as a decrease in apnea-hypopnea index at 6 months after renal denervation ( median : 16.3 versus 4.5 events per hour ; P=0.059 ) . In conclusion , catheter-based renal sympathetic denervation lowered BP in patients with refractory hypertension and obstructive sleep apnea , which was accompanied by improvement of sleep apnea severity . Interestingly , there are also accompanying improvements in glucose tolerance . Renal sympathetic denervation may conceivably be a potentially useful option for patients with comorbid refractory hypertension , glucose intolerance , and obstructive sleep apnea , although further studies are needed to confirm these proof-of-concept data BACKGROUND Prior unblinded studies have suggested that catheter-based renal-artery denervation reduces blood pressure in patients with resistant hypertension . METHODS We design ed a prospect i ve , single-blind , r and omized , sham-controlled trial . Patients with severe resistant hypertension were r and omly assigned in a 2:1 ratio to undergo renal denervation or a sham procedure . Before r and omization , patients were receiving a stable antihypertensive regimen involving maximally tolerated doses of at least three drugs , including a diuretic . The primary efficacy end point was the change in office systolic blood pressure at 6 months ; a secondary efficacy end point was the change in mean 24-hour ambulatory systolic blood pressure . The primary safety end point was a composite of death , end-stage renal disease , embolic events result ing in end-organ damage , renovascular complications , or hypertensive crisis at 1 month or new renal-artery stenosis of more than 70 % at 6 months . RESULTS A total of 535 patients underwent r and omization . The mean ( ±SD ) change in systolic blood pressure at 6 months was -14.13±23.93 mm Hg in the denervation group as compared with -11.74±25.94 mm Hg in the sham-procedure group ( P<0.001 for both comparisons of the change from baseline ) , for a difference of -2.39 mm Hg ( 95 % confidence interval [ CI ] , -6.89 to 2.12 ; P=0.26 for superiority with a margin of 5 mm Hg ) . The change in 24-hour ambulatory systolic blood pressure was -6.75±15.11 mm Hg in the denervation group and -4.79±17.25 mm Hg in the sham-procedure group , for a difference of -1.96 mm Hg ( 95 % CI , -4.97 to 1.06 ; P=0.98 for superiority with a margin of 2 mm Hg ) . There were no significant differences in safety between the two groups . CONCLUSIONS This blinded trial did not show a significant reduction of systolic blood pressure in patients with resistant hypertension 6 months after renal-artery denervation as compared with a sham control . ( Funded by Medtronic ; SYMPLICITY HTN-3 Clinical Trials.gov number , NCT01418261 . ) Objective : Renal denervation ( RDN ) has been demonstrated to reduce muscle sympathetic nerve activity ( MSNA ) and blood pressure ( BP ) in patients with resistant hypertension . Whether alterations of arterial stiffness may contribute to BP-lowering effects of RDN is unknown . Methods : We measured office BP and arterial stiffness using fingertip tonometry-derived augmentation index ( EndoPAT2000 ) at baseline and at 3-month follow-up in 50 consecutive patients with resistant hypertension . Forty patients received RDN and 10 patients served as controls . MSNA was obtained in 20 RDN and 10 non-RDN patients . Results : Baseline BP averaged 170/92 ± 19/15 mmHg ( RDN ) and 171/93 ± 14/8 mmHg ( non-RDN ) despite the use of 4.9 ± 1.9 and 4.4 ± 2.0 antihypertensive drugs , respectively . RDN significantly reduced SBP ( 170 ± 19 vs. 154 ± 25 mmHg ; P < 0.001 ) and DBP ( 92 ± 15 vs. 84 ± 16 mmHg ; P < 0.001 ) , augmentation index ( 30.6 ± 23.8 vs. 22.7 ± 22.4 % ; P = 0.002 ) , AI@75 corrected for heart rate ( 22.4 ± 21.6 vs. 14.4 ± 20.7 ; P = 0.002 ) and MSNA ( 80 ± 15 vs. 71 ± 18 bursts/100 heartbeats ; P < 0.01 ) . Changes in AI@75 with RDN were unrelated to SBP ( r = 0.043 ; P = 0.79 ) , and DBP ( r = 0.092 ; P = 0.57 ) and MSNA changes ( r = −0.17 ; P = 0.49 ) . No changes in BP , augmentation index , AI@75 or MSNA were observed in the non-RDN group . Conclusion : RDN results in a substantial and rapid reduction in augmentation index , which appears to be independent of BP and MSNA changes . These findings are indicative of a beneficial effect of RDN on arterial stiffness in patients with resistant hypertension and may contribute to the sustained BP-lowering effect of RDN Few data are available with regard to the effectiveness of renal sympathetic denervation in patients with resistant hypertension yet only mildly elevated blood pressure ( BP ) . Patients with resistant hypertension and slightly elevated BP ( day-time systolic pressure , 135–149 and diastolic pressure , 90–94 mm Hg on 24-hour ambulatory measurement ) were r and omized in a 1:1 ratio to renal sympathetic denervation with the Symplicity Flex Catheter ( Medtronic ) or an invasive sham procedure . The primary efficacy end point was the change in 24-hour systolic BP at 6 months between groups in the intention to treat population . A total of 71 patients underwent r and omization . Baseline day-time systolic BP was 144.4±4.8 mm Hg in patients assigned to denervation and 143.0±4.7 mm Hg in patients r and omized to the sham procedure . The mean change in 24-hour systolic BP in the intention to treat cohort at 6 months was −7.0 mm Hg ( 95 % confidence interval , −10.8 to −3.2 ) for patients undergoing denervation and −3.5 mm Hg ( 95 % confidence interval , −6.7 to −0.2 ) in the sham group ( P=0.15 ) . In the per protocol population , the change in 24-hour systolic BP at 6 months was −8.3 mm Hg ( 95 % confidence interval , −11.7 to −5.0 ) for patients undergoing denervation and −3.5 mm Hg ( 95 % confidence interval , −6.8 to −0.2 ) in the sham group ( P=0.042 ) . In patients with mild resistant hypertension , renal sympathetic denervation failed to show a significant reduction in the primary end point of 24-hour systolic BP at 6 months between groups in the intention to treat analysis . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01656096 OBJECTIVES The aim of this prospect i ve r and omized study was to assess the impact of renal artery denervation in patients with a history of refractory atrial fibrillation ( AF ) and drug-resistant hypertension who were referred for pulmonary vein isolation ( PVI ) . BACKGROUND Hypertension is the most common cardiovascular condition responsible for the development and maintenance of AF . Treating drug-resistant hypertension with renal denervation has been reported to control blood pressure , but any effect on AF is unknown . METHODS Patients with a history of symptomatic paroxysmal or persistent AF refractory to ≥2 antiarrhythmic drugs and drug-resistant hypertension ( systolic blood pressure > 160 mm Hg despite triple drug therapy ) were eligible for enrolment . Consenting patients were r and omized to PVI only or PVI with renal artery denervation . All patients were followed ≥1 year to assess maintenance of sinus rhythm and to monitor changes in blood pressure . RESULTS Twenty-seven patients were enrolled , and 14 were r and omized to PVI only , and 13 were r and omized to PVI with renal artery denervation . At the end of the follow-up , significant reductions in systolic ( from 181 ± 7 to 156 ± 5 , p < 0.001 ) and diastolic blood pressure ( from 97 ± 6 to 87 ± 4 , p < 0.001 ) were observed in patients treated with PVI with renal denervation without significant change in the PVI only group . Nine of the 13 patients ( 69 % ) treated with PVI with renal denervation were AF-free at the 12-month post-ablation follow-up examination versus 4 ( 29 % ) of the 14 patients in the PVI-only group ( p = 0.033 ) . CONCLUSIONS Renal artery denervation reduces systolic and diastolic blood pressure in patients with drug-resistant hypertension and reduces AF recurrences when combined with PVI This r and omized , multicenter study compared the relative efficacy of renal denervation ( RDN ) versus pharmacotherapy alone in patients with true resistant hypertension and assessed the effect of spironolactone addition . We present here the 12-month data . A total of 106 patients with true resistant hypertension were enrolled in this study : 52 patients were r and omized to RDN and 54 patients to the spironolactone addition , with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4 , respectively . Twelve-month results are available in 101 patients . The intention-to-treat analysis found a comparable mean 24-hour systolic blood pressure decline of 6.4 mm Hg , P=0.001 in RDN versus 8.2 mm Hg , P=0.002 in the pharmacotherapy group . Per- protocol analysis revealed a significant difference of 24-hour systolic blood pressure decline between complete RDN ( 6.3 mm Hg , P=0.004 ) and the subgroup where spironolactone was added , and this continued within the 12 months ( 15 mm Hg , P= 0.003 ) . Renal artery computed tomography angiograms before and after 1 year post-RDN did not reveal any relevant changes . This study shows that over a period of 12 months , RDN is safe , with no serious side effects and no major changes in the renal arteries . RDN in the setting s of true resistant hypertension with confirmed compliance is not superior to intensified pharmacological treatment . Spironolactone addition ( if tolerated ) seems to be more effective in blood pressure reduction BACKGROUND Prior studies of catheter-based renal artery denervation have not systematic ally performed ambulatory blood pressure monitoring ( ABPM ) to assess the efficacy of the procedure . OBJECTIVES SYMPLICITY HTN-3 ( Renal Denervation in Patients With Uncontrolled Hypertension ) was a prospect i ve , blinded , r and omized , sham-controlled trial . The current analysis details the effect of renal denervation or a sham procedure on ABPM measurements 6 months post-r and omization . METHODS Patients with resistant hypertension were r and omized 2:1 to renal denervation or sham control . Patients were on a stable antihypertensive regimen including maximally tolerated doses of at least 3 drugs including a diuretic before r and omization . The powered secondary efficacy endpoint was a change in mean 24-h ambulatory systolic blood pressure ( SBP ) . Nondipper to dipper ( nighttime blood pressure [ BP ] 10 % to 20 % lower than daytime BP ) conversion was calculated at 6 months . RESULTS The 24-h ambulatory SBP changed -6.8 ± 15.1 mm Hg in the denervation group and -4.8 ± 17.3 mm Hg in the sham group : difference of -2.0 mm Hg ( 95 % confidence interval [ CI ] : -5.0 to 1.1 ; p = 0.98 with a 2 mm Hg superiority margin ) . The daytime ambulatory SBP change difference between groups was -1.1 ( 95 % CI : -4.3 to 2.2 ; p = 0.52 ) . The nocturnal ambulatory SBP change difference between groups was -3.3 ( 95 CI : -6.7 to 0.1 ; p = 0.06 ) . The percent of nondippers converted to dippers was 21.2 % in the denervation group and 15.0 % in the sham group ( 95 % CI : -3.8 % to 16.2 % ; p = 0.30 ) . Change in 24-h heart rate was -1.4 ± 7.4 in the denervation group and -1.3 ± 7.3 in the sham group ; ( 95 % CI : -1.5 to 1.4 ; p = 0.94 ) . CONCLUSIONS This trial did not demonstrate a benefit of renal artery denervation on reduction in ambulatory BP in either the 24-h or day and night periods compared with sham ( Renal Denervation in Patients With Uncontrolled Hypertension [ SYMPLICITY HTN-3 ] ; NCT01418261 ) BACKGROUND Conflicting blood pressure-lowering effects of catheter-based renal artery denervation have been reported in patients with resistant hypertension . We compared the ambulatory blood pressure-lowering efficacy and safety of radiofrequency-based renal denervation added to a st and ardised stepped-care antihypertensive treatment ( SSAHT ) with the same SSAHT alone in patients with resistant hypertension . METHODS The Renal Denervation for Hypertension ( DENERHTN ) trial was a prospect i ve , open-label r and omised controlled trial with blinded endpoint evaluation in patients with resistant hypertension , done in 15 French tertiary care centres specialised in hypertension management . Eligible patients aged 18 - 75 years received indapamide 1·5 mg , ramipril 10 mg ( or irbesartan 300 mg ) , and amlodipine 10 mg daily for 4 weeks to confirm treatment resistance by ambulatory blood pressure monitoring before r and omisation . Patients were then r and omly assigned ( 1:1 ) to receive either renal denervation plus an SSAHT regimen ( renal denervation group ) or the same SSAHT alone ( control group ) . The r and omisation sequence was generated by computer , and stratified by centres . For SSAHT , after r and omisation , spironolactone 25 mg per day , bisoprolol 10 mg per day , prazosin 5 mg per day , and rilmenidine 1 mg per day were sequentially added from months two to five in both groups if home blood pressure was more than or equal to 135/85 mm Hg . The primary endpoint was the mean change in daytime systolic blood pressure from baseline to 6 months as assessed by ambulatory blood pressure monitoring . The primary endpoint was analysed blindly . The safety outcomes were the incidence of acute adverse events of the renal denervation procedure and the change in estimated glomerular filtration rate from baseline to 6 months . This trial is registered with Clinical Trials.gov , number NCT01570777 . FINDINGS Between May 22 , 2012 , and Oct 14 , 2013 , 1416 patients were screened for eligibility , 106 of those were r and omly assigned to treatment ( 53 patients in each group , intention-to-treat population ) and 101 analysed because of patients with missing endpoints ( 48 in the renal denervation group , 53 in the control group , modified intention-to-treat population ) . The mean change in daytime ambulatory systolic blood pressure at 6 months was -15·8 mm Hg ( 95 % CI -19·7 to -11·9 ) in the renal denervation group and -9·9 mm Hg ( -13·6 to -6·2 ) in the group receiving SSAHT alone , a baseline-adjusted difference of -5·9 mm Hg ( -11·3 to -0·5 ; p=0·0329 ) . The number of antihypertensive drugs and drug-adherence at 6 months were similar between the two groups . Three minor renal denervation-related adverse events were noted ( lumbar pain in two patients and mild groin haematoma in one patient ) . A mild and similar decrease in estimated glomerular filtration rate from baseline to 6 months was observed in both groups . INTERPRETATION In patients with well defined resistant hypertension , renal denervation plus an SSAHT decreases ambulatory blood pressure more than the same SSAHT alone at 6 months . This additional blood pressure lowering effect may contribute to a reduction in cardiovascular morbidity if maintained in the long term after renal denervation . FUNDING French Ministry of Health Renal sympathetic hyperactivity is seminal in the maintenance and progression of hypertension . Catheter-based renal sympathetic denervation has been shown to significantly reduce blood pressure ( BP ) in patients with hypertension . Durability of effect beyond 1 year using this novel technique has never been reported . A cohort of 45 patients with resistant hypertension ( systolic BP ≥160 mm Hg on ≥3 antihypertension drugs , including a diuretic ) has been originally published . Herein , we report longer-term follow-up data on these and a larger group of similar patients subsequently treated with catheter-based renal denervation in a nonr and omized manner . We treated 153 patients with catheter-based renal sympathetic denervation at 19 centers in Australia , Europe , and the United States . Mean age was 57±11 years , 39 % were women , 31 % were diabetic , and 22 % had coronary artery disease . Baseline values included mean office BP of 176/98±17/15 mm Hg , mean of 5 antihypertension medications , and an estimated glomerular filtration rate of 83±20 mL/min per 1.73 m2 . The median time from first to last radiofrequency energy ablation was 38 minutes . The procedure was without complication in 97 % of patients ( 149 of 153 ) . The 4 acute procedural complications included 3 groin pseudoaneurysms and 1 renal artery dissection , all managed without further sequelae . Postprocedure office BPs were reduced by 20/10 , 24/11 , 25/11 , 23/11 , 26/14 , and 32/14 mm Hg at 1 , 3 , 6 , 12 , 18 , and 24 months , respectively . In conclusion , in patients with resistant hypertension , catheter-based renal sympathetic denervation results in a substantial reduction in BP sustained out to ≥2 years of follow-up , without significant adverse events More than 10 % of patients treated for hypertension have persistently uncontrolled blood pressure ( BP ) despite prescription of antihypertensive drugs ( 1 ) . Renal sympathetic denervation is an old concept that has been re-introduced as a new treatment for hypertension that is apparently resistant to drug treatment ( 2 ) . Patients considered eligible for this procedure populate the high end of the BP spectrum , where , for whatever reason , pharmacological treatment has failed to produce adequate BP control . Recent data suggest that patients suspected of having “ resistant hypertension ” in fact represent a mixed group that includes those with white coat hypertension , secondary forms of hypertension , inadequate dosing of medication and poor adherence to prescribed antihypertensive treatment , as well as true resistant hypertension ( 3 ) . Two out of every three patients referred for renal denervation ( RDN ) because of apparent resistant hypertension did not have true resistant hypertension and therefore were not considered eligible for the procedure . Non and poor adherence to prescribed treatment occurred frequently in this referral population , leading the authors to recommend careful screening of patients with apparent resistant hypertension before undertaking RDN procedures . The main aim of such a screening program is to confi rm the persistence of uncontrolled hypertension despite adequate medical treatment and to exclude secondary forms of hypertension . The Symplicity HTN-2 study ( 4 ) was the fi rst r and omized controlled trial of renal sympathetic denervation to be reported in the literature . Symplicity HTN-2 r and omized 106 patients with apparent treatment-resistant hypertension to renal sympathetic denervation or control and followed them for 6 months . Offi ce BPs were reduced by 32/12 mmHg in the intervention group at 6 months and remained unchanged in the control group . Reductions in ambulatory BP were much smaller , suggesting a “ white coat ” effect . Furthermore , drug adherence was not thoroughly investigated . Poor drug adherence is a common problem among patients with apparent treatment-resistant hypertension ( 5,6 ) . For example , a study of 84 patients taking on average fi ve antihypertensive drugs found no detectable blood levels of any antihypertensive drug in 34.5 % of the patients , and that 65.5 % of the patients fulfi lled the criteria of non-adherence ( 7 ) . It is not known to what extent the reduction in BP that is observed following RDN is caused by the denervation per se or by increased drug adherence . It is reasonable to postulate that patients with poor drug adherence who undergo RDN receive so much positive attention at follow-up that they become increasingly coherent to their antihypertensive medications and thus have enhanced BP reductions . Some patients may even discontinue their antihypertensive drugs prior to qualifi cation procedures for RDN and then resume their medication after the procedure . This could not be detected by the methods employed in Symplicity HTN-2 ( 4 ) , and these defi ciencies provided an impetus for the more tightly controlled Symplicity HTN-3 study in the USA , which included a sham operated control group ( 8,9 ) . Drug adherence can be assessed in several ways , e.g. by electronic pill boxes , blood and urine measurements of prescribed drugs , or by written patient ’ s diaries . Measurement of drugs in blood or plasma can provide valuable information ( 7 ) , but is not available in most clinical practice s , and neither patient ’ s diaries as used in Symplicity HTN-2 nor electronic pill boxes are reliable enough to ensure drug intake . The only method that fully ensures true drug intake and permits documentation of the effects of the Blood Pressure , 2014 ; 23 : AIM The aim of this study was to determine long-term results of renal artery denervation for treatment of treatment-resistant hypertension in the SYMPLICITY HTN-2 study . METHODS SYMPLICITY HTN-2 r and omized 106 subjects with treatment-resistant hypertension to renal denervation or medical therapy alone . At 6 months , 37 control subjects crossed over to renal denervation . Office blood pressure measurements , antihypertensive medication use , and safety events were followed every 6 months through 3 years . RESULTS Follow-up was available at 36 months in 40 of 52 subjects in the initial renal denervation group and at 30 months in 30 of 37 subjects who crossed over and received renal denervation at 6 months . Baseline blood pressure was 184 ± 19/99 ± 16 mmHg in all treated subjects . At 30-month post-procedure , systolic blood pressure decreased 34 mmHg ( 95 % CI : -40 , -27 , P < 0.01 ) and diastolic blood pressure decreased 13 mmHg ( 95 % CI : -16 , -10 , P < 0.01 ) . The systolic and diastolic blood pressure reduction at 36 months for the initial renal denervation group was -33 mmHg ( 95 % CI : -40 , -25 , P < 0.01 ) and -14 mmHg ( 95 % CI : -17 , -10 , P < 0.01 ) , respectively . Procedural complications included one haematoma , and one renal artery dissection before energy delivery that was treated successfully . Later complications included two cases of acute renal failure , which fully resolved , 15 hypertensive events requiring hospitalization , and three deaths . CONCLUSION Renal denervation result ed in sustained lowering of blood pressure at 3 years in a selected population of subjects with severe , treatment-resistant hypertension without serious safety concerns . CLINICAL TRIAL REGISTRATION NCT00888433 BACKGROUND Hypertension is the most important risk factor directly attributable to the high prevalence of atrial fibrillation ( AF ) , and is one of the few modifiable risk factors for AF . Activation and overactivity of the sympathetic nervous system ( SNS ) have been implicated in the pathogenesis of both essential hypertension and AF . Catheter-based renal sympathetic denervation ( RSDN ) appears to be an effective adjunctive treatment for refractory hypertension , and may be beneficial in other conditions characterized by SNS overactivity , such as left ventricular hypertrophy and atrial arrhythmias . OBJECTIVE The H-FIB study is a multicenter prospect i ve , double-blind , r and omized ( 1:1 ) controlled trial . The primary efficacy endpoint is antiarrhythmic drug-free freedom from AF recurrence through 12 months . METHODS Patients with a history of significant hypertension who are receiving treatment with at least one antihypertensive agent who are planned for a first time ablation for symptomatic paroxysmal or persistent AF will be r and omized to either AF ablation alone ( control group ) or AF ablation + RSDN ( study group ) . CONCLUSIONS H-FIB is a multicenter , r and omized trial that will test the hypothesis that adjunctive renal sympathetic denervation , at the time of AF ablation , will increase the freedom from recurrent AF This prospect i ve , r and omized , open-label multicenter trial evaluated the efficacy of catheter-based renal denervation ( Symplicity , Medtronic ) versus intensified pharmacological treatment including spironolactone ( if tolerated ) in patients with true-resistant hypertension . This was confirmed by 24-hour ambulatory blood pressure monitoring after excluding secondary hypertension and confirmation of adherence to therapy by measurement of plasma antihypertensive drug levels before enrollment . One-hundred six patients were r and omized to renal denervation ( n=52 ) , or intensified pharmacological treatment ( n=54 ) with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4 , respectively . A significant reduction in 24-hour average systolic blood pressure after 6 months ( −8.6 [ 95 % cofidence interval : −11.8 , −5.3 ] mm Hg ; P<0.001 in renal denervation versus −8.1 [ 95 % cofidence interval : −12.7 , −3.4 ] mm Hg ; P=0.001 in pharmacological group ) was observed , which was comparable in both groups . Similarly , a significant reduction in systolic office blood pressure ( −12.4 [ 95 % cofidence interval : −17.0 , −7.8 ] mm Hg ; P<0.001 in renal denervation versus −14.3 [ 95 % cofidence interval : −19.7 , −8.9 ] mm Hg ; P<0.001 in pharmacological group ) was present . Between-group differences in change were not significant . The average number of antihypertensive drugs used after 6 months was significantly higher in the pharmacological group ( + 0.3 drugs ; P<0.001 ) . A significant increase in serum creatinine and a parallel decrease of creatinine clearance were observed in the pharmacological group ; between-group difference were borderline significant . The 6-month results of this study confirmed the safety of renal denervation . In conclusion , renal denervation achieved reduction of blood pressure comparable with intensified pharmacotherapy Background Recently , catheter-based renal sympathetic denervation ( RSD ) has been verified to be safely used to substantially reduce the levels of blood pressure , left ventricular hypertrophy , sleep apnea severity and norepinephrine spillover , and improve glucose tolerance . All these pathological changes are recognized as independent risk factors for the development and recurrence of atrial fibrillation ( AF ) . A r and omized , single-blind , parallel-control , multicenter clinical trial is being conducted to compare RSD with antiarrhythmic drugs ( AAD ) in patients with drug-resistant hypertension and symptomatic AF ( RSDforAF trial ) . Methods / design Patients with drug-resistant hypertension and symptomatic AF will be r and omized to RSD and the drug treatment groups . Patients will be followed for 12 months until study closure . Up to 200 patients may be enrolled in six medical centers in China . The primary objective is to study the effects of RSD on AF burden and blood pressure in patients with hypertension and symptomatic AF . Discussion RSDforAF trial will test the hypothesis that RSD is superior to AAD in reducing AF burden and blood pressure in patients with drug-resistant hypertension and symptomatic AF.Trial registration Clinical Trials.gov , There are no clinical studies on the effects of catheter-based radiofrequency renal denervation ( RDN ) on renal artery structure using 64-detector computed tomography ( CT ) . A total of 39 patients with resistant hypertension received RDN and 38 patients received drug treatment . Mean systolic pressure and diastolic pressure in the RDN group decreased after 1 , 3 , 6 , and 12 months of procedure ( P<.05 ) and urinary protein level significantly decreased after 6 and 12 months ( P<.05 ) . The diameter , length , and sectional area of the renal artery ; number of cases of atherosclerosis ; and plaque burden of 64-detector CT renal arteriography did not change at 12 months of follow-up ( P<.05 ) , whereas the plaque burden increased significantly in the control group ( P<.05 ) . RDN significantly and persistently reduced blood pressure and decreased urinary protein excretion rate in patients with resistant hypertension and did not exhibit any adverse effect on renal function and renal artery structure AIMS Sympathetic stimulation induces left ventricular hypertrophy and is associated with increased cardiovascular risk . Catheter-based renal denervation ( RDN ) has been shown to reduce sympathetic outflow and blood pressure ( BP ) . The present multi-centre study aim ed to investigate the effect of RDN on anatomic and functional myocardial parameters , assessed by cardiac magnetic resonance ( CMR ) , in patients with resistant hypertension . METHODS AND RESULTS Cardiac magnetic resonance was performed in 72 patients ( mean age 66 ± 10 years ) with resistant hypertension ( 55 patients underwent RDN , 17 served as controls ) at baseline and after 6 months . Clinical data and CMR results were analysed blindly . Renal denervation significantly reduced systolic and diastolic BP by 22/8 mm Hg and left ventricular mass index ( LVMI ) by 7.1 % ( 46.3 ± 13.6 g/m(1.7 ) vs. 43.0 ± 12.6 g/m(1.7 ) , P < 0.001 ) without changes in the control group ( 41.9 ± 10.8 g/m(1.7 ) vs. 42.0 ± 9.7 g/m(1.7 ) , P = 0.653 ) . Ejection fraction ( LVEF ) in patients with impaired LVEF at baseline ( < 50 % ) significantly increased after RDN ( 43 % vs. 50 % , P < 0.001 ) . Left ventricular circumferential strain as a surrogate of diastolic function in the subgroup of patients with reduced strain at baseline increased by 21 % only in the RDN group ( -14.8 vs. -17.9 ; P = 0.001 ) and not in control patients ( -15.5 vs. -16.4 , P = 0.508 ) . CONCLUSIONS Catheter-based RDN significantly reduced BP and LVMI and improved EF and circumferential strain in patients with resistant hypertension , occurring partly BP independently Abstract —High nighttime and early morning blood pressure ( BP ) have been associated with greater risk for cardiovascular events than high clinic or daytime BP . BP is typically highest in the rising hours , when morning activities typically begin . We examined the effect of renal denervation on morning ( 6:00–8:59 AM ) , daytime ( 9:00 AM–8:59 PM ) , and nighttime ( 1:00–5:59 AM ) ambulatory BP . Patient data from 2 prospect i ve , r and omized controlled trials of patients with treatment-resistant , uncontrolled hypertension , one conducted in a US population ( Renal Denervation in Patients With Uncontrolled Hypertension [ SYMPLICITY HTN-3 ] ) and the other in a Japanese population ( SYMPLICITY HTN-Japan [ HTN-Japan ] ) , were analyzed . Patients in SYMPLICITY HTN-3 and HTN-Japan were prescribed a similar number of baseline antihypertensive medications ( 5.2±1.4 versus 4.9±1.6 , P=0.28 ) , but the classes prescribed and changes in prescription varied by study . Among patients treated with renal denervation , although the number of ablation treatments were similar in both studies ( 11.2±2.8 versus 11.5±1.9 , P=0.55 ) , patients in SYMPLICITY HTN-3 were less likely to receive at least 1 four-quadrant ablation treatment ( 25 % versus 82 % , P<0.001 ) . In SYMPLICITY HTN-3 , compared with controls ( n=159 ) , patients treated with renal denervation ( n=325 ) experienced a significantly greater change in morning ( −7.3±19.8 mm Hg , P<0.001 ) and nighttime ( −6.1±18.2 versus −1.6±19.7 mm Hg , P=0.02 ) but not daytime systolic BP ( −7.2±16.2 versus −6.4±18.6 mm Hg , P=0.67 ) . This same trend was observed in the pooled analysis with HTN-Japan . Reduction of BP during these high-risk periods might provide cardiovascular protection in drug-resistant hypertensive patients , although this will need to be proved in future r and omized trials . Clinical trial registration —URL : www . clinical trials.gov ; Unique identifiers : NCT01418261 ( SYMPLICITY HTN-3 ) and NCT01644604 ( HTN-Japan ) AIMS The SYMPLICITY HTN-3 r and omized , blinded , sham-controlled trial confirmed the safety of renal denervation ( RDN ) , but did not meet its primary efficacy endpoint . Prior RDN studies have demonstrated significant and durable reductions in blood pressure . This analysis investigated factors that may help explain these disparate results . METHODS AND RESULTS Patients with resistant hypertension were r and omized 2 : 1 to RDN ( n = 364 ) or sham ( n = 171 ) . The primary endpoint was the difference in office systolic blood pressure ( SBP ) change at 6 months . A multivariable analysis identified predictors of SBP change . Additional analyses examined the influence of medication changes , results in selected subgroups and procedural factors . Between r and omization and the 6-month endpoint , 39 % of patients underwent medication changes . Predictors of office SBP reduction at 6 months were baseline office SBP ≥ 180 mmHg , aldosterone antagonist use , and non-use of vasodilators ; number of ablations was a predictor in the RDN group . Non-African-American patients receiving RDN had a significantly greater change in office SBP than those receiving sham ; -15.2 ± 23.5 vs. -8.6 ± 24.8 mmHg , respectively ( P = 0.012 ) . Greater reductions in office and ambulatory SBP , and heart rate were observed with a higher number of ablations and energy delivery in a four-quadrant pattern . CONCLUSIONS Post hoc analyses , although derived from limited patient cohorts , reveal several potential confounding factors that may partially explain the unexpected blood pressure responses in both the sham control and RDN groups . These hypothesis-generating data further inform the design of subsequent research to evaluate the potential role of RDN in the treatment of resistant hypertension . CLINICAL TRIALS.GOV IDENTIFIER : NCT01418261 Objective : To study the impact of catheter-based renal artery denervation ( RDN ) on change in morning and night systolic BP ( SBP ) defined by ambulatory BP measurements ( ABPM ) 6 months post-r and omization . Design and method : SYMPLICITY HTN-3 and SYMPLICITY HTN-Japan are prospect i ve , r and omized , controlled trials of RDN for treatment of resistant hypertension . However , SYMPLICITY HTN-3 included a blinded , sham control and HTN-Japan control patients were not blinded and continued medical management alone . Patients in both trials were on a stable antihypertensive regimen of at least 3 drugs including a diuretic before r and omization . Average morning SBP ( 7 am to 9 am ) , maximum morning SBP ( between 6 am and 10 am ) , average nocturnal SBP ( 1 am to 6 am ) , average peak nocturnal SBP ( average of 3 highest SBPs between 1 am and 6 am ) and average daytime SBP were calculated using pooled patient-level ABPM data . Six-month change in SBP parameters were compared between RDN and control patients . Results : A total of 386 patients ( 364 from HTN-3 and 22 from Japan ) received RDN and 190 patients were in the control group ( 171 from HTN-3 and 19 from Japan ) . The average morning SBP was reduced -8.0 ± 22.3 mmHg in the RDN group which was significantly more than the change in the control group ( -3.5 ± 22.2 mmHg , p = 0.023 ) . The maximum morning SBP change was -8.6 ± 22.3 mmHg for RDN patients and -4.8 ± 23.8mmHg for controls ( p = 0.072 ) . Furthermore , the change in average nocturnal and average peak nocturnal SBP was significantly greater in the RDN patients compared with the control patients ; -6.3 ± 18.1 vs -1.7 ± 19.2 mmHg , p = 0.008 for average nocturnal SBP and -6.7 ± 20.0 vs -1.3 ± 20.5 mmHg , p = 0.004 for average peak nocturnal SBP . Average daytime SBP change was not significantly between the RDN and control groups ( -7.1 ± 16.0 vs -5.7 ± 18.0 mmHg , p = 0.349 ) . Conclusions : This analysis demonstrated that RDN significantly reduced morning and nighttime SBP compared with control patients suggesting potential benefit of this device approach on cardiovascular protection in drug-resistant hypertension when measurements are captured during higher risk time periods BACKGROUND Activation of renal sympathetic nerves is key to pathogenesis of essential hypertension . We aim ed to assess effectiveness and safety of catheter-based renal denervation for reduction of blood pressure in patients with treatment-resistant hypertension . METHODS In this multicentre , prospect i ve , r and omised trial , patients who had a baseline systolic blood pressure of 160 mm Hg or more ( ≥150 mm Hg for patients with type 2 diabetes ) , despite taking three or more antihypertensive drugs , were r and omly allocated in a one-to-one ratio to undergo renal denervation with previous treatment or to maintain previous treatment alone ( control group ) at 24 participating centres . R and omisation was done with sealed envelopes . Data analysers were not masked to treatment assignment . The primary effectiveness endpoint was change in seated office-based measurement of systolic blood pressure at 6 months . Primary analysis included all patients remaining in follow-up at 6 months . This trial is registered with Clinical Trials.gov , number NCT00888433 . FINDINGS 106 ( 56 % ) of 190 patients screened for eligibility were r and omly allocated to renal denervation ( n=52 ) or control ( n=54 ) groups between June 9 , 2009 , and Jan 15 , 2010 . 49 ( 94 % ) of 52 patients who underwent renal denervation and 51 ( 94 % ) of 54 controls were assessed for the primary endpoint at 6 months . Office-based blood pressure measurements in the renal denervation group reduced by 32/12 mm Hg ( SD 23/11 , baseline of 178/96 mm Hg , p<0·0001 ) , whereas they did not differ from baseline in the control group ( change of 1/0 mm Hg [ 21/10 ] , baseline of 178/97 mm Hg , p=0·77 systolic and p=0·83 diastolic ) . Between-group differences in blood pressure at 6 months were 33/11 mm Hg ( p<0·0001 ) . At 6 months , 41 ( 84 % ) of 49 patients who underwent renal denervation had a reduction in systolic blood pressure of 10 mm Hg or more , compared with 18 ( 35 % ) of 51 controls ( p<0·0001 ) . We noted no serious procedure-related or device-related complications and occurrence of adverse events did not differ between groups ; one patient who had renal denervation had possible progression of an underlying atherosclerotic lesion , but required no treatment . INTERPRETATION Catheter-based renal denervation can safely be used to substantially reduce blood pressure in treatment-resistant hypertensive patients . FUNDING Ardian BACKGROUND Results of the SYMPLICITY HTN-3 ( Renal Denervation in Patients With Uncontrolled Hypertension ) trial confirmed the safety but not the efficacy of renal denervation for treatment-resistant hypertension at 6 months post procedure . OBJECTIVES This study sought to analyze the 12-month SYMPLICITY HTN-3 results for the original denervation group , the sham subjects who underwent denervation after the 6-month endpoint ( crossover group ) , and the sham subjects who did not undergo denervation after 6 months ( non-crossover group ) . METHODS Eligible subjects were r and omized 2:1 to denervation or sham procedure . Subjects were unblinded to their treatment group after the 6-month primary endpoint was ascertained ; subjects in the sham group meeting eligibility requirements could undergo denervation . Change in blood pressure ( BP ) at 12 months post r and omization ( 6 months for crossover subjects ) was analyzed . RESULTS The 12-month follow-up was available for 319 of 361 denervation subjects and 48 of 101 non-crossover subjects ; 6-month denervation follow-up was available for 93 of 101 crossover subjects . In denervation subjects , the 12-month office systolic BP ( SBP ) change was greater than that observed at 6 months ( -15.5 ± 24.1 mm Hg vs. -18.9 ± 25.4 mm Hg , respectively ; p = 0.025 ) , but the 24-h SBP change was not significantly different at 12 months ( p = 0.229 ) . The non-crossover group office SBP decreased by -32.9 ± 28.1 mm Hg at 6 months , but this response regressed to -21.4 ± 19.9 mm Hg ( p = 0.01 ) at 12 months , increasing to 11.5 ± 29.8 mm Hg . CONCLUSIONS These data support no further reduction in office or ambulatory BP after 1-year follow-up . Loss of BP reduction in the non-crossover group may reflect decreased medication adherence or other related factors . ( Renal Denervation in Patients With Uncontrolled Hypertension [ SYMPLICITY HTN-3 ] ; NCT01418261 ) Introduction Despite the ongoing debate on the role of renal sympathetic denervation ( RSD ) in the management of therapy-resistant hypertension , little is known about its possible effects on exercise blood pressure ( BP ) , a known predictor for future cardiovascular events . We sought to evaluate the effect of RSD on exercise BP in a r and omized , sham-controlled trial in patients with mild hypertension . Methods and results Patients with therapy-resistant mild hypertension ( defined by mean daytime systolic BP between 135 and 149 mmHg or mean daytime diastolic BP between 90 and 94 mmHg on 24-h ambulatory BP measurement ) were r and omized to either radiofrequency-based RSD or a sham procedure . Patients underwent cardiopulmonary exercise testing at baseline and after 6 months . Of the 71 patients r and omized , data from cardiopulmonary exercise testing were available for 48 patients ( 22 in the RSD group , 26 in the sham group ) . After 6 months , patients undergoing RSD had a significantly lower systolic BP at maximum exercise workload compared to baseline ( −14.2 ± 26.1 mmHg , p = 0.009 ) . In contrast , no change was observed in the sham group ( 0.6 ± 22.9 mmHg , p = 0.45 , p = 0.04 for between-group comparison ) . When analyzing patients with exaggerated baseline exercise BP only , the effect was even more pronounced ( RSD vs. sham −29.5 ± 23.4 vs. 0.1 ± 25.3 mmHg , p = 0.008 ) . Conclusion Exercise systolic BP values in patients with mild therapy-resistant hypertension are reduced after RSD as compared to a sham-procedure Background — Renal sympathetic nerve activation contributes to the pathogenesis of hypertension . Symplicity HTN-2 , a multicenter , r and omized trial , demonstrated that catheter-based renal denervation produced significant blood pressure lowering in treatment-resistant patients at 6 months after the procedure compared with control , medication-only patients . Longer-term follow-up , including 6-month crossover results , is now presented . Methods and Results — Eligible patients were on ≥3 antihypertensive drugs and had a baseline systolic blood pressure ≥160 mm Hg ( ≥150 mm Hg for type 2 diabetics ) . After the 6-month primary end point was met , renal denervation in control patients was permitted . One-year results on patients r and omized to immediate renal denervation ( n=47 ) and 6-month postprocedure results for crossover patients are presented . At 12 months after the procedure , the mean fall in office systolic blood pressure in the initial renal denervation group ( −28.1 mm Hg ; 95 % confidence interval , −35.4 to −20.7 ; P<0.001 ) was similar to the 6-month fall ( −31.7 mm Hg ; 95 % confidence interval , −38.3 to −25.0 ; P=0.16 versus 6-month change ) . The mean systolic blood pressure of the crossover group 6 months after the procedure was significantly lowered ( from 190.0±19.6 to 166.3±24.7 mm Hg ; change , −23.7±27.5 ; P<0.001 ) . In the crossover group , there was 1 renal artery dissection during guide catheter insertion , before denervation , corrected by renal artery stenting , and 1 hypotensive episode , which resolved with medication adjustment . Conclusions — Control patients who crossed over to renal denervation with the Symplicity system had a significant drop in blood pressure similar to that observed in patients receiving immediate denervation . Renal denervation provides safe and sustained reduction of blood pressure to 1 year . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00888433 Abstract The SYMPLICITY studies showed that renal denervation ( RDN ) is feasible as novel treatment for resistant hypertension . However , RDN is a costly and invasive procedure , the long-term efficacy and safety of which has not yet been proven . Therefore , we design ed the INSPiRED trial to compare the blood pressure lowering efficacy and safety of RDN vs usual medical therapy . INSPiRED is a r and omized controlled trial enrolling 240 treatment-resistant hypertensive patients at 16 expert hypertension centres in Belgium . Eligible patients , aged 20–69 years old , have a 24-h ambulatory blood pressure of 130 mmHg systolic or 80 mmHg diastolic or more , while taking at least three antihypertensive drugs . They are r and omized to RDN ( EnligHTNTM , SJM system ) plus usual care ( intervention group ) or usual care alone ( control group ) in a ratio of 1:1 . The primary endpoints for efficacy and safety , measured after 6 months , are the baseline-adjusted between-group differences in 24h systolic blood pressure and in glomerular filtration rate as estimated by the Chronic Kidney Disease Epidemiology Collaboration equation . Follow-up will continue up to 36 months after r and omization . INSPiRED is powered to demonstrate a 10-mmHg difference in systolic blood pressure between r and omized groups with a two-sided p-value of 0.01 and 90 % power . It will generate long-term efficacy and safety data , identify the subset of treatment-resistant hypertensive patients responsive to RDN , provide information on cost-effectiveness , and by doing so INSPiRED will inform guideline committees and health policy makers . Trial registration : Clinical Trials.gov identifier : NCT01505010 BACKGROUND Renal denervation ( RDN ) with radiofrequency ablation substantially reduces blood pressure in patients with treatment-resistant hypertension . We assessed the long-term antihypertensive effects and safety . METHODS Symplicity HTN-1 is an open-label study that enrolled 153 patients , of whom 111 consented to follow-up for 36 months . Eligible patients had a systolic blood pressure of at least 160 mm Hg and were taking at least three antihypertensive drugs , including a diuretic , at the optimum doses . Changes in office systolic blood pressure and safety were assessed every 6 months and reported every 12 months . This study is registered with Clinical Trials.gov , numbers NCT00483808 , NCT00664638 , and NCT00753285 . FINDINGS 88 patients had complete data at 36 months . At baseline the mean age was 57 ( SD 11 ) years , 37 ( 42 % ) patients were women , 25 ( 28 % ) had type 2 diabetes mellitus , the mean estimated glomerular filtration rate was 85 ( SD 19 ) mL/min per 1·73 m(2 ) , and mean blood pressure was 175/98 ( SD 16/14 ) mm Hg . At 36 months significant changes were seen in systolic ( -32·0 mm Hg , 95 % CI -35·7 to -28·2 ) and diastolic blood pressure ( -14·4 mm Hg , -16·9 to -11·9 ) . Drops of 10 mm Hg or more in systolic blood pressure were seen in 69 % of patients at 1 month , 81 % at 6 months , 85 % at 12 months , 83 % at 24 months , and 93 % at 36 months . One new renal artery stenosis requiring stenting and three deaths unrelated to RDN occurred during follow-up . INTERPRETATION Changes in blood pressure after RDN persist long term in patients with treatment-resistant hypertension , with good safety . FUNDING Ardian LLC/Medtronic SYMPLICITY HTN-3 , the first trial of renal denervation ( RDN ) versus sham , enrolled 26 % African Americans , a prospect ively stratified cohort . Although the 6-month systolic blood pressure ( SBP ) reduction in African Americans ( AAs ) was similar in the RDN group ( -15.5 ± 25.4 mm Hg , n = 85 vs. -17.8 ± 29.2 , n = 49 , P = .641 ) , the sham SBP response was 9.2 mm Hg greater ( P = .057 ) in AAs than non-AAs . In multivariate analyses , sham SBP response was predicted by an interaction between AA and a complex antihypertensive regimen ( at least one antihypertensive medication prescribed ≥3 times daily ) , while in the RDN group , SBP response was predicted by an interaction between AA race and baseline BP ≥ 180 mm Hg . AA race did not independently predict SBP response in either sham or RDN . There appears to be effect modification by race with individual-level patient characteristics in both treatment arms that affect the observed pattern of SBP responses Background Heart failure with preserved ejection fraction ( HF-PEF ) is common and has a poor prognosis with a 3 year mortality rate of 23 % . There are currently no effective therapies for this condition . HF-PEF is characterized by symptoms of heart failure , normal or a mildly impaired ejection fraction and evidence of adverse cardiac and vascular remodelling . A feature of all heart failure is a heightened sympathetic nervous system ( SNS ) , which can now be abrogated using renal denervation ( RD ) . Methods We are conducting a study of patients with HF-PEF who will be r and omised ( 2:1 ) to receive RD or open control . As a phase II mechanistic study we are primarily investigating the effect of RD on patient symptoms ( question naire ) , cardio-pulmonary exercise function , B-type natriuretic peptide levels , left ventricular filling pressures , left ventricular mass and left atrial volume . We are also assessing macrovascular function using aorta imaging to calculate aorta distensibility , pulse wave velocity and aortic flow . Finally Objective : Actual procedure of renal denervation ( RD ) in Symplicity HTN-3 study - 4–6 point ablations equally distributed along the length and circumference of main trunk of renal artery ( RA ) - may only be effective if renal nerves are likewise equally distributed along and around the RA strictly following its course . However , a number of surgical studies demonstrated that renal nerves form a fan-shaped triangle plexus converging toward hilum , i.e. proximally the nerves go at a distance from RA obliquely to its course and join it in the middle/distal portion so that number of fibers available for endovascular ablation is small in proximal portion of RA but rises to maximum in its distal part . To evaluate whether ablation of sympathetic nerves in distal part of RA is more effective than conventional RD treatment equally distributed in its main trunk . Design and method : We initiated r and omized ( 1:1 ) controlled study in which we compare the modified operative technique ( ablations performed in distal part and major branches of RA ) with conventional RD in patients with resistant hypertension using Symplicity device . Results : At the time of this analysis 26 patients ( 13 treated by modified technique and 13 – by conventional RD ) completed 6 months follow up . The only complication was 1 post-punctional pseudoaneurysm . Ambulatory BP decreased significantly in the group of modified technique : -21.3/-11.5 ( SD 20.5/11.2 ) mmHg ( mean 24-hr BP , systolic/diastolic respectively ) , p = 0.003/0.003 and only slightly in the group of st and ard RD : -6.2/-4.5 ( SD 16.4/8.3 ) p = 0.19/0.07 . The difference in the effects was statistically significant for mean 24-h systolic BP ( p = 0.049 ) and close to significance for mean 24-h diastolic BP ( p = 0.085 ) . Office BP lowering did not differ significantly between groups : -25.3/-10.8 vs -22.1/-12.1 respectively . Conclusions : Radiofrequency denervation of distal part and segmental branches of renal artery based on the surgical findings of distal convergence of renal nerves seems to be significantly more effective than existed mode of RD presuming equal nerve availability along the artery . This may indicate anatomical inadequacy of the existed mode of RD explaining its failure in Symplicity HTN-3 trial Objective : The French DENERHTN trial has shown that renal denervation ( RDN , Symplicity Catheter ) in addition to st and ardized optimal medical treatment ( SOMT ) decreases ambulatory BP more ( 6 mmHg ) than the same SOMT alone at 6 months in patients ( pts ) with resistant hypertension ( RH ) . However , some pts did not respond to RDN or SOMT at 6 months . The aim of the study was to determine the prevalence and characteristics of refractory hypertension ( RFH ) to more than 5 antihypertensive treatments at 6 months in the 2 groups . Design and method : Pts with RH to > = 3 antihypertensive drugs , including a diuretic , entered a 4-week st and ardised triple treatment with indapamide 1.5 mg/day , ramipril 10 mg/day ( or irbesartan 300 mg/day if cough ) , and amlodipine ( 10 mg/day ) . After 4 weeks , pts with daytime ambulatory SBP/DBP ( dASBP/dADBP ) > = 135 or 85 mmHg were r and omised to the RDN or control group . After r and omisation , the SOMT included : spironolactone ( 25 mg/day ) , bisoprolol ( 10 mg/day ) , prazosin ( 5 mg/day ) , and rilmenidine ( 1 mg/day ) sequentially added if home BP ( HBP ) was > = 135 or 85 mmHg at month 2 , 3 , 4 and 5 . Results : 49/97 pts ( 50.5 % ) had RFH at 6 months ( RDN : 20/44 , 45.5 % vs. control : 28/53 , 52.8 % ; p = 0.157 ) . RFH pts were more frequently women , had more frequently OSA , had higher baseline BP values , responded less to any intervention ( RDN + SOMT or SOMT alone ) despite receiving more antihypertensive treatments , had lower plasma creatinine at baseline . The Morisky adherence score was lower ( p = 0.085 ) at baseline than at 6 months in the RFH group . Figure . No caption available . Conclusions : In conclusion , despite following strictly ESH guidelines for treating patients with RH to a triple therapy , around 50 % of the pts have RFH after 6 months follow-up in the DENERHTN trial . Female gender , high BP , low plasma creatinine , and lower adherence at baseline were associated with RFH Hypertension represents a significant global public health concern , contributing to vascular and renal morbidity , cardiovascular mortality , and economic burden . The opportunity to influence clinical outcomes through hypertension management is therefore paramount . Despite adherence to multiple available medical therapies , a significant proportion of patients have persistent blood pressure elevation , a condition termed resistant hypertension . Recent recognition of the importance of the renal sympathetic and somatic nerves in modulating blood pressure and the development of a novel procedure that selectively removes these contributors to resistant hypertension represents an opportunity to provide clinical ly meaningful benefit across wide and varied patient population s. Early clinical evaluation with catheter‐based , selective renal sympathetic denervation in patients with resistant hypertension has mechanistically correlated sympathetic efferent denervation with decreased renal norepinephrine spillover and renin activity , increased renal plasma flow , and has demonstrated clinical ly significant , sustained reductions in blood pressure . The SYMPLICITY HTN‐3 Trial is a pivotal study design ed as a prospect i ve , r and omized , masked procedure , single‐blind trial evaluating the safety and effectiveness of catheter‐based bilateral renal denervation for the treatment of uncontrolled hypertension despite compliance with at least 3 antihypertensive medications of different classes ( at least one of which is a diuretic ) at maximal tolerable doses . The primary effectiveness endpoint is measured as the change in office‐based systolic blood pressure from baseline to 6 months . This manuscript describes the design and methodology of a regulatory trial of selective renal denervation for the treatment of hypertension among patients who have failed pharmacologic therapy . Clin . Cardiol . 2012 . doi : BACKGROUND SYMPLICITY HTN-Japan is a prospect i ve , r and omized , controlled trial comparing renal artery denervation ( RDN ) with st and ard pharmacotherapy for treatment of resistant hypertension ( systolic blood pressure [ SBP ] ≥160 mmHg on ≥3 anti-hypertensive drugs including a diuretic for ≥6 weeks ) . When SYMPLICITY HTN-3 failed to meet the primary efficacy endpoint , the HTN-Japan enrollment was discontinued before completion . METHODS AND RESULTS : The 6-month change in office and 24-h ambulatory SBP were compared between RDN ( n=22 ) and control ( n=19 ) subjects . Mean baseline office SBP was 181.0±18.0 mmHg and 178.7±17.8 mmHg for the RDN and control groups , respectively . The 6-month office SBP change was -16.6±18.5 mmHg for RDN subjects ( P<0.001 ) and -7.9±21.0 mmHg for control subjects ( P=0.117 ) ; the difference between the 6-month change in RDN and control subjects was -8.64 ( 95 % CI : -21.12 to 3.84 , P=0.169 ) . Mean 24-h SBP was 164.7±18.3 ( RDN group ) and 163.3±17.2 mmHg ( control group ) . The 24-h 6-month SBP change for the RDN group was -7.52±11.98 mmHg ( P=0.008 ) and -1.38±10.2 mmHg ( P=0.563 ) for control subjects ; the between-group difference in SBP change was -6.15 ( 95 % CI : -13.23 to 0.94 , P=0.087 ) . No major adverse events were reported . CONCLUSIONS SYMPLICITY HTN-Japan , the first r and omized controlled trial of RDN in an Asian population , was underpowered for the primary endpoint analysis and did not demonstrate a significant difference in 6-month BP change between RDN and control subjects |
12,967 | 28,489,279 | AUTHORS ' CONCLUSIONS There is no firm evidence that DPP-4 inhibitors or GLP-1 analogues compared mainly with placebo substantially influence the risk of T2DM and especially its associated complications in people at increased risk for the development of T2DM . | BACKGROUND The projected rise in the incidence of type 2 diabetes mellitus ( T2DM ) could develop into a substantial health problem worldwide .
Whether dipeptidyl-peptidase (DPP)-4 inhibitors or glucagon-like peptide (GLP)-1 analogues are able to prevent or delay T2DM and its associated complications in people at risk for the development of T2DM is unknown .
OBJECTIVES To assess the effects of DPP-4 inhibitors and GLP-1 analogues on the prevention or delay of T2DM and its associated complications in people with impaired glucose tolerance , impaired fasting blood glucose , moderately elevated glycosylated haemoglobin A1c ( HbA1c ) or any combination of these . | OBJECTIVE Endothelial dysfunction is frequently present in individuals with insulin resistance or type 2 diabetes and can be induced by high-fat or high-carbohydrate meals . Because exenatide reduces postpr and ial glucose and lipid excursions , we hypothesized that it may also improve postpr and ial endothelial function . RESEARCH DESIGN AND METHODS In a double-blinded r and omized crossover design , postpr and ial endothelial function was examined in 28 individuals with impaired glucose tolerance or recent-onset type 2 diabetes after a single injection of exenatide or placebo given just before a high-fat meal . Endothelial function was determined with peripheral arterial tonometry pre- and postpr and ially . RESULTS Postpr and ial endothelial function was higher after exenatide compared with placebo ( P = 0.0002 ) . In the placebo phase , postpr and ial change in endothelial function was inversely associated with mean postpr and ial concentrations of triglycerides ( r = −0.62 , P = 0.0004 ) . Changes in postpr and ial triglyceride concentrations explained 64 % of exenatide 's effect on postpr and ial endothelial function . CONCLUSIONS Exenatide ameliorates postpr and ial endothelial dysfunction after a high-fat meal Introduction Pregnancy is associated with decreased insulin sensitivity , which is usually overcome by a compensatory increase in insulin secretion . Some pregnant women are not able to increase their insulin secretion sufficiently , and consequently develop gestational diabetes mellitus ( GDM ) . The disease normally disappears after delivery . Nevertheless , women with previous GDM have a high risk of developing type 2 diabetes ( T2D ) later in life . We aim to investigate the early development of T2D in women with previous GDM and to evaluate whether treatment with the glucagon-like peptide-1 receptor ( GLP-1R ) agonist , liraglutide , may modify their risk of developing T2D . Methods and analyses 100 women with previous GDM will be r and omised to either liraglutide or placebo treatment for 1 year ( blinded ) with an open-label extension for another 4 years . Additionally , 15 women without previous GDM will constitute a baseline control group . Women will be tested with an oral glucose tolerance test ( primary endpoint : area under the curve for plasma glucose ) and an isoglycaemic intravenous glucose infusion at baseline , after 1 year and after 5 years . Additional evaluations include a glucagon test , dual-energy X-ray absorptiometry , imaging of the liver ( ultrasound elastography and fibroscanning ) , an ad libitum meal for food intake evaluation and question naires related to appetite , quality of life and alcohol consumption habits . Ethics and dissemination The protocol has been approved by the Danish Medicines Agency , the Scientific-Ethical Committee of the Capital Region of Denmark , and the Danish Data Protection Agency and will be carried out under the surveillance and guidance of the GCP unit at Copenhagen University Hospital Bispebjerg in compliance with the ICH-GCP guidelines and in accordance with the Helsinki Declaration . Positive , negative and inconclusive results will be published at scientific conferences and as one or more scientific manuscripts in peer- review ed journals . Registration s The trial is registered at https://eudract.ema.europa.eu ( 2012 - 001371 - 37 ) and http://www . clinical trials.gov ( NCT01795248 ) Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged PURPOSE We aim ed to assess the impact of spin ( ie , reporting to convince readers that the beneficial effect of the experimental treatment is greater than shown by the results ) on the interpretation of results of abstract s of r and omized controlled trials ( RCTs ) in the field of cancer . METHODS We performed a two-arm , parallel-group RCT . We selected a sample of published RCTs with statistically nonsignificant primary outcome and with spin in the abstract conclusion . Two versions of these abstract s were used-the original with spin and a rewritten version without spin . Participants were clinician corresponding authors of articles reporting RCTs , investigators of trials , and review ers of French national grants . The primary outcome was clinicians ' interpretation of the beneficial effect of the experimental treatment ( 0 to 10 scale ) . Participants were blinded to study hypothesis . RESULTS Three hundred clinicians were r and omly assigned using a Web-based system ; 150 clinicians assessed an abstract with spin and 150 assessed an abstract without spin . For abstract s with spin , the experimental treatment was rated as being more beneficial ( mean difference , 0.71 ; 95 % CI , 0.07 to 1.35 ; P = .030 ) , the trial was rated as being less rigorous ( mean difference , -0.59 ; 95 % CI , -1.13 to 0.05 ; P = .034 ) , and clinicians were more interested in reading the full-text article ( mean difference , 0.77 ; 95 % CI , 0.08 to 1.47 ; P = .029 ) . There was no statistically significant difference in the clinicians ' rating of the importance of the study or the need to run another trial . CONCLUSION Spin in abstract s can have an impact on clinicians ' interpretation of the trial results BACKGROUND & AIMS Uncontrolled studies show sitagliptin , an oral DPP-4 inhibitor , may improve alanine aminotransferase and liver histology in non-alcoholic fatty liver disease ( NAFLD ) patients . We aim ed to compare sitagliptin vs. the efficacy of a placebo in reducing liver fat measured by MRI-derived proton density-fat fraction ( MRI-PDFF ) . METHODS This r and omized , double-blind , allocation-concealed , placebo-controlled trial included 50 NAFLD patients with prediabetes or early diabetes r and omized to sitagliptin orally 100mg/day or placebo for 24weeks . Primary outcome was liver fat change measured by MRI-PDFF in colocalized regions of interest within each of nine liver segments . Additional advanced assessment s included MR spectroscopy ( MRS ) for internal validation of MRI-PDFF 's accuracy , and magnetic resonance elastography ( MRE ) and FIBROSpect ® II to assess liver fibrosis . RESULTS Sitagliptin was not significantly better than placebo in reducing liver fat measured by MRI-PDFF ( mean difference between sitagliptin and placebo arms : -1.3 % , p=0.4 ) . Compared to baseline , there were no significant differences in end-of-treatment MRI-PDFF for sitagliptin ( 18.1 % to 16.9 % , p=0.27 ) or placebo ( 16.6 % to 14.0 % , p=0.07 ) . The groups had no significant differences for changes in alanine aminotransferase , aspartate aminotransferase , low-density lipoprotein , homeostatic model assessment insulin resistance , and MRE-derived liver stiffness . In both groups at baseline and post-treatment , MRI-PDFF and MRS showed robust correlation coefficients ranging from r(2)=0.96 to r(2)=0.99 ( p<0.0001 ) , demonstrating the strong internal validity of the findings . FIBROSpect ® II showed no changes in the sitagliptin group but was significantly increased in the placebo group ( p=0.03 ) . CONCLUSIONS Sitagliptin was safe but not better than placebo in reducing liver fat in prediabetic or diabetic patients with NAFLD . LAY SUMMARY In a r and omized , double-blind , placebo-controlled study , the anti-diabetic drug sitagliptin was no more effective than placebo for improving liver fat and liver fibrosis in patients with non-alcoholic fatty liver disease . This study demonstrates that non-invasive magnetic resonance imaging techniques , including magnetic resonance imaging-proton density-fat fraction and magnetic resonance elastography , can be used to assess treatment response in non-alcoholic fatty liver disease clinical trials BACKGROUND The cardiovascular safety and efficacy of many current antihyperglycemic agents , including saxagliptin , a dipeptidyl peptidase 4 ( DPP-4 ) inhibitor , are unclear . METHODS We r and omly assigned 16,492 patients with type 2 diabetes who had a history of , or were at risk for , cardiovascular events to receive saxagliptin or placebo and followed them for a median of 2.1 years . Physicians were permitted to adjust other medications , including antihyperglycemic agents . The primary end point was a composite of cardiovascular death , myocardial infa rct ion , or ischemic stroke . RESULTS A primary end-point event occurred in 613 patients in the saxagliptin group and in 609 patients in the placebo group ( 7.3 % and 7.2 % , respectively , according to 2-year Kaplan-Meier estimates ; hazard ratio with saxagliptin , 1.00 ; 95 % confidence interval [ CI ] , 0.89 to 1.12 ; P=0.99 for superiority ; P<0.001 for noninferiority ) ; the results were similar in the " on-treatment " analysis ( hazard ratio , 1.03 ; 95 % CI , 0.91 to 1.17 ) . The major secondary end point of a composite of cardiovascular death , myocardial infa rct ion , stroke , hospitalization for unstable angina , coronary revascularization , or heart failure occurred in 1059 patients in the saxagliptin group and in 1034 patients in the placebo group ( 12.8 % and 12.4 % , respectively , according to 2-year Kaplan-Meier estimates ; hazard ratio , 1.02 ; 95 % CI , 0.94 to 1.11 ; P=0.66 ) . More patients in the saxagliptin group than in the placebo group were hospitalized for heart failure ( 3.5 % vs. 2.8 % ; hazard ratio , 1.27 ; 95 % CI , 1.07 to 1.51 ; P=0.007 ) . Rates of adjudicated cases of acute and chronic pancreatitis were similar in the two groups ( acute pancreatitis , 0.3 % in the saxagliptin group and 0.2 % in the placebo group ; chronic pancreatitis , < 0.1 % and 0.1 % in the two groups , respectively ) . CONCLUSIONS DPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events , though the rate of hospitalization for heart failure was increased . Although saxagliptin improves glycemic control , other approaches are necessary to reduce cardiovascular risk in patients with diabetes . ( Funded by AstraZeneca and Bristol-Myers Squibb ; SAVOR-TIMI 53 Clinical Trials.gov number , NCT01107886 . ) OBJECTIVE To assess the effects of exenatide on body weight and glucose tolerance in nondiabetic obese subjects with normal or impaired glucose tolerance ( IGT ) or impaired fasting glucose ( IFG ) . RESEARCH DESIGN AND METHODS Obese subjects ( n = 152 ; age 46 ± 12 years , female 82 % , weight 108.6 ± 23.0 kg , BMI 39.6 ± 7.0 kg/m2 , IGT or IFG 25 % ) were r and omized to receive exenatide ( n = 73 ) or placebo ( n = 79 ) , along with lifestyle intervention , for 24 weeks . RESULTS Exenatide-treated subjects lost 5.1 ± 0.5 kg from baseline versus 1.6 ± 0.5 kg with placebo ( exenatide − placebo , P < 0.001 ) . Placebo-subtracted difference in percent weight reduction was −3.3 ± 0.5 % ( P < 0.001 ) . Both groups reduced their daily calorie intake ( exenatide , −449 cal ; placebo , −387 cal ) . IGT or IFG normalized at end point in 77 and 56 % of exenatide and placebo subjects , respectively . CONCLUSIONS Exenatide plus lifestyle modification decreased caloric intake and result ed in weight loss in nondiabetic obesity with improved glucose tolerance in subjects with IGT and IFG Aims To evaluate the efficacy and tolerability of sitagliptin in subjects with impaired glucose tolerance ( IGT ) . Methods In a double‐blind , parallel‐group study , 242 Japanese subjects with IGT , determined by a 75‐g oral glucose tolerance test ( OGTT ) at week −1 , were r and omized ( 1 : 1 : 1 ) to placebo ( n = 83 ) , sitagliptin 25 mg ( n = 82 ) or 50 mg ( n = 77 ) once daily for 8 weeks . Glycaemic variables were assessed using another OGTT at week 7 and meal tolerance tests ( MTTs ) at weeks 0 and 8 . Primary and secondary endpoints were percent change from baseline in glucose total area under the curve 0–2 h ( AUC0 –2 h ) during the MTT and OGTT , respectively . Results Least squares mean percent change from baseline in glucose AUC0 –2 h during the MTT were −2.4 , −9.5 and −11.5 % , and during the OGTT were −3.7 , −21.4 and −20.1 % with placebo , sitagliptin 25 mg once daily , and 50 mg once daily , respectively ( p < 0.001 for either sitagliptin dose vs placebo in both tests ) . Sitagliptin treatment enhanced early insulin response during the OGTT and decreased total insulin response , assessed as the total AUC0 –2 h during the MTT . Sitagliptin treatment also suppressed glucagon response during the MTT . The incidence of adverse events , including hypoglycaemia , was low and generally similar in all treatment groups . Conclusions Treatment with sitagliptin significantly reduced glucose excursions during both an MTT and an OGTT ; this effect was associated with an increase in early insulin secretion after oral glucose loading as well as a blunted glucagon response during an MTT . Sitagliptin was generally well tolerated in subjects with IGT Background Impaired glucose tolerance is present in one third of patients with a TIA or ischemic stroke and is associated with a two-fold risk of recurrent stroke . Metformin improves glucose tolerance , but often leads to side effects . The aim of this study is to explore the feasibility , safety , and effects on glucose metabolism of metformin and sitagliptin in patients with TIA or minor ischemic stroke and impaired glucose tolerance . We will also assess whether a slow increase in metformin dose and better support and information on this treatment will reduce the incidence of side effects in these patients . Methods / Design The Metformin and sitAgliptin in patients with impAired glucose tolerance and a recent TIA or minor ischemic Stroke trial ( MAAS trial ) is a phase II , multicenter , r and omized , controlled , open-label trial with blinded outcome assessment . Non-diabetic patients ( n = 100 ) with a recent ( < 6 months ) TIA , amaurosis fugax or minor ischemic stroke ( modified Rankin scale ≤ 3 ) and impaired glucose tolerance , defined as 2-hour post-load glucose levels between 7.8 and 11.0 mmol/L after repeated st and ard oral glucose tolerance test , will be included . Patients with renal or liver impairment , heart failure , chronic hypoxic lung disease stage III – IV , history of lactate acidosis or diabetic ketoacidosis , pregnancy or breastfeeding , pancreatitis and use of digoxin will be excluded . The patients will be r and omly assigned in a 1:1:2 ratio to metformin , sitagliptin or “ no treatment . ” Patients allocated to metformin will start with 500 mg twice daily , which will be slowly increased during a 6-week period to a twice daily dose of 1000 mg . Patients allocated to sitagliptin will be treated with a daily fixed dose of 100 mg . The study has been registered as NTR 3196 in The Netherl and s Trial Register . Primary outcomes include percentage still on treatment , percentage of ( serious ) adverse events , and the baseline adjusted difference in 2-hour post-load glucose levels at 6 months . Discussion This study will give more information about the feasibility and safety of metformin and sitagliptin as well as the effect on 2-hour post-load glucose levels at 6 months in patients with TIA or ischemic stroke and impaired glucose tolerance . Trial registration numberNTR3196 , Date of registration : 15 December 2011 Background Metabolic disturbances , obesity and life-shortening cardiovascular morbidity are major clinical problems among patients with antipsychotic treatment . Especially two of the most efficacious antipsychotics , clozapine and olanzapine , cause weight gain and metabolic disturbances . Additionally , patients with schizophrenia-spectrum disorders not infrequently consume alcohol . Glucagon-like peptide-1 ( GLP-1 ) has shown to improve glycaemic control and reduce alcohol intake among patients with type 2 diabetes . Objectives To investigate whether the beneficial effects of GLP-1 analogues on glycaemic control and alcohol intake , in patients with type 2 diabetes , can be extended to a population of pre-diabetic psychiatric patients receiving antipsychotic treatment . Methods and analysis Trial design , intervention and participants : The study is a 16-week , double-blinded , r and omised , parallel-group , placebo-controlled clinical trial , design ed to evaluate the effects of the GLP-1 analogue liraglutide on glycaemic control and alcohol intake compared to placebo in patients who are prediabetic , overweight ( body mass index ≥27 kg/m2 ) , diagnosed with a schizophrenia-spectrum disorder and on stable treatment with either clozapine or olanzapine . Outcomes : The primary endpoint is the change in glucose tolerance from baseline ( measured by area under the curve for the plasma glucose excursion following a 4 h 75 g oral glucose tolerance test ) to follow-up at week 16 . The secondary endpoints include changes of dysglycaemia , body weight , waist circumference , blood pressure , secretion of incretin hormones , insulin sensitivity and β cell function , dual-energy X-ray absorption scan ( body composition ) , lipid profile , liver function and measures of quality of life , daily functioning , severity of the psychiatric disease and alcohol consumption from baseline to follow-up at week 16 . Status : Currently recruiting patients . Ethics and dissemination Ethical approval has been obtained . Before screening , all patients will be provided oral and written information about the trial . The study will be disseminated by peer- review publications and conference presentations . Trial registration number Clinical Trials.gov : NCT01845259 , EudraCT : 2013 - 000121 - 31 OBJECTIVE The study aims to provide information about variance components of psychosocial outcomes : within and between-participant variance , within-participant correlation and for cluster r and omised trials , the intra-cluster correlation ( ICC ) and , also , to demonstrate how estimates of these variance components and ICCs can be used to design r and omised trials and cluster r and omised trials . METHOD Data from 15 longitudinal multi-centre psycho-oncology studies were analysed , and variance components including ICCs were estimated . Studies with psychosocial outcomes that had at least one measurement post-baseline including individual r and omised controlled trials , cluster r and omised trials and observational studies were included . RESULTS Variance components and ICCs from 87 outcome measures were estimated . The unadjusted , single timepoint ( first post-baseline ) ICCs ranged from 0 to 0.16 , with a median value of 0.022 and inter-quartile range 0 to 0.0605 . The longitudinal ICCs ranged from 0 to 0.09 with a median value of 0.0007 and inter-quartile range 0 to 0.018 . CONCLUSIONS Although the magnitude of variance components and ICCs used for sample -size calculation can not be known in advance of the study , published estimates can help reduce the uncertainty in sample -size calculations . Psycho-oncology research ers should be conservative in their sample -size calculations and use approaches that improve efficiency in their design and analysis OBJECTIVE The aim was to evaluate the ability of liraglutide to augment weight loss and improve insulin resistance , cardiovascular disease ( CVD ) risk factors , and inflammation in a high-risk population for type 2 diabetes ( T2DM ) and CVD . RESEARCH DESIGN AND METHODS We r and omized 68 older individuals ( mean age , 58 ± 8 years ) with overweight/obesity and prediabetes to this double-blind study of liraglutide 1.8 mg versus placebo for 14 weeks . All subjects were advised to decrease calorie intake by 500 kcal/day . Peripheral insulin resistance was quantified by measuring the steady-state plasma glucose ( SSPG ) concentration during the insulin suppression test . Traditional CVD risk factors and inflammatory markers also were assessed . RESULTS Eleven out of 35 individuals ( 31 % ) assigned to liraglutide discontinued the study compared with 6 out of 33 ( 18 % ) assigned to placebo ( P = 0.26 ) . Subjects who continued to use liraglutide ( n = 24 ) lost twice as much weight as those using placebo ( n = 27 ; 6.8 vs. 3.3 kg ; P < 0.001 ) . Liraglutide-treated subjects also had a significant improvement in SSPG concentration ( −3.2 vs. 0.2 mmol/L ; P < 0.001 ) and significantly ( P ≤ 0.04 ) greater lowering of systolic blood pressure ( −8.1 vs. −2.6 mmHg ) , fasting glucose ( −0.5 vs. 0 mmol/L ) , and triglyceride ( −0.4 vs. −0.1 mmol/L ) concentration . Inflammatory markers did not differ between the two groups , but pulse increased after liraglutide treatment ( 6.4 vs. −0.9 bpm ; P = 0.001 ) . CONCLUSIONS The addition of liraglutide to calorie restriction significantly augmented weight loss and improved insulin resistance , systolic blood pressure , glucose , and triglyceride concentration in this population at high risk for development of T2DM and CVD Objective : Having demonstrated short-term weight loss with liraglutide in this group of obese adults , we now evaluate safety/tolerability ( primary outcome ) and long-term efficacy for sustaining weight loss ( secondary outcome ) over 2 years . Design : A r and omized , double-blind , placebo-controlled 20-week study with 2-year extension ( sponsor unblinded at 20 weeks , participants /investigators at 1 year ) in 19 European clinical research centers . Subjects : A total of 564 adults ( n=90–98 per group ; body mass index 30–40 kg m−2 ) enrolled , 398 entered the extension and 268 completed the 2-year trial . Participants received diet ( 500 kcal deficit per day ) and exercise counseling during 2-week run-in , before being r and omly assigned ( with a telephone or web-based system ) to once-daily subcutaneous liraglutide ( 1.2 , 1.8 , 2.4 or 3.0 mg , n=90–95 ) , placebo ( n=98 ) or open-label orlistat ( 120 mg × 3 , n=95 ) . After 1 year , liraglutide/placebo recipients switched to liraglutide 2.4 mg , then 3.0 mg ( based on 20-week and 1-year results , respectively ) . The trial ran from January 2007–April 2009 and is registered with Clinical trials.gov , number NCT00480909 . Results : From r and omization to year 1 , liraglutide 3.0 mg recipients lost 5.8 kg ( 95 % confidence interval 3.7–8.0 ) more weight than those on placebo and 3.8 kg ( 1.6–6.0 ) more than those on orlistat ( P⩽0.0001 ; intention-to-treat , last-observation-carried-forward ) . At year 2 , participants on liraglutide 2.4/3.0 mg for the full 2 years ( pooled group , n=184 ) lost 3.0 kg ( 1.3–4.7 ) more weight than those on orlistat ( n=95 ; P<0.001 ) . Completers on liraglutide 2.4/3.0 mg ( n=92 ) maintained a 2-year weight loss of 7.8 kg from screening . With liraglutide 3.0 mg , 20-week body fat decreased by 15.4 % and lean tissue by 2.0 % . The most frequent drug-related side effects were mild to moderate , transient nausea and vomiting . With liraglutide 2.4/3.0 mg , the 2-year prevalence of prediabetes and metabolic syndrome decreased by 52 and 59 % , with improvements in blood pressure and lipids . Conclusion : Liraglutide is well tolerated , sustains weight loss over 2 years and improves cardiovascular risk factors 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 In the 2.8 years of the Diabetes Prevention Program ( DPP ) r and omised clinical trial , diabetes incidence in high-risk adults was reduced by 58 % with intensive lifestyle intervention and by 31 % with metformin , compared with placebo . We investigated the persistence of these effects in the long term . METHODS All active DPP participants were eligible for continued follow-up . 2766 of 3150 ( 88 % ) enrolled for a median additional follow-up of 5.7 years ( IQR 5.5 - 5.8 ) . 910 participants were from the lifestyle , 924 from the metformin , and 932 were from the original placebo groups . On the basis of the benefits from the intensive lifestyle intervention in the DPP , all three groups were offered group-implemented lifestyle intervention . Metformin treatment was continued in the original metformin group ( 850 mg twice daily as tolerated ) , with participants unmasked to assignment , and the original lifestyle intervention group was offered additional lifestyle support . The primary outcome was development of diabetes according to American Diabetes Association criteria . Analysis was by intention-to-treat . This study is registered with Clinical Trials.gov , number NCT00038727 . FINDINGS During the 10.0-year ( IQR 9.0 - 10.5 ) follow-up since r and omisation to DPP , the original lifestyle group lost , then partly regained weight . The modest weight loss with metformin was maintained . Diabetes incidence rates during the DPP were 4.8 cases per 100 person-years ( 95 % CI 4.1 - 5.7 ) in the intensive lifestyle intervention group , 7.8 ( 6.8 - 8.8 ) in the metformin group , and 11.0 ( 9.8 - 12.3 ) in the placebo group . Diabetes incidence rates in this follow-up study were similar between treatment groups : 5.9 per 100 person-years ( 5.1 - 6.8 ) for lifestyle , 4.9 ( 4.2 - 5.7 ) for metformin , and 5.6 ( 4.8 - 6.5 ) for placebo . Diabetes incidence in the 10 years since DPP r and omisation was reduced by 34 % ( 24 - 42 ) in the lifestyle group and 18 % ( 7 - 28 ) in the metformin group compared with placebo . INTERPRETATION During follow-up after DPP , incidences in the former placebo and metformin groups fell to equal those in the former lifestyle group , but the cumulative incidence of diabetes remained lowest in the lifestyle group . Prevention or delay of diabetes with lifestyle intervention or metformin can persist for at least 10 years . FUNDING National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK ) Aims /hypothesisLiraglutide can modulate insulin secretion by directly stimulating beta cells or indirectly through weight loss and enhanced insulin sensitivity . Recently , we showed that liraglutide treatment in overweight individuals with prediabetes ( impaired fasting glucose and /or impaired glucose tolerance ) led to greater weight loss ( −7.7 % vs −3.9 % ) and improvement in insulin resistance compared with placebo . The current study evaluates the effects on beta cell function of weight loss augmented by liraglutide compared with weight loss alone . Methods This was a parallel , r and omised study conducted in a single academic centre . Both participants and study administrators were blinded to treatment assignment . Individuals who were 40–70 years old , overweight ( BMI 27–40 kg/m2 ) and with prediabetes were r and omised ( via a computerised system ) to receive liraglutide ( n = 35 ) or matching placebo ( n = 33 ) , and 49 participants were analysed . All were instructed to follow an energy-restricted diet . Primary outcome was insulin secretory function , which was evaluated in response to grade d infusions of glucose and day-long mixed meals . Results Liraglutide treatment ( n = 24 ) significantly ( p ≤ 0.03 ) increased the insulin secretion rate ( % mean change [ 95 % CI ] ; 21 % [ 12 , 31 ] vs −4 % [ −11 , 3 ] ) and pancreatic beta cell sensitivity to intravenous glucose ( 229 % [ 161 , 276 ] vs −0.5 % ( −15 , 14 ] ) , and decreased insulin clearance rate ( −3.5 % [ −11 , 4 ] vs 8.2 [ 0.2 , 16 ] ) as compared with placebo ( n = 25 ) . The liraglutide-treated group also had significantly ( p ≤ 0.03 ) lower day-long glucose ( −8.2 % [ −11 , −6 ] vs −0.1 [ −3 , 2 ] ) and NEFA concentrations ( −14 [ −20 , −8 ] vs −2.1 [ −10 , 6 ] ) following mixed meals , whereas day-long insulin concentrations did not significantly differ as compared with placebo . In a multivariate regression analysis , weight loss was associated with a decrease in insulin secretion rate and day-long glucose and insulin concentrations in the placebo group ( p ≤ 0.05 ) , but there was no association with weight loss in the liraglutide group . The most common side effect of liraglutide was nausea . Conclusions /interpretationA direct stimulatory effect on beta cell function was the predominant change in liraglutide-augmented weight loss . These changes appear to be independent of weight loss . Trial registration Clinical Trials.gov NCT01784965 Funding The study was funded by the ADA OBJECTIVE The Restoring Insulin Secretion ( RISE ) Consortium is testing interventions design ed to preserve or improve β-cell function in prediabetes or early type 2 diabetes . RESEARCH DESIGN AND METHODS β-Cell function is measured using hyperglycemic clamps and oral glucose tolerance tests ( OGTTs ) . The adult medication protocol r and omizes participants to 12 months of placebo , metformin alone , liraglutide plus metformin , or insulin ( 3 months ) followed by metformin ( 9 months ) . The pediatric medication protocol r and omizes participants to metformin or insulin followed by metformin . The adult surgical protocol r and omizes participants to gastric b and ing or metformin ( 24 months ) . Adult medication protocol inclusion criteria include fasting plasma glucose 95–125 mg/dL ( 5.3–6.9 mmol/L ) , OGTT 2-h glucose ≥140 mg/dL ( ≥7.8 mmol/L ) , HbA1c 5.8–7.0 % ( 40–53 mmol/mol ) , and BMI 25–40 kg/m2 . Adult surgical protocol criteria are similar , except for fasting plasma glucose ≥90 mg/dL ( ≥5.0 mmol/L ) , BMI 30–40 kg/m2 , HbA1c < 7.0 % ( < 53 mmol/mol ) , and diabetes duration < 12 months . Pediatric inclusion criteria include fasting plasma glucose ≥90 mg/dL ( ≥5.0 mmol/L ) , 2-h glucose ≥140 mg/dL ( ≥7.8 mmol/L ) , HbA1c ≤8.0 % ( ≤64 mmol/mol ) , BMI > 85th percentile and ≤50 kg/m2 , 10–19 years of age , and diabetes < 6 months . RESULTS Primary outcomes are clamp-derived glucose-stimulated C-peptide secretion and maximal C-peptide response to arginine during hyperglycemia . Measurements are made at baseline , after 12 months on treatment , and 3 months after treatment withdrawal ( medication protocol s ) or 24 months postintervention ( surgery protocol ) . OGTT-derived measures are also obtained at these time points . CONCLUSIONS RISE is determining whether medication or surgical intervention strategies can mitigate progressive β-cell dysfunction in adults and youth with prediabetes or early type 2 diabetes CONTEXT As of 2005 , the International Committee of Medical Journal Editors required investigators to register their trials prior to participant enrollment as a precondition for publishing the trial 's findings in member journals . OBJECTIVE To assess the proportion of registered trials with results recently published in journals with high impact factors ; to compare the primary outcomes specified in trial registries with those reported in the published articles ; and to determine whether primary outcome reporting bias favored significant outcomes . DATA SOURCES AND STUDY SELECTION MEDLINE via PubMed was search ed for reports of r and omized controlled trials ( RCTs ) in 3 medical areas ( cardiology , rheumatology , and gastroenterology ) indexed in 2008 in the 10 general medical journals and specialty journals with the highest impact factors . DATA EXTRACTION For each included article , we obtained the trial registration information using a st and ardized data extraction form . RESULTS Of the 323 included trials , 147 ( 45.5 % ) were adequately registered ( ie , registered before the end of the trial , with the primary outcome clearly specified ) . Trial registration was lacking for 89 published reports ( 27.6 % ) , 45 trials ( 13.9 % ) were registered after the completion of the study , 39 ( 12 % ) were registered with no or an unclear description of the primary outcome , and 3 ( 0.9 % ) were registered after the completion of the study and had an unclear description of the primary outcome . Among articles with trials adequately registered , 31 % ( 46 of 147 ) showed some evidence of discrepancies between the outcomes registered and the outcomes published . The influence of these discrepancies could be assessed in only half of them and in these statistically significant results were favored in 82.6 % ( 19 of 23 ) . CONCLUSION Comparison of the primary outcomes of RCTs registered with their subsequent publication indicated that selective outcome reporting is prevalent Background Analysis of variance ( ANOVA ) , change-score analysis ( CSA ) and analysis of covariance ( ANCOVA ) respond differently to baseline imbalance in r and omized controlled trials . However , no empirical studies appear to have quantified the differential bias and precision of estimates derived from these methods of analysis , and their relative statistical power , in relation to combinations of levels of key trial characteristics . This simulation study therefore examined the relative bias , precision and statistical power of these three analyses using simulated trial data . Methods 126 hypothetical trial scenarios were evaluated ( 126 000 data sets ) , each with continuous data simulated by using a combination of levels of : treatment effect ; pretest-posttest correlation ; direction and magnitude of baseline imbalance . The bias , precision and power of each method of analysis were calculated for each scenario . Results Compared to the unbiased estimates produced by ANCOVA , both ANOVA and CSA are subject to bias , in relation to pretest-posttest correlation and the direction of baseline imbalance . Additionally , ANOVA and CSA are less precise than ANCOVA , especially when pretest-posttest correlation ≥ 0.3 . When groups are balanced at baseline , ANCOVA is at least as powerful as the other analyses . Apparently greater power of ANOVA and CSA at certain imbalances is achieved in respect of a biased treatment effect . Conclusions Across a range of correlations between pre- and post-treatment scores and at varying levels and direction of baseline imbalance , ANCOVA remains the optimum statistical method for the analysis of continuous outcomes in RCTs , in terms of bias , precision and statistical power BACKGROUND The frequency of obesity has risen dramatically in recent years but only few safe and effective drugs are currently available . We assessed the effect of liraglutide on bodyweight and tolerability in obese individuals without type 2 diabetes . METHODS We did a double-blind , placebo-controlled 20-week trial , with open-label orlistat comparator in 19 sites in Europe . 564 individuals ( 18 - 65 years of age , body-mass index 30 - 40 kg/m2 ) were r and omly assigned , with a telephone or web-based system , to one of four liraglutide doses ( 1.2 mg , 1.8 mg , 2.4 mg , or 3.0 mg , n=90 - 95 ) or to placebo ( n=98 ) administered once a day subcutaneously , or orlistat ( 120 mg , n=95 ) three times a day orally . All individuals had a 500 kcal per day energy-deficit diet and increased their physical activity throughout the trial , including the 2-week run-in . Weight change analysed by intention to treat was the primary endpoint . An 84-week open-label extension followed . This study is registered with Clinical Trials.gov , number NCT00422058 . FINDINGS Participants on liraglutide lost significantly more weight than did those on placebo ( p=0.003 for liraglutide 1.2 mg and p<0.0001 for liraglutide 1.8 - 3.0 mg ) and orlistat ( p=0.003 for liraglutide 2.4 mg and p<0.0001 for liraglutide 3.0 mg ) . Mean weight loss with liraglutide 1.2 - 3.0 mg was 4.8 kg , 5.5 kg , 6.3 kg , and 7.2 kg compared with 2.8 kg with placebo and 4.1 kg with orlistat , and was 2.1 kg ( 95 % CI 0.6 - 3.6 ) to 4.4 kg ( 2.9 - 6.0 ) greater than that with placebo . More individuals ( 76 % , n=70 ) lost more than 5 % weight with liraglutide 3.0 mg that with placebo ( 30 % , n=29 ) or orlistat ( 44 % , n=42 ) . Liraglutide reduced blood pressure at all doses , and reduced the prevalence of prediabetes ( 84 - 96 % reduction ) with 1.8 - 3.0 mg per day . Nausea and vomiting occurred more often in individuals on liraglutide than in those on placebo , but adverse events were mainly transient and rarely led to discontinuation of treatment . INTERPRETATION Liraglutide treatment over 20 weeks is well tolerated , induces weight loss , improves certain obesity-related risk factors , and reduces prediabetes . FUNDING Novo Nordisk A/S , Bagsvaerd , Denmark OBJECTIVE To investigate the effect of treatment with the glucagon-like peptide 1 receptor agonist exenatide on weight loss and metabolic parameters in obese nondiabetic women . RESEARCH DESIGN AND METHODS Forty-one obese women ( aged 48 ± 11 years and BMI 33.1 ± 4.1 kg/m2 ) participated in a 35-week r and omized , double-blind , placebo-controlled , crossover study , including two 16-week treatment periods separated by a 3-week washout period . There was no lifestyle intervention . The primary outcome was change in body weight . RESULTS Subjects treated with exenatide lost an average of 2.49 ± 0.66 kg compared with a 0.43 ± 0.63 kg weight gain during placebo treatment . Weight loss with exenatide treatment was noted at 2 weeks . The degree of weight loss could be stratified . A total of 30 % of subjects were high responders who lost ≥5 % body weight ( −7.96 ± 0.52 % ) , 39 % were moderate responders who lost < 5 % body weight ( −2.43 ± 0.45 % ) , and 31 % were nonresponders who gained weight ( 1.93 ± 0.53 % ) . Waist circumference also decreased significantly with exenatide treatment . Subjects experienced more nausea during exenatide treatment compared with placebo , but the severity decreased over time and did not correlate with weight loss . CONCLUSIONS Short-term exenatide treatment was associated with modest weight loss and decreased waist circumference in a cohort of obese nondiabetic women . A subset of individuals demonstrated robust weight loss that was detected very early in the course of treatment Background : Liraglutide 3.0 mg , with diet and exercise , produced substantial weight loss over 1 year that was sustained over 2 years in obese non-diabetic adults . Nausea was the most frequent side effect . Objective : To evaluate routinely collected data on nausea and vomiting among individuals on liraglutide and their influence on tolerability and body weight . Design : A r and omized , placebo-controlled , double-blind 20-week study with an 84-week extension ( sponsor unblinded at 20 weeks , open-label after 1 year ) in eight European countries ( Clinical trials.gov : NCT00422058).Subjects : After commencing a 500-kcal/day deficit diet plus exercise , 564 participants ( 18–65 years , body mass index ( BMI ) 30–40 kg m−2 ) were r and omly assigned ( after a 2-week run-in period ) to once-daily subcutaneous liraglutide ( 1.2 , 1.8 , 2.4 or 3.0 mg ) , placebo or open-label orlistat ( 120 mg × 3 per day ) . After 1 year , participants on liraglutide/placebo switched to liraglutide 2.4 mg , and subsequently , to liraglutide 3.0 mg ( based on 20-week and 1-year results , respectively ) . Results : The intention-to-treat population comprised 561 participants ( n=90–98 per arm , age 45.9±10.3 years , BMI 34.8±2.7 kg m−2 ( mean±s.d . ) ) . In year 1 , more participants reported ⩾1 episode of nausea/vomiting on treatment with liraglutide 1.2–3.0 mg ( 17–38 % ) than with placebo or orlistat ( both 4 % , P⩽0.001 ) . Most episodes occurred during dose escalation ( weeks 1–6 ) , with ‘ mild ’ or ‘ moderate ’ symptoms . Among participants on liraglutide 3.0 mg , 48 % reported some nausea and 13 % some vomiting , with considerable variation between countries , but only 4 out of 93 ( 4 % ) reported withdrawals . The mean 1-year weight loss on treatment with liraglutide 3.0 mg from r and omization was 9.2 kg for participants reporting nausea/vomiting episodes , versus 6.3 kg for those with none ( a treatment difference of 2.9 kg ( 95 % confidence interval 0.5–5.3 ) ; P=0.02 ) . Both weight losses were significantly greater than the respective weight losses for participants on placebo ( P<0.001 ) or orlistat ( P<0.05 ) . Quality -of-life scores at 20 weeks improved similarly with or without nausea/vomiting on treatment with liraglutide 3.0 mg . Conclusion : Transient nausea and vomiting on treatment with liraglutide 3.0 mg was associated with greater weight loss , although symptoms appeared tolerable and did not attenuate quality -of-life improvements . Improved data collection methods on nausea are warranted Obesity has a negative impact on health‐related quality of life ( HRQoL ) . The SCALE Obesity and Prediabetes study investigated the effect of liraglutide 3.0 mg , as adjunct to diet and exercise , on HRQoL in patients with obesity [ body mass index ( BMI ) ≥ 30 kg m−2 ] or overweight ( BMI ≥ 27 kg m−2 ) with comorbidity . Participants were advised on a 500 kcal d−1 deficit diet and a 150‐min week−1 exercise programme and were r and omised 2:1 to once‐daily subcutaneous liraglutide 3.0 mg or placebo . HRQoL was assessed using the Impact of Weight on Quality of Life‐Lite ( IWQOL‐Lite ) and Short‐Form 36 ( SF‐36 ) v2 health question naires . Individuals on liraglutide 3.0 mg ( n = 2046 ) had significantly greater improvements in IWQOL‐Lite total score ( 10.6 ± 13.3 ) vs. placebo ( n = 1020 ) ( 7.7 ± 12.8 ) and SF‐36 physical ( PCS ) and mental ( MCS ) component summary scores ( PCS , 3.6 ± 6.8 ; MCS , 0.2 ± 8.1 ) vs. placebo ( PCS , 2.2 ± 7.7 ; MCS , −0.9 ± 9.1 ) . The estimated treatment differences were IWQOL‐Lite total score 3.1 ( 95 % CI : 2.2 ; 4.0 ) , P < 0.0001 ; SF‐36 PCS 1.7 ( 95 % CI : 1.2 ; 2.2 ) , P < 0.0001 and MCS 0.9 ( 95 % CI : 0.3 ; 1.5 ) , P = 0.003 . All subscales of the IWQOL‐Lite and SF‐36 were significantly improved with liraglutide 3.0 mg vs. placebo . More patients on liraglutide 3.0 mg experienced meaningful improvement on the IWQOL‐Lite total ( P < 0.0001 ) and the SF‐36 PCS ( P < 0.0001 ) scores OBJECTIVE Agents that augment GLP-1 effects enhance glucose-dependent β-cell insulin production and secretion and thus are hoped to prevent progressive impairment in insulin secretion characteristic of type 2 diabetes ( T2D ) . The purpose of this study was to evaluate GLP-1 effects on β-cell secretory capacity , an in vivo measure of functional β-cell mass , early in the course of T2D . RESEARCH DESIGN AND METHODS We conducted a r and omized controlled trial in 40 subjects with early T2D who received the GLP-1 analog exenatide ( n = 14 ) , the dipeptidyl peptidase IV inhibitor sitagliptin ( n = 12 ) , or the sulfonylurea glimepiride ( n = 14 ) as an active comparator insulin secretagogue for 6 months . Acute insulin responses to arginine ( AIRarg ) were measured at baseline and after 6 months of treatment with 5 days of drug washout under fasting , 230 mg/dL ( glucose potentiation of arginine-induced insulin release [ AIRpot ] ) , and 340 mg/dL ( maximum arginine-induced insulin release [ AIRmax ] ) hyperglycemic clamp conditions , in which AIRmax provides the β-cell secretory capacity . RESULTS The change in AIRpot was significantly greater with glimepiride versus exenatide treatment ( P < 0.05 ) , and a similar trend was notable for the change in AIRmax ( P = 0.1 ) . Within each group , the primary outcome measure , AIRmax , was unchanged after 6 months of treatment with exenatide or sitagliptin compared with baseline but was increased with glimepiride ( P < 0.05 ) . α-Cell glucagon secretion ( AGRmin ) was also increased with glimepiride treatment ( P < 0.05 ) , and the change in AGRmin trended higher with glimepiride than with exenatide ( P = 0.06 ) . CONCLUSIONS After 6 months of treatment , exenatide or sitagliptin had no significant effect on functional β-cell mass as measured by β-cell secretory capacity , whereas glimepiride appeared to enhance β- and α-cell secretion Background : Obesity is strongly associated with prevalence of obstructive sleep apnea ( OSA ) , and weight loss has been shown to reduce disease severity . Objective : To investigate whether liraglutide 3.0 mg reduces OSA severity compared with placebo using the primary end point of change in apnea – hypopnea index ( AHI ) after 32 weeks . Liraglutide ’s weight loss efficacy was also examined . Subjects/ Methods : In this r and omized , double-blind trial , non-diabetic participants with obesity who had moderate ( AHI 15–29.9 events h−1 ) or severe ( AHI ⩾30 events h−1 ) OSA and were unwilling/unable to use continuous positive airway pressure therapy were r and omized for 32 weeks to liraglutide 3.0 mg ( n=180 ) or placebo ( n=179 ) , both as adjunct to diet ( 500 kcal day−1 deficit ) and exercise . Baseline characteristics were similar between groups ( mean age 48.5 years , males 71.9 % , AHI 49.2 events h−1 , severe OSA 67.1 % , body weight 117.6 kg , body mass index 39.1 kg m−2 , prediabetes 63.2 % , HbA1c 5.7 % ) . Results : After 32 weeks , the mean reduction in AHI was greater with liraglutide than with placebo ( −12.2 vs −6.1 events h−1 , estimated treatment difference : −6.1 events h−1 ( 95 % confidence interval ( CI ) , −11.0 to −1.2 ) , P=0.0150 ) . Liraglutide produced greater mean percentage weight loss compared with placebo ( −5.7 % vs −1.6 % , estimated treatment difference : −4.2 % ( 95 % CI , −5.2 to −3.1 % ) , P<0.0001 ) . A statistically significant association between the degree of weight loss and improvement in OSA end points ( P<0.01 , all ) was demonstrated post hoc . Greater reductions in glycated hemoglobin ( HbA1c ) and systolic blood pressure ( SBP ) were seen with liraglutide versus placebo ( both P<0.001 ) . The safety profile of liraglutide 3.0 mg was similar to that seen with doses ⩽1.8 mg . Conclusions : As an adjunct to diet and exercise , liraglutide 3.0 mg was generally well tolerated and produced significantly greater reductions than placebo in AHI , body weight , SBP and HbA1c in participants with obesity and moderate/severe OSA . The results confirm that weight loss improves OSA-related parameters Background Glucagon like peptide-1 ( GLP-1 ) receptor agonist treatment may improve endothelial function via direct and indirect mechanisms . We compared the acute and chronic effects of the GLP-1 receptor agonist exenatide vs. metformin on endothelial function in patients with obesity and pre-diabetes . Methods We performed a r and omized , open-label , clinical trial in 50 non-diabetic individuals ( mean age 58.5 ± 10.0 ; 38 females ) with abdominal obesity and either impaired fasting glucose , elevated HbA1c , or impaired glucose tolerance ( IGT ) who were r and omized to receive 3-months of exenatide or metformin . Microvascular endothelial function , assessed by digital reactive hyperemia ( reactive hyperemic index : RHI ) , C-reactive protein ( CRP ) , circulating oxidized LDL ( oxLDL ) , and vascular cell adhesion molecule-1 ( VCAM-1 ) were measured at baseline and 3-months . Seven subjects with IGT participated in a sub- study comparing the effects of pre-administration of exenatide and metformin on postpr and ial endothelial function . Results There were no differences for the change in RHI ( Δ exenatide : 0.01 ± 0.68 vs. Δ metformin : -0.17 ± 0.72 , P = 0.348 ) , CRP , oxLDL , or VCAM-1 between exenatide and metformin treatment . Triglycerides were reduced more with exenatide compared to metformin ( Δ exenatide : -25.5 ± 45.7 mg/dL vs. Δ metformin : -2.9 ± 22.8 mg/dL , P = 0.032 ) . In the sub- study , there was no difference in postpr and ial RHI between exenatide and metformin . Conclusions Three months of exenatide therapy had similar effects on microvascular endothelial function , markers of inflammation , oxidative stress , and vascular activation , as metformin , in patients with obesity and pre-diabetes . Clinical trials registration This study is registered on http://www . clinical In recent years , the use of the last observation carried forward ( LOCF ) approach in imputing missing data in clinical trials has been greatly criticized , and several likelihood-based modeling approaches are proposed to analyze such incomplete data . One of the proposed likelihood-based methods is the Mixed-Effect Model Repeated Measure ( MMRM ) model . To compare the performance of LOCF and MMRM approaches in analyzing incomplete data , two extensive simulation studies are conducted , and the empirical bias and Type I error rates associated with estimators and tests of treatment effects under three missing data paradigms are evaluated . The simulation studies demonstrate that LOCF analysis can lead to substantial biases in estimators of treatment effects and can greatly inflate Type I error rates of the statistical tests , whereas MMRM analysis on the available data leads to estimators with comparatively small bias , and controls Type I error rates at a nominal level in the presence of missing completely at r and om ( MCAR ) or missing at r and om ( MAR ) and some possibility of missing not at r and om ( MNAR ) data . In a sensitivity analysis of 48 clinical trial data sets obtained from 25 New Drug Applications ( NDA ) su bmi ssions of neurological and psychiatric drug products , MMRM analysis appears to be a superior approach in controlling Type I error rates and minimizing biases , as compared to LOCF ANCOVA analysis . In the exploratory analyses of the data sets , no clear evidence of the presence of MNAR missingness is found Background The grading of recommendation , assessment , development and evaluation ( GRADE ) approach is widely implemented in health technology assessment and guideline development organisations throughout the world . GRADE provides a transparent approach to reaching judgements about the quality of evidence on the effects of a health care intervention , but is complex and therefore challenging to apply in a consistent manner . Methods We developed a checklist to guide the research er to extract the data required to make a GRADE assessment . We applied the checklist to 29 meta-analyses of r and omised controlled trials on the effectiveness of health care interventions . Two review ers used the checklist for each paper and used these data to rate the quality of evidence for a particular outcome . Results For most ( 70 % ) checklist items , there was good agreement between review ers . The main problems were for items relating to indirectness where considerable judgement is required . Conclusions There was consistent agreement between review ers on most items in the checklist . The use of this checklist may be an aid to improving the consistency and reproducibility of GRADE assessment s , particularly for inexperienced users or in rapid review s without the re sources to conduct assessment s by two research ers independently CONTEXT HIV infection is associated with a greater risk for fasting hyperinsulinemia , impaired glucose tolerance , and higher incidence rates for vascular disease , myocardial infa rct ion , or stroke despite effective combination antiretroviral therapy ( cART ) . The underlying mechanism(s ) may involve chronic low- grade systemic inflammation and immune cell activation . Dipeptidyl peptidase-4 inhibitors ( sitagliptin ) improve glucose tolerance and may possess immunomodulatory effects because leukocyte CD26 cell surface receptors express dipeptidyl peptidase-4 activity . OBJECTIVE Sitagliptin will reduce inflammatory and immune cell activation markers known to be elevated in cART-treated HIV-infected ( HIV+ ) adults with impaired glucose tolerance . DESIGN This was design ed as a prospect i ve , r and omized , placebo-controlled , double-blind trial of sitagliptin in HIV+ adults . SETTING The setting was an academic medical center . PATIENTS Patients were cART-treated HIV+ men and women ( n = 36 ) with stable HIV disease and impaired glucose tolerance . INTERVENTIONS Interventions included sitagliptin 100 mg/d or placebo for 8 weeks . MAIN OUTCOME MEASURES At baseline and week 8 , plasma high-sensitivity C-reactive protein and C-X-C motif chemokine 10 concentrations ( ELISA ) , oral glucose tolerance , and abdominal sc adipose mRNA expression for M1 macrophage markers ( monocyte chemotactic protein-1 , EGF-like module-containing , mucin-like hormone receptor 1 ) . RESULTS Sitagliptin reduced glucose area under the curve ( P = .002 ) and improved oral glucose insulin sensitivity index ( P = .04 ) more than placebo . Sitagliptin reduced plasma high-sensitivity C-reactive protein and C-X-C motif chemokine 10 levels more than placebo ( P < .009 ) . Adipose tissue monocyte chemotactic protein-1 mRNA abundance declined significantly more ( P = .01 ) , and adipose EGF-like module-containing , mucin-like hormone receptor 1 mRNA expression tended to decline more ( P = .19 ) in sitagliptin than placebo . CONCLUSION Sitagliptin had beneficial systemic and adipose anti-inflammatory effects in cART-treated HIV+ adults with impaired glucose tolerance . Large-scale , long-term studies should determine whether sitagliptin reduces cardiovascular risk and events in HIV+ adults Background : Positive predictive value ( PPV ) of hemoglobin A1c ( HbA1c ) for diagnosis of prediabetes in clinical practice has not been well studied . Methods : In a prospect i ve study , patients diagnosed with prediabetes based on HbA1c ( 5.7%–6.4 % ) underwent a 75-g oral glucose tolerance test ( OGTT ) as the gold st and ard test to diagnose dysglycemia . Demographics , anthropometrics , comorbidity , concomitant prescription medications and biochemical data were collected . Results : We identified 66 patients with HbA1c-based prediabetes with a mean HbA1c of 6.00 ± 0.20 % . However , based on the OGTT , 32 had normal glucose tolerance ( NGT ) , 26 had prediabetes and 8 had diabetes yielding a PPV of HbA1c of 39.4 % . In univariate analysis , the patients with the OGTT-based prediabetes administered more medications for associated medical problems compared with the NGT group ( 5.9 ± 2.2 versus 2.6 ± 1.8 , P < 0.0001 ) . After adjustment for baseline variables , the medication use remained significantly different between OGTT-based prediabetes and NGT groups ( P = 0.041 ) . Conclusions : PPV of HbA1c for diagnosis of prediabetes in clinical setting is low . Patients with HbA1c of 5.7 % to 6.4 % should undergo OGTT to confirm diagnosis of dysglycemia 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 Chronic exenatide treatment in type 2 diabetes is associated with improved glucose control and fasting lipid levels , as well as weight loss . Less established is whether exenatide directly reduces postpr and ial lipid and lipoprotein levels without the reduction in body weight or fasting glucose and triglycerides levels that frequently occur with prolonged therapy . Therefore , the effect of a single injection of exenatide on postpr and ial lipids , remnant lipoproteins , and apolipoproteins was studied . METHODS A double-blinded , r and omized , placebo-controlled , crossover study was conducted in 35 subjects ( 31 men and 4 women ) with impaired glucose tolerance ( n=20 ) or recent onset type 2 diabetes ( n=15 ) . A single subcutaneous injection of exenatide ( 10 microg ) or normal saline was administered just prior to a high-calorie , fat-enriched breakfast meal . Concentrations of triglycerides ( TG ) , apolipoproteins B-48 and CIII , non-esterified fatty acids ( NEFA ) , and remnant lipoprotein ( RLP ) cholesterol and TG in serum or plasma were measured prior to the injection and for up to 8 h postpr and ially . RESULTS Exenatide markedly reduced postpr and ial elevation of TG , apolipoproteins B-48 and CIII , RLP-cholesterol and RLP-triglyceride ( all p<0.001 ) . Postpr and ial declines in NEFA were less pronounced but persisted longer with exenatide compared to placebo ( p<0.05 ) . These effects of exenatide were not affected either by glucose tolerance status or by treatment with statins . CONCLUSION These results demonstrate that exenatide acutely and profoundly inhibits postpr and ial excursions of proatherogenic lipids and lipoproteins and may offer additional cardiovascular risk reduction ( NCT00974272 ) BACKGROUND Newly detected impaired glucose tolerance ( IGT ) or type 2 diabetes mellitus ( T2DM ) are common in patients with acute coronary syndrome ( ACS ; i.e. unstable angina/myocardial infa rct ion ) and related to disturbed beta-cell function . The aim of this study is to test the hypothesis that treatment with a dipeptidyl peptidase-4 inhibitor initiated soon after a coronary event improves beta-cell function . METHODS Acute coronary syndrome ACS patients with IGT or T2DM ( n = 71 ) , screened by oral glucose tolerance test ( OGTT ) 4 - 23 days ( median 6 days ) after hospital admission , were r and omly assigned to sitagliptin 100 mg ( n = 34 ) or placebo ( n = 37 ) and treated for a duration of 12 weeks . All patients received lifestyle advice but no glucose-lowering agents other than the study drug . The study end-point was beta-cell function assessed using the insulinogenic index ( IGI = ΔInsulin30 /ΔGlucose30 ) , derived from an OGTT , and acute insulin response to glucose ( AIRg ) assessed by a frequently sample d intravenous glucose tolerance test . RESULTS The IGI and AIRg did not differ at baseline between the sitagliptin and placebo groups ( 69.9 vs. 66.4 pmol mmol(-1 ) and 1394 vs. 1106 pmol L(-1 ) min(-1 ) respectively ) . After 12 weeks , the IGI was 85.0 in the sitagliptin and 58.1 pmol/mmol in the placebo group ( P = 0.013 ) and AIRg was 1909 and 1043 pmol L(-1 ) min(-1 ) ( P < 0.0001 ) in the sitagliptin and placebo groups respectively . Fasting glucose at baseline was 6.1 mmol L(-1 ) in sitagliptin-treated patients and 6.0 mmol L(-1 ) in those who received placebo compared with 5.8 and 5.9 mmol L(-1 ) respectively , after 12 weeks of treatment . Post load glucose metabolism improved in significantly more sitagliptin-treated patients compared with the placebo group ( P = 0.003 ) . Sitagliptin was well tolerated . CONCLUSION Sitagliptin improved beta-cell function and glucose perturbations in patients with ACS and newly diagnosed glucose disturbances A key component of the Cochrane Collaboration 's risk of bias tool for critically evaluating r and omised trials is the consideration of whether baseline characteristics of the treatment groups being compared are systematic ally different . Considered under the domain of ' selection bias ' , this is currently evaluated by looking at the methods of r and omisation and specifically at the generation of the r and omised allocation sequence and the concealment of this sequence during the process of r and omisation . Assessment of the actual similarity of baseline variables across groups in demographic and clinical characteristics is seldom performed . Even when performed , the link with selection bias is sometimes not considered . Methods of r and omisation and allocation concealment are often poorly reported in published trials , yet baseline data tables are presented in a large majority of trial reports . In this article , we propose that assessment of trial baseline data should form a key and prominent part of selection bias judgements when using the risk of bias tool . We outline the possible benefits from using this approach , including reduced uncertainty in systematic review conclusions , reduced risk of chance findings being ascribed to treatment effects and better use of available evidence by a more considered approach to evaluating studies using imperfect r and omisation and allocation methods BACKGROUND The EXAMINE trial showed non-inferiority of the DPP-4 inhibitor alogliptin to placebo on major adverse cardiac event ( MACE ) rates in patients with type 2 diabetes and recent acute coronary syndromes . Concerns about excessive rates of in-hospital heart failure in another DPP-4 inhibitor trial have been reported . We therefore assessed hospital admission for heart failure in the EXAMINE trial . METHODS Patients with type 2 diabetes and an acute coronary syndrome event in the previous 15 - 90 days were r and omly assigned alogliptin or placebo plus st and ard treatment for diabetes and cardiovascular disease prevention . The prespecified exploratory extended MACE endpoint was all-cause mortality , non-fatal myocardial infa rct ion , non-fatal stroke , urgent revascularisation due to unstable angina , and hospital admission for heart failure . The post-hoc analyses were of cardiovascular death and hospital admission for heart failure , assessed by history of heart failure and brain natriuretic peptide ( BNP ) concentration at baseline . We also assessed changes in N-terminal pro-BNP ( NT-pro-BNP ) from baseline to 6 months . This study is registered with Clinical Trials.gov , number NCT00968708 . FINDINGS 5380 patients were assigned to alogliptin ( n=2701 ) or placebo ( n=2679 ) and followed up for a median of 533 days ( IQR 280 - 751 ) . The exploratory extended MACE endpoint was seen in 433 ( 16·0 % ) patients assigned to alogliptin and in 441 ( 16·5 % ) assigned to placebo ( hazard ratio [ HR ] 0·98 , 95 % CI 0·86 - 1·12 ) . Hospital admission for heart failure was the first event in 85 ( 3·1 % ) patients taking alogliptin compared with 79 ( 2·9 % ) taking placebo ( HR 1·07 , 95 % CI 0·79 - 1·46 ) . Alogliptin had no effect on composite events of cardiovascular death and hospital admission for heart failure in the post hoc analysis ( HR 1·00 , 95 % CI 0·82 - 1·21 ) and results did not differ by baseline BNP concentration . NT-pro-BNP concentrations decreased significantly and similarly in the two groups . INTERPRETATION In patients with type 2 diabetes and recent acute coronary syndromes , alogliptin did not increase the risk of heart failure outcomes . FUNDING Takeda Development Center Americas BACKGROUND Obesity is a chronic disease with serious health consequences , but weight loss is difficult to maintain through lifestyle intervention alone . Liraglutide , a glucagon-like peptide-1 analogue , has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg , injected subcutaneously . METHODS We conducted a 56-week , double-blind trial involving 3731 patients who did not have type 2 diabetes and who had a body-mass index ( BMI ; the weight in kilograms divided by the square of the height in meters ) of at least 30 or a BMI of at least 27 if they had treated or untreated dyslipidemia or hypertension . We r and omly assigned patients in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide at a dose of 3.0 mg ( 2487 patients ) or placebo ( 1244 patients ) ; both groups received counseling on lifestyle modification . The co primary end points were the change in body weight and the proportions of patients losing at least 5 % and more than 10 % of their initial body weight . RESULTS At baseline , the mean ( ±SD ) age of the patients was 45.1±12.0 years , the mean weight was 106.2±21.4 kg , and the mean BMI was 38.3±6.4 ; a total of 78.5 % of the patients were women and 61.2 % had prediabetes . At week 56 , patients in the liraglutide group had lost a mean of 8.4±7.3 kg of body weight , and those in the placebo group had lost a mean of 2.8±6.5 kg ( a difference of -5.6 kg ; 95 % confidence interval , -6.0 to -5.1 ; P<0.001 , with last-observation-carried-forward imputation ) . A total of 63.2 % of the patients in the liraglutide group as compared with 27.1 % in the placebo group lost at least 5 % of their body weight ( P<0.001 ) , and 33.1 % and 10.6 % , respectively , lost more than 10 % of their body weight ( P<0.001 ) . The most frequently reported adverse events with liraglutide were mild or moderate nausea and diarrhea . Serious events occurred in 6.2 % of the patients in the liraglutide group and in 5.0 % of the patients in the placebo group . CONCLUSIONS In this study , 3.0 mg of liraglutide , as an adjunct to diet and exercise , was associated with reduced body weight and improved metabolic control . ( Funded by Novo Nordisk ; SCALE Obesity and Prediabetes NN8022 - 1839 Clinical Trials.gov number , NCT01272219 . ) 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 OBJECTIVE The ability to accurately identify articles about therapy in large bibliographic data bases such as EMBASE is important for research ers and clinicians . Our study aim ed to develop optimal search strategies for detecting sound treatment studies in EMBASE in the year 2000 . METHODS H and search es of journals were compared with retrievals from EMBASE for c and i date search strategies . Six trained research assistants review ed fifty-five journals indexed in EMBASE and rated articles using purpose and quality indicators . C and i date search strategies were developed for identifying treatment articles and then tested , and the retrievals were compared with the h and - search data . The operating characteristics of the strategies were calculated . RESULTS Three thous and eight hundred fifty articles were original studies on treatment , of which 1,256 ( 32.6 % ) were method ologically sound . Combining search terms revealed a top performing strategy ( r and om:.tw . OR clinical trial:.mp . OR exp health care quality ) with sensitivity of 98.9 % and specificity of 72.0 % . Maximizing specificity , a top performing strategy ( double-blind:.mp . OR placebo:.tw . OR blind : .tw . ) achieved a value over 96.0 % , but with compromised sensitivity at 51.7 % . A 3-term strategy achieved the best optimization of sensitivity and specificity ( r and om:.tw . OR placebo:.mp . OR double-blind:.tw . ) , with both these values over 92.0 % . CONCLUSION Search strategies can achieve high performance for retrieving sound treatment studies in EMBASE Liraglutide 3.0 mg , an acylated GLP‐1 analogue approved for weight management , lowers body weight through decreased energy intake . We conducted exposure‐response analyses to provide important information on individual responses to given drug doses , reflecting inter‐individual variations in drug metabolism , absorption and excretion Background The high prevalence and incidence of type 2 diabetes mellitus ( DM ) , and its associated morbidity and mortality , has prompted growing international interest and effort in the primary prevention of this disease . Primary prevention is possible since type 2 DM is preceded by prediabetes , offering a window opportunity to treat patients , and prevent the emergence of advanced disease . Sitagliptin is an oral dipeptidyl peptidase-IV inhibitor that preserves existing beta cell function and increases beta cell mass . These two effects have been demonstrated both in vitro and in animal studies , and current clinical data show that sitagliptin is safe . Metformin , a biguanide , reduces insulin resistance and inhibits hepatic gluconeogenesis , and has an excellent safety profile . The combination of metformin and sitagliptin , targeting both characteristics of prediabetes ( insulin resistance and progressive beta cell degeneration ) , may potentially slow or halt the progression from prediabetes to type 2 DM . This paper describes the rationale and design of the Sitagliptin and Metformin in PreDiabetes ( SiMePreD ) study . Objective The aim of this study is to determine the effect of sitagliptin and metformin on progression from prediabetes to type 2 DM . The objectives of the study are to determine the effects of metformin and placebo on glycemic endpoints , the effects of sitagliptin and metformin on glycemic endpoints , the effects of metformin and placebo on incidence of cardiovascular disease and death , and the effects of sitagliptin and metformin on incidence of cardiovascular disease and death . Methods This is a r and omized , double-blind , multicenter clinical study that will determine if the combination of metformin and sitagliptin is effective in preventing the progression from prediabetes to type 2 DM . The study will contain two arms ( metformin/sitagliptin and metformin/placebo ) . Primary endpoints include the number of subjects progressing from prediabetes to type 2 DM , the number of cardiovascular events , and the number of deaths . The planned duration of the study is five years , and 410 subjects will be included in each group . Data analyses will include clinical ly relevant measures ( eg , numbers needed to treat and numbers needed to harm ) and will be performed according to the intention-to-treat principle . Results This study is currently in the process of acquiring research funding . Conclusions The SiMePreD study is the first study to investigate the utility of sitagliptin in combination with metformin for the primary prevention of type 2 DM Sitagliptin has been widely used for the treatment of diabetes and shown recently to have beneficial pleiotropic outcomes on cardiovascular systems in experimental studies . However , little is known about the influence of sitagliptin on atherosclerosis-related cardiovascular diseases in a clinical setting . This study examined the effect of sitagliptin on carotid intima-media thickness ( IMT ) . A total of 76 patients with clinical ly stable and documented coronary artery disease , who were newly diagnosed with impaired glucose tolerance or mild type 2 diabetes mellitus , were allocated , r and omly , to receive either sitagliptin 100 mg/day or the placebo control . Common carotid IMT , glucose profiles , glycosylated hemoglobin ( HbA1c ) , and lipid profiles were measured at baseline and repeated at 12 months . Sitagliptin-treated patients showed less IMT progression than the control group ( p = 0.02 ) . In addition , the sitagliptin group showed greater reductions in body weight ( 2.2 % ) , 2-hour glucose levels on the 75-g oral glucose tolerance test ( 17.3 % ) , HbA1c ( 4.7 % ) , and low-density lipoprotein cholesterol levels ( 7.9 % ) from that at baseline . In conclusion , treatment with sitagliptin for 12 months was associated with a beneficial effect in the prevention of carotid IMT progression , compared with the diet control BACKGROUND Impaired glucose tolerance is associated with increased rates of cardiovascular disease and conversion to type 2 diabetes mellitus . Interventions that may prevent or delay such occurrences are of great clinical importance . METHODS We conducted a r and omized , double-blind , placebo-controlled study to examine whether pioglitazone can reduce the risk of type 2 diabetes mellitus in adults with impaired glucose tolerance . A total of 602 patients were r and omly assigned to receive pioglitazone or placebo . The median follow-up period was 2.4 years . Fasting glucose was measured quarterly , and oral glucose tolerance tests were performed annually . Conversion to diabetes was confirmed on the basis of the results of repeat testing . RESULTS Annual incidence rates for type 2 diabetes mellitus were 2.1 % in the pioglitazone group and 7.6 % in the placebo group , and the hazard ratio for conversion to diabetes in the pioglitazone group was 0.28 ( 95 % confidence interval , 0.16 to 0.49 ; P<0.001 ) . Conversion to normal glucose tolerance occurred in 48 % of the patients in the pioglitazone group and 28 % of those in the placebo group ( P<0.001 ) . Treatment with pioglitazone as compared with placebo was associated with significantly reduced levels of fasting glucose ( a decrease of 11.7 mg per deciliter vs. 8.1 mg per deciliter [ 0.7 mmol per liter vs. 0.5 mmol per liter ] , P<0.001 ) , 2-hour glucose ( a decrease of 30.5 mg per deciliter vs. 15.6 mg per deciliter [ 1.6 mmol per liter vs. 0.9 mmol per liter ] , P<0.001 ) , and HbA(1c ) ( a decrease of 0.04 percentage points vs. an increase of 0.20 percentage points , P<0.001 ) . Pioglitazone therapy was also associated with a decrease in diastolic blood pressure ( by 2.0 mm Hg vs. 0.0 mm Hg , P=0.03 ) , a reduced rate of carotid intima-media thickening ( 31.5 % , P=0.047 ) , and a greater increase in the level of high-density lipoprotein cholesterol ( by 7.35 mg per deciliter vs. 4.5 mg per deciliter [ 0.4 mmol per liter vs. 0.3 mmol per liter ] , P=0.008 ) . Weight gain was greater with pioglitazone than with placebo ( 3.9 kg vs. 0.77 kg , P<0.001 ) , and edema was more frequent ( 12.9 % vs. 6.4 % , P=0.007 ) . CONCLUSIONS As compared with placebo , pioglitazone reduced the risk of conversion of impaired glucose tolerance to type 2 diabetes mellitus by 72 % but was associated with significant weight gain and edema . ( Funded by Takeda Pharmaceuticals and others ; Clinical Trials.gov number , NCT00220961 . ) BACKGROUND Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial , one of four trials in the SCALE programme . In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aim ed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes . METHODS In this r and omised , double-blind , placebo-controlled trial , adults with prediabetes and a body-mass index of at least 30 kg/m2 , or at least 27 kg/m2 with comorbidities , were r and omised 2:1 , using a telephone or web-based system , to once-daily subcutaneous liraglutide 3·0 mg or matched placebo , as an adjunct to a reduced-calorie diet and increased physical activity . Time to diabetes onset by 160 weeks was the primary outcome , evaluated in all r and omised treated individuals with at least one post-baseline assessment . The trial was conducted at 191 clinical research sites in 27 countries and is registered with Clinical Trials.gov , number NCT01272219 . FINDINGS The study ran between June 1 , 2011 , and March 2 , 2015 . We r and omly assigned 2254 patients to receive liraglutide ( n=1505 ) or placebo ( n=749 ) . 1128 ( 50 % ) participants completed the study up to week 160 , after withdrawal of 714 ( 47 % ) participants in the liraglutide group and 412 ( 55 % ) participants in the placebo group . By week 160 , 26 ( 2 % ) of 1472 individuals in the liraglutide group versus 46 ( 6 % ) of 738 in the placebo group were diagnosed with diabetes while on treatment . The mean time from r and omisation to diagnosis was 99 ( SD 47 ) weeks for the 26 individuals in the liraglutide group versus 87 ( 47 ) weeks for the 46 individuals in the placebo group . Taking the different diagnosis frequencies between the treatment groups into account , the time to onset of diabetes over 160 weeks among all r and omised individuals was 2·7 times longer with liraglutide than with placebo ( 95 % CI 1·9 to 3·9 , p<0·0001 ) , corresponding with a hazard ratio of 0·21 ( 95 % CI 0·13 - 0·34 ) . Liraglutide induced greater weight loss than placebo at week 160 ( -6·1 [ SD 7·3 ] vs -1·9 % [ 6·3 ] ; estimated treatment difference -4·3 % , 95 % CI -4·9 to -3·7 , p<0·0001 ) . Serious adverse events were reported by 227 ( 15 % ) of 1501 r and omised treated individuals in the liraglutide group versus 96 ( 13 % ) of 747 individuals in the placebo group . INTERPRETATION In this trial , we provide results for 3 years of treatment , with the limitation that withdrawn individuals were not followed up after discontinuation . Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes . FUNDING Novo Nordisk , Denmark |
12,968 | 28,816,931 | Studies examining the effects of combined training methods in postmenopausal and older women showed contrasting results , possibly due to the wide range of the participants ’ age , the evaluation of different regions , and the varying characteristics of the training methods between studies .
Overall , it appears that exercise modes that combine resistance , weight-bearing training , and impact-aerobic activities can increase or prevent muscle and skeletal mass loss during the ageing process in women . | Objective : The purpose of this systematic review was to up date and examine to what extent multicomponent training interventions could improve lean and bone mass at different anatomical regions of the body in postmenopausal and older women . | To assess age and gender differences in muscle strength , isometric , concentric ( Con ) , and eccentric ( Ecc ) peak torque was measured in the knee extensors at a slow ( 0.52 rad/s ) and fast ( 3.14 rad/s ) velocity in 654 subjects ( 346 men and 308 women , aged 20 - 93 yr ) from the Baltimore Longitudinal Study of Aging . Regression analysis revealed significant ( P < 0.001 ) age-related reductions in Con and Ecc peak torque for men and women at both velocities , but no differences were observed between the gender groups or velocities . Age explained losses in Con better than Ecc peak torque , accounting for 30 % ( Con ) vs. 19 % ( Ecc ) of the variance in men and 28 % ( Con ) vs. 11 % ( Ecc ) in women . To assess age and gender differences in the ability to store and utilize elastic energy , the stretch-shortening cycle was determined in a subset of subjects ( n = 47 ) . The older women ( mean age = 70 yr ) showed a significantly greater enhancement in the stretch-shortening cycle , compared with men of similar age ( P < 0.01 ) and compared with younger men and women ( each P < 0.05 ) . Both men and women showed significant declines in muscle quality for Con peak torque ( P < 0.01 ) , but no gender differences were observed . Only the men showed a significant decline in muscle quality ( P < 0.001 ) for Ecc peak torque . Thus both men and women experience age-related losses in isometric , Con , and Ecc knee extensor peak torque ; however , age accounted for less of the variance in Ecc peak torque in women , and women tend to better preserve muscle quality with age for Ecc peak torque . In addition , older women have an enhanced capacity to store and utilize elastic energy compared with similarly aged men as well as with younger women and men The purpose s of this study were to analyze the impact of 24 weeks of vibratory and multicomponent training ( MT ) and to determine what type of training creates greater adaptations on body composition and isokinetic strength of the knee and ankle joints in postmenopausal women . Thirty-eight women ( 60.0 ± 6.3 years ) were r and omly assigned to whole body vibration group ( WBVG ) , multicomponent training group ( MTG ) , or a control group . A significant decrease in total fat mass was observed in experimental groups . There were no changes in total lean mass and total bone mineral density in both groups . WBVG and MTG showed significant increases in isokinetic strength for knee extensors at 60 ° /s and at 270 ° /s . Regarding the ankle joint , there were significant increments in strength for plantar flexion at 60 ° /s in WBVG and at 120 ° /s in the two trainings groups . MTG showed a significant increase in strength for dorsiflexion at 60 ° /s . With respect to eversion and inversion , WBVG and MTG improved strength at 60 ° /s . Also , the WBVG showed increased strength in the ankle evertors at 120 ° /s and both groups showed increased strength in the ankle invertors at 120 ° /s . Twenty-four weeks of whole body vibration or MTs result in positive modifications in total fat mass . These trainings are effective in improving knee extension and stabilizer muscles of the ankle joint strength Forty-eight community living women 66–87 years old volunteered to participate in a 12-month prospect i ve , r and omized , controlled , trial . The aim was to determine if a combined weight-bearing training program twice a week would be beneficial to bone mineral density and neuromuscular function . The participants were pairwise age-matched and r and omly assigned to either an exercise group ( n=24 ) or a control group ( n=24 ) . Twenty-one subjects in the intervention group and 19 in the control group completed the study . The exercise program lasted for 50 min and consisted of a combination of strengthening , aerobic , balance and coordination exercises . The mean percentage of scheduled sessions attended for the exercise group was 67 % . At the completion of the study , the intervention group showed significant increments in bone mineral density of the Ward ’s triangle ( 8.4 % , P<0.01 ) as well as improvement in maximum walking speed ( 11.4 % , P<0.001 ) and isometric grip strength ( 9.9 % , P<0.05 ) , as compared to the control group . The conclusion was that a combined weight-bearing training program might reduce fracture risk factors by improving bone density as well as muscle strength and walking ability . This program could be suitable for older community living women in general , and might , therefore , have important implication s for fracture prevention Summary We determined the effect of antioxidants and resistance training on bone mineral density of postmenopausal women . After 6 months , we observed a significant decrease in the lumbar spine BMD of the placebo group while other groups remained stable . Antioxidants may offer protection against bone loss such as resistance training . Introduction The purpose of this pilot study was to determine the effects of antioxidant supplements combined to resistance training on bone mineral density ( BMD ) in healthy elderly women . Methods Thirty-four postmenopausal women ( 66.1 ± 3.3 years ) were r and omized in four groups ( placebo , n = 7 ; antioxidants , n = 8 ; exercise and placebo , n = 11 ; and exercise and antioxidants , n = 8) . The 6-month intervention consisted in antioxidant supplements ( 600 mg vitamin E and 1,000 mg vitamin C daily ) or resistance exercise ( 3 × /week ) . Femoral neck and lumbar spine BMD ( DXA ) and dietary intakes ( 3-day food record ) were measured before and after the intervention . A repeated measure ANOVA and non-parametric Mann – Whitney U tests were used . Results We observed a significant decrease in the placebo group for lumbar spine BMD ( pre , 1.01 ± 0.17 g/cm2 ; post , 1.00 ± 0.16 g/cm2 ; P < 0.05 respectively ) while it remained stable in all other groups . No changes were observed for femoral neck BMD . Conclusions Antioxidant vitamins may offer some protection against bone loss in the same extent as resistance exercise although combining both does not seem to produce additional effects . Our results suggest to further investigate the impact of antioxidant supplements on the prevention of osteoporosis Summary This study showed that combination of strength , balance , agility and jumping training prevented functional decline and bone fragility in home-dwelling elderly women . The finding supports the idea that it is possible to maintain good physical functioning by multi-component exercise program and thus postpone the age-related functional problems . Introduction This 1-year r and omized , controlled exercise intervention trial assessed the effects of two different training programs and their combination on physical functioning and bone in home-dwelling elderly women . Methods One hundred and forty-nine healthy women aged 70–78 years were r and omly assigned into : group 1—resistance training ( RES ) , group 2—balance-jumping training ( BAL ) , group 3—combination of resistance and balance-jumping training ( COMB ) , and group 4—controls ( CON ) . Self-rated physical functioning , leg extensor force , dynamic balance , and bone mass and structure were measured . Results Self-rated physical functioning improved in the COMB group , but was reduced in the CON group ; the mean inter-group difference was 10 % ( 95 % CI : 0–22 % ) . Mean increase in the leg extensor force was higher in the RES ( 14 % ; 4–25 % ) and COMB ( 13 % ; 3–25 % ) compared with the CON groups . Dynamic balance improved in the BAL ( 6 % ; 1–11 % ) and in the COMB ( 8 % ; 3–12 % ) groups . There were no inter-group differences in BMC at the proximal femur . In those COMB women who trained at least twice a week , the tibial shaft structure weakened 2 % ( 0–4 % ) less than those in the CON group . Conclusions Strength , balance , agility , and jumping training ( especially in combination ) prevented functional decline in home-dwelling elderly women . In addition , positive effects seen in the structure of the loaded tibia indicated that exercise may also play a role in preventing bone fragility 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 This study examined the correlations between isokinetic muscle strength of knee and elbow flexors and extensors with vertebral and femoral bone mineral density in a population of 106 women between the ages of 44 and 87 years . The absolute value of muscle strength correlated significantly with bone mineral density ; muscle strength of the upper limb appeared to be more closely correlated with bone mass , while muscle strength in the lower limb was more specific for femoral mineral bone density . The most important finding that these results demonstrated was a concomitant decline in muscle strength of the upper limb and bone mineral density between the 5th and 6th decades . In contrast , they also showed a decline in muscle strength of the lower limbs after the 6th decade , occurring before the decline in bone mineral density observed between the 7th and 8th decades . From these results it would appear that other studies are required to examine the relationship between the essentially hormonal role in postmenopausal decline in muscle strength and the decline in physical activity during the senile period . These elements are important because they must be taken into account in physical exercise programmes design ed to prevent osteoporosis UNLABELLED We prospect ively examined vBMD and structural bone parameters assessed by QCT among participants of the InCHIANTI study over a 6-yr follow-up . Periosteal apposition occurred both in men and women . Endocortical resorption causes bone loss in older women despite periosteal apposition . INTRODUCTION To address the hypothesis that age-related changes in BMD and bone geometry may be different in men and women , we prospect ively examined volumetric BMD ( vBMD ) and structural bone parameters assessed by QCT among participants of the InCHIANTI study over a 6-yr follow-up . MATERIAL S AND METHODS Three hundred forty-five men and 464 women 21 - 102 yr of age from the InCHIANTI study , a population -based study in Tuscany , Italy , were included . Tibial QCT bone parameters were measured at enrollment ( 1998 - 2000 ) and at 3- ( 2001 - 2003 ) and 6-yr ( 2004 - 2006 ) follow-ups . RESULTS Periosteal apposition occurred both in men and women . The annual rate of bone periosteal apposition was higher in younger than in older men , whereas in women , the rate of apposition was homogenous across age groups . The age-related medullary expansion , expression of endocortical resorption , was significantly higher in women compared with men . In women , but not in men , accelerated endocortical resorption not sufficiently balanced by periosteal apposition caused accelerated loss in cortical bone mass . The cross-sectional moment of inertia decreased progressively over the life span in both sexes . CONCLUSIONS Endocortical resorption causes bone loss in older women despite periosteal apposition . Obtaining a balance between endocortical resorption and periosteal apposition should be the target for interventions aim ed to decrease bone loss and prevent osteoporosis in older women BACKGROUND Physical exercise affects many risk factors and diseases and therefore can play a vital role in general disease prevention and treatment of elderly individuals and may reduce costs . We sought to determine whether a single exercise program affects fracture risk ( bone mineral density [ BMD ] and falls ) , coronary heart disease ( CHD ) risk factors , and health care costs in community-dwelling elderly women . METHODS We conducted a r and omized , single-blinded , controlled trial from May 1 , 2005 , through July 31 , 2008 , recruiting women 65 years or older who were living independently in the area of Erlangen-Nuremberg , Germany . In all , 246 women were r and omly assigned to an 18-month exercise program ( exercise group ) or a wellness program ( control group ) . The exercise group ( n = 123 ) performed a multi purpose exercise program with special emphasis on exercise intensity ; the controls ( n = 123 ) focused on well-being with a low-intensity , low-frequency program . The main outcome measures were BMD , the number of falls , the Framingham-based 10-year CHD risk , and direct health care costs . RESULTS For the 227 women who completed the 18-month study , significant exercise effects were observed for BMD of the lumbar spine ( mean [ 95 % confidence interval ( CI ) ] percentage of change in BMD [ baseline to follow-up ] for the exercise group : 1.77 % [ 1.26 % to 2.28 % ] vs controls : 0.33 % [ -0.24 % to 0.91 % ] ; P < .001 ) , femoral neck ( exercise group : 1.01 % [ 0.37 % to 1.65 % ] vs controls : -1.05 % [ -1.70 % to -0.40 % ] ; P < .001 ) , and fall rate per person during 18 months ( exercise group : 1.00 [ 0.76 to 1.24 ] vs controls : 1.66 [ 1.33 to 1.99 ] ; P = .002 ) . The 10-year CHD risk was significantly affected in both subgroups ( absolute change for the exercise group : -1.96 % [ 95 % CI , -2.69 % to -1.23 % ] vs controls : -1.15 % [ -1.69 % to -0.62 % ] ; P = .22 ) , with no significant difference between the groups . The direct health care costs per participant during the 18-month intervention showed nonsignificant differences between the groups ( exercise group : 2255 euros[95 % CI , 1791 euros-2718 euros ] vs controls : 2780 euros [ 2187 euros-3372 euros ] ; P = .20 ) . CONCLUSION Compared with a general wellness program , our 18-month exercise program significantly improved BMD and fall risk , but not predicted CHD risk , in elderly women . This benefit occurred at no increase in direct costs . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00267839 This study was conducted to examine the effects of combined exercise on health-related fitness , endotoxin concentrations , and immune functions of postmenopausal women with abdominal obesity . 20 voluntary participants were recruited and they were r and omly allocated to the combined exercise group ( n = 10 ) or the control group ( n = 10 ) . Visceral obesity was defined as a visceral-to-subcutaneous fat ratio ≥0.4 based on computed tomography ( CT ) results . Body composition , exercise stress testing , fitness measurement , CT scan , and blood variables were analyzed to eluci date the effects of combined exercise . The SPSS Statistics 18.0 program was used to calculate means and st and ard deviations for all variables . Significant differences between the exercise group and control group were determined with 2-way ANOVA and paired t-tests . The exercise group 's abdominal obesity was mitigated due to visceral fat reduction ; grip strength , push-ups , and oxygen uptake per weight improved ; and HDL-C and IgA level also increased , while TNF-α , CD14 , and endotoxin levels decreased . Lowered TNF-α after exercise might have an important role in the obesity reduction . Therefore , we can conclude that combined exercise is effective in mitigating abdominal obesity , preventing metabolic diseases , and enhancing immune function Physical exercise is advised as a preventive and therapeutic strategy against aging-induced bone weakness . In this study we examined the effects of 8-month multicomponent training with weight-bearing exercises on different risk factors of falling , including muscle strength , balance , agility , and bone mineral density ( BMD ) in older women . Participants were r and omly assigned to either an exercise-training group ( ET , n = 30 ) or a control group ( CON , n = 30 ) . Twenty-seven subjects in the ET group and 22 in the CON group completed the study . Training was performed twice a week and was design ed to load bones with intermittent and multidirectional compressive forces and to improve physical function . Outcome measures included lumbar spine and proximal femoral BMD ( by dual X-ray absorptiometry ) , muscle strength , balance , h and grip strength , walking performance , fat mass , and anthropometric data . Potential confounding variables included dietary intake , accelerometer-based physical activity , and molecularly defined lactase nonpersistence . After 8 months , the ET group decreased percent fat mass and improved h and grip strength , postural sway , strength on knee flexion at 180 ° /s , and BMD at the femoral neck ( + 2.8 % ) . Both groups decreased waist circumference and improved dynamic balance , chair st and performance , strength on knee extension for the right leg at 180 ° /s , and knee flexion for both legs at 60 ° /s . No associations were found between lactase nonpersistence and BMD changes . Data suggest that 8 months of moderate-impact weight-bearing and multicomponent exercises reduces the potential risk factors for falls and related fractures in older women Abstract . Osteoporosis is one of the most common skeletal disorders affecting postmenopausal women . The purpose of this study was to investigate whether a 24-week program of aerobic high-impact loading exercise was beneficial for enhancing physical fitness and bone mineral density ( BMD ) in osteopenic postmenopausal women . Forty-three postmenopausal women aged 48–65 years participated in this study . The BMD of the spine ( L2–L4 ) and right femoral neck of each woman was below 1 SD of the mean of premenopausal women , as examined by dual X-ray absorptiometry . The assignment of subjects into exercise or control group was not r and omized but based on each subject 's anticipated compliance to the 6-month long exercise program . Twenty-two subjects joined the exercise group and attended the training programs and 21 served as the control group . Exercise programs included treadmill walking at an intensity above 70 % of maximal oxygen consumption ( VO2max ) for 30 minutes , followed by 10 minutes of stepping exercise using a 20-cm-high bench . The program was conducted three times per week for 24 weeks . Physical fitness measurements included testing of flexibility , muscular strength and endurance , body composition , and cardiopulmonary fitness . The results showed that the quadriceps strength , muscular endurance , and VO2max in the exercise group had significant improvements , whereas no improvement was found in any of the physical fitness parameters in the control group . The BMD of the L2–L4 and the femoral neck in the exercise group increased 2.0 % ( P > 0.05 ) and 6.8 % ( P < 0.05 ) and those in the control group decreased 2.3 % ( P < 0.05 ) and 1.5 % ( P > 0.05 ) , respectively . In conclusion , aerobics combined with high-impact exercise at a moderate intensity was effective in off setting the decline in BMD in osteopenic postmenopausal women Evidence of the effect of exercise on bone loss comes mainly from studies in voluntary postmenopausal women , and no population -based , long-term interventions have been performed . The purpose of this population -based , r and omized , controlled trial was to determine the effect of long-term impact exercise on bone mass at various skeletal sites in elderly women with low bone mineral density ( BMD ) at the radius and hip . Participants ( n = 160 ) were r and omly assigned to 30 months either of supervised and home-based impact exercise training or of no intervention . The primary outcome measures were femoral neck , trochanter and total hip BMD , and the secondary outcomes were bone density measures at the radius and calcaneum . Outcomes were assessed at baseline , 12 months and 30 months using blinded operators . The analyses were performed on an intention-to-treat analysis . Mean femoral neck and trochanter BMD decreased in the control group [ −1.1 % , 95 % confidence interval ( CI ) −0.1 % to −2.1 % and −1.6 % , 95 % CI −0.4 % to −2.7 % ] , while no change occurred in the exercise group . Mean trochanter BMC decreased more in the control group ( −7.7 % , 95 % CI −9.7 % to −5.6 % vs. −2.9 % , 95 % CI −5.3 to −0.9 ) . There were six falls that result ed in fractures in the exercise group and 16 in the control group during the 30-month intervention ( P = 0.019 ) . A significant bone loss occurred in both groups at the radius and calcaneum . In multivariate analysis , weight gain was associated with increased BMD and BMC at all femur sites both in the exercise group and in the pooled groups . In conclusion , impact exercise had no effect on BMD , while there was a positive effect on BMC at the trochanter . Exercise may prevent fall-related fractures in elderly women with low bone mass OBJECTIVE To describe the effect of a supervised physical activity program on the physical and psychological health of osteopenic women . DESIGN A r and omized controlled trial . SETTING Sherbrooke , Quebec , Canada . PARTICIPANTS A total of 124 community-living postmenopausal women , between 50 and 70 years of age , with low bone mass took part in the study . INTERVENTION Subjects allocated to the experimental group performed weight-bearing exercises ( walking , stepping up and down from benches ) , aerobic dancing , and flexibility exercises for 60 minutes , three times a week , over a period of 12 months . All subjects were invited to attend bi-monthly educational seminars covering topics related to osteoporosis . OUTCOME MEASURES Spinal and femoral bone mineral density ( BMD ) , functional fitness ( flexibility , coordination , agility , strength/endurance , cardiorespiratory endurance ) , psychological well-being , back pain intensity , and self-perceived health . RESULTS Spinal BMD stabilized in the exercisers while decreasing significantly in the controls ( P = .031 ) . No change in femoral BMD was observed in either group ( P = .597 ) . Four of the five parameters chosen to evaluate functional fitness , namely flexibility , agility , strength , and endurance , were affected positively by the exercise program ( all P < .01 ) . Adjusting for prescores by means of an analysis of covariance revealed a significant difference between the groups in psychological well-being , which favored the exercisers ( P = .012 ) . After 12 months , back pain reported by exercisers was lower than that reported by controls ( P = .008 ) . Finally , self-perceived health increased in the exercise group , whereas no difference was observed in the control group ( P = .790 ) . CONCLUSION These results suggest that after 12 months , exercising can produce a significant increase above initial levels in the functional fitness , well-being , and self-perceived health of osteopenic women . Intensity of back pain can also be lowered by exercise . The exercise program succeeded in stabilizing spinal BMD but had no effect on femoral BMD Osteoarthritis and osteoporosis often coexist in postmenopausal women . The simultaneous effect of bone-favorable high-impact training on these diseases is not well understood and is a topic of controversy . We evaluated the effects of high-impact exercise on bone mineral content ( BMC ) and the estimated biochemical composition of knee cartilage in postmenopausal women with mild knee osteoarthritis . Eighty women aged 50 to 66 years with mild knee osteoarthritis were r and omly assigned to undergo supervised progressive exercise three times a week for 12 months ( n = 40 ) or to a nonintervention control group ( n = 40 ) . BMC of the femoral neck , trochanter , and lumbar spine was measured by dual-energy X-ray absorptiometry ( DXA ) . The biochemical composition of cartilage was estimated using delayed gadolinium-enhanced magnetic resonance imaging ( MRI ) cartilage ( dGEMRIC ) , sensitive to cartilage glycosaminoglycan content , and transverse relaxation time ( T2 ) mapping that is sensitive to the properties of the collagen network . In addition , we evaluated clinical ly important symptoms and physical performance-related risk factors of falling : cardiorespiratory fitness , dynamic balance , maximal isometric knee extension and flexion forces , and leg power . Thirty-six trainees and 40 controls completed the study . The mean gain in femoral neck BMC in the exercise group was 0.6 % ( 95 % CI , -0.2 % to 1.4 % ) and the mean loss in the control group was -1.2 % ( 95 % CI , -2.1 % to -0.4 % ) . The change in baseline , body mass , and adjusted body mass change in BMC between the groups was significant ( p = 0.005 ) , whereas no changes occurred in the biochemical composition of the cartilage , as investigated by MRI . Balance , muscle force , and cardiorespiratory fitness improved significantly more ( 3 % to 11 % ) in the exercise group than in the control group . Progressively implemented high-impact training , which increased bone mass , did not affect the biochemical composition of cartilage and may be feasible in the prevention of osteoporosis and physical performance-related risk factors of falling in postmenopausal women Objective : The study was design ed to evaluate the effects of strength training ( ST ) on the bone mineral density ( BMD ) of postmenopausal women without hormone replacement therapy . Method : Subjects were r and omized into untrained ( UN ) or trained ( TR ) groups . The TR group exercised three ST sessions per week for 24 weeks , and body composition , muscular strength , and BMD of the lumbar spine and femur neck were evaluated . Results : Body weight , mass index , and fat percentage were lower after 24 weeks only in the TR group ( p < .05 ) . SR also improved the one repetition maximum test in 46 % and 39 % of upper and lower limbs , respectively . The percentage of demineralization was higher in the UN group than in the TR group at the lumbar spine and femoral neck ( p < .05 ) . Discussion : Results indicated that 24 weeks of ST improved body composition parameters , increased muscular strength , and preserved BMD in postmenopausal women Objectives —There is a paucity of long term studies on exercise training in elderly women . The purpose of this study was to investigate the effects of one year of progressive resistance exercise ( PRE ) on dynamic muscular strength and the relations to bone mineral density ( BMD ) in elderly women . Methods —Forty four healthy sedentary women ( mean age 68.8 years ) volunteered for this study and were r and omly assigned to either an exercise group or a control group . The exercise group were involved in three one hour sessions a week for 52 weeks of supervised PRE to strengthen the large muscle groups of the body , while the control group were instructed to continue their normal lifestyle . The exercise circuit included three sets of eight repetitions at 75 % of one repetition maximum focused on the large muscle groups . BMD was measured by dual energy x ray absoptiometry ( Lunar DPX ) at the lumbar spine and at three sites in the proximal femur . Other selected parameters of physical fitness were also measured . Results —Statistical analyses ( analysis of covariance ) showed significant strength gains ( p<0.01 ) in bilateral bench press ( > 29 % ) , bilateral leg press ( > 19 % ) , and unilateral biceps curl ( > 20 % ) . No significant difference between groups was evident in body weight , grip strength , flexibility , waist to hip ratio , or the sum of eight skinfolds . Significant relations ( p<0.05 ) were recorded between dynamic leg strength and the BMD of the femoral neck , Ward 's triangle , and the lumbar spine . Conclusions —Significant strength changes , after one year of PRE , were evident in elderly women , and the muscle increases may parallel changes in BMD ; however , correlation coefficients were moderate |
12,969 | 28,573,755 | In this review , nearly all dentifrices that are specifically formulated for tooth whitening were shown to have a beneficial effect in reducing ETD , irrespective of whether or not a chemical discoloration agent was added | OBJECTIVE The aim of this systematic review was to assess the effect of a whitening dentifrice ( WDF ) relative to a regular dentifrice ( RDF ) on the reduction of natural extrinsic tooth surface discoloration ( ETD ) . | The objective of this double-blind clinical study was to compare the tooth whitening efficacy ( stain removal ) of a new commercially available tooth whitening dentifrice ( Colgate Total Plus Whitening Toothpaste ) containing 0.2 % triclosan and 3.0 % PVM/MA copolymer in a 0.243 % sodium fluoride/high cleaning silica base , with that of two commercially available dentifrices , Crest Multi-Care Advanced Cleaning Toothpaste and Colgate Winterfresh Gel Fluoride Toothpaste . Following a baseline examination to assess extrinsic tooth stain , qualifying adult male and female subjects were r and omized into three treatment groups which were balanced for gender , age and level of extrinsic tooth stain . Subjects were asked to brush their teeth twice ( morning and evening ) for one minute with their assigned dentifrice using a soft-bristled toothbrush . Examinations for extrinsic tooth stain were repeated after six weeks ' use of the study dentifrices . One-hundred and twenty-three ( 123 ) subjects complied with the protocol and completed the study . At the six-week examination , subjects assigned to the Colgate Total Plus Whitening Toothpaste treatment group exhibited statistically significant reductions in extrinsic tooth stain area and extrinsic tooth stain intensity relative to those subjects assigned to the Crest Multi-Care Advanced Cleaning Toothpaste and the Colgate Winterfresh Gel Fluoride Toothpaste The objective of this double-blind clinical study was to investigate the tooth whitening efficacy of a new commercially available calculus-inhibiting dentifrice ( Colgate Tartar Control Plus Whitening Fluoride dentifrice ) containing tetra-sodium pyrophosphate , sodium tripolyphosphate , and PVM/MA copolymer in a 0.243 % sodium fluoride/silica base ( test dentifrice ) , compared to a commercially available , non-tooth whitening dentifrice containing 0.243 % sodium fluoride in a silica base ( control dentifrice ) . Following a baseline examination for , extrinsic tooth stain , qualifying adult male and female subjects from the Manchester , United Kingdom area were r and omized into two treatment groups which were balanced for gender , age and level of extrinsic tooth stain . Subjects were instructed to brush their teeth twice daily ( morning and evening ) for one minute with their assigned dentifrice using a soft-bristled toothbrush . Examinations for extrinsic tooth stain were repeated after six weeks ' use of the study dentifrices . Seventy-nine(79 ) subjects complied with the protocol and completed the entire study . At the six-week examination , subjects assigned to the test dentifrice treatment group exhibited statistically significant reductions of over 40 % with respect to both extrinsic tooth stain area and extrinsic tooth stain intensity relative to those subjects assigned to the control dentifrice treatment group The objective of this double-blind clinical study was to compare the efficacy for extrinsic tooth stain removal of four commercially available dentifrices : Colgate Tartar Control with Baking Soda & Peroxide Fluoride Toothpaste ; Aquafresh Advanced Whitening Toothpaste with Fluoride ; Rembr and t Tartar Control Low Abrasion Fluoride Whitening Toothpaste ; and Crest Regular Fluoride Toothpaste . Following a baseline examination for extrinsic tooth stain on the anterior six m and ibular and maxillary teeth , qualifying adult male and female subjects from the Philadelphia , Pennsylvania area were r and omized into four treatment groups which were balanced for age , gender , tobacco habits , and level of extrinsic tooth stain . Subjects were instructed to brush their teeth twice daily ( morning and evening ) for one minute with their assigned dentifrice using a soft-bristled toothbrush . Examinations for extrinsic tooth stain were repeated after six weeks ' use of the study dentifrices . One hundred eighty ( 180 ) subjects complied with the protocol , and completed the entire study . At the six-week examination , subjects assigned to the Colgate Tartar Control with Baking Soda & Peroxide Fluoride Toothpaste treatment group exhibited statistically lower levels of extrinsic tooth stain area and extrinsic tooth stain intensity than did those subjects assigned to the Crest Regular Fluoride treatment group . Subjects assigned to the Aquafresh Advanced Whitening treatment group exhibited significantly lower levels of extrinsic tooth stain area than did those assigned the Crest Regular Fluoride group . No other significant differences among the four study dentifrices were noted . Thus , the results of this double-blind clinical study support the conclusion that Colgate Tartar Control with Baking Soda & Peroxide Fluoride Toothpaste provides significantly greater control of extrinsic tooth stain than does Crest Regular Fluoride , a sodium fluoride/silica dentifrice OBJECTIVE The objective of this clinical investigation was to evaluate the effectiveness in removing existing extrinsic tooth stains of a sodium bicarbonate ( baking soda ) , dual-phase dentifrice containing calcium and phosphate ( Test Dentifrice ) , when compared to a commercial hydrated silica dentifrice ( Control Dentifrice ) , during a six-week period of normal , unsupervised use . METHODOLOGY This investigation was a double-blind comparison of two equivalent , parallel groups of subjects assigned to use different dentifrices for six weeks . A total of 108 adult male and female subjects qualified for the trial based on the presence of existing extrinsic tooth stains and other inclusion /exclusion criteria . The two groups were balanced for gender , tobacco use , and extrinsic tooth stain scores , and r and omly assigned the Test or Control dentifrices . All subjects were instructed to brush their teeth twice daily using only the dentifrice and toothbrush provided , and to refrain from using any other oral hygiene products for the duration of the study . Although product usage was unsupervised after the baseline visit , subjects maintained a treatment diary , and product consumption was monitored to estimate compliance . Oral soft and hard tissue and extrinsic stain assessment s ( Modified Lobene Stain Index ) for each subject were conducted at baseline and after two , four , and six weeks of product use . RESULTS A total of 107 subjects complied with the protocol and completed the six-week study . Compared to baseline , at the two- , four- , and six-week examinations the Test Dentifrice group had statistically significant reductions in extrinsic tooth stain . In contrast , the Control Dentifrice group did not attain significant reductions from baseline at any of the exams . At both the four-week and six-week examinations , the Test Dentifrice group had significantly lower levels of extrinsic tooth stain than the Control Dentifrice group . CONCLUSION A sodium bicarbonate , dual-phase dentifrice containing calcium and phosphate demonstrated statisically significant efficacy in removing naturally acquired , extrinsic tooth stain , and was significantly more effective for stain removal than a commercially available , hydrated silica dentifrice The effect of twice-daily brushing with one of three different dentifrices ( Arm & Hammer Dental Care , Arm & Hammer Dental Care Extra Whitening , Crest ) on stain removal and tooth whitening was examined in 115 volunteers over a period of 12 weeks . The facial surfaces of 12 anterior teeth were assessed for stain using a published , modified version of a st and ard stain index . Whiteness was measured on teeth 8 and 9 using a single Vita Lumin-Vaccum Shade Guide for consistency . At baseline , the mean facial stain scores were significantly higher ( p < 0.05 - 0.01 ) for both Arm & Hammer dentifrices than for Crest . In addition , the tooth shades , as indicated by the stain guide , specifically the b * values representing yellowness , were quantified using a Minolta spectrophotometer . Arm & Hammer Dental Care Extra Whitening formula was found to be significantly better than Crest at removing naturally occurring extrinsic stain . The difference between Arm & Hammer Dental Care Extra Whitening and Crest became significant ( p < 0.01 ) after two weeks of use , and remained intact during the balance of the study , achieving p values of 0.0002 for at least one of the three assessed parameters ( total stain , proximal , and facial ) at weeks 4 and 12 . The study also found that Arm & Hammer Dental Care produced a significant increase in tooth whiteness by week 12 , whereas Crest showed no such increase at any time during the study . These results suggest that the two Arm & Hammer Baking Soda products are more effective in reducing stain and increasing whiteness than the st and ard silica-based dentifrice . Their effectiveness is not related to abrasivity since they are less abrasive to tooth enamel than the silica-based product tested OBJECTIVES To evaluate a modified tooth stain index and determine the effect of dietary factors on stain formation . METHODS At baseline , 182 adult volunteers were given a full oral prophylaxis followed by stain assessment using a modification of the Lobene index . This involved assigning separate scores to the mesial ( M ) and distal ( D ) sites of each tooth , in addition to the st and ard gingival area ( G ) and tooth body ( B ) . For each site , stain intensity and areas were scored . The sum of ( intensity X area ) scores was calculated for all sites ( GBMD-value ) and for the gingival and body sites only ( GB-value ) . The subjects used a st and ard abrasive dentifrice and a soft toothbrush for 6 weeks . RESULTS Stain was reassessed and the average increase in GBMD-value was 20.9 ( sd=9.9 ) ( buccal aspect ) and 29.9 ( sd=18.0 ) ( lingual aspect ) . The corresponding GB-values were 4.4 ( sd=4.8 ) and 12.5 ( sd=10.2 ) . The coefficients of variation of the GBMD index values were consistently lower than those of the GB values . Smoking and tea-drinking were found to be the only significant ( p<0.001 ) factors investigated for stain formation . CONCLUSIONS It is concluded that the modified index may well be advantageous to its conventional counterpart because sites with most visible stain are assessed separately and because it may also offer higher discriminatory power due to a lower coefficient of variation OBJECTIVE The primary purpose of this r and omized , controlled , six-week clinical trial was to determine the effectiveness and safety of a new whitening dentifrice in removing extrinsic tooth stain and whitening teeth . An additional two-week exploratory study was conducted to determine whether the whitening or stain-prevention activity of the dentifrice would persist following cessation of use . METHODS In the first study ( Phase I ) , one-hundred and forty-six qualifying subjects were r and omly assigned to either a sodium bicarbonate whitening dentifrice group ( Arm & Hammer Advance White Extreme Whitening Baking Soda and Peroxide Toothpaste ) or a silica-based negative control dentifrice group , and brushed twice daily with their assigned dentifrice for six weeks . Tooth shade on the labial surfaces of the eight incisors was assessed using a Vita Classic shade guide , and extrinsic tooth stain was scored using a Modified Lobene Stain Index ( MLSI ) at baseline , week 4 , and week 6 . In Phase II ( after the week 6 examination ) , volunteers from the Arm & Hammer whitening dentifrice group were r and omly assigned to continue using the whitening dentifrice or to use the negative control dentifrice twice daily for two weeks . The six-week shade and stain index scores served as the baseline for this exploratory phase and were rescored after two weeks . RESULTS The whitening dentifrice group had statistically significant ( p < 0.0001 ) mean shade score reductions of 1.82 and 2.57 from baseline to weeks 4 and 6 , respectively . For the same periods , the negative control dentifrice group was virtually unchanged from baseline . For tooth stain , the MLSI total mean scores for the whitening dentifrice group showed statistically significant ( p < 0.0001 ) decreases from baseline of 1.42 ( 41.6 % ) and 2.11 ( 61.6 % ) at weeks 4 and 6 , respectively . In contrast , the negative control dentifrice group had a MLSI reduction of 0.07 at week 4 and a 0.06 increase at week 6 . Between-group analyses using baseline-adjusted ANCOVA showed the whitening dentifrice to be statistically significantly more effective ( p < 0.0001 ) than the negative control for shade and tooth stain reductions for all index comparisons . Compared to the six-week ( baseline ) scores , subjects who continued to use the whitening dentifrice for the additional two weeks experienced statistically significant ( p < 0.0001 ) further mean reductions of 0.88 in shade score and 0.46 in MLSI score , while subjects who switched to the negative control dentifrice experienced smaller , statistically significant ( p < 0.05 ) reductions of 0.34 in shade score and 0.13 in total MLSI score . CONCLUSION The Arm & Hammer whitening dentifrice tested in this study is effective for removing extrinsic tooth stain and whitening teeth . While the results also suggest that this dentifrice may have stain-prevention activity that persists following cessation of product use , such activity would need to be confirmed with further studies The objective of this double-blind clinical study was to investigate the tooth whitening efficacy of a new dentifrice ( Colgate Tartar Control Plus Whitening Fluoride Toothpaste ) for the removal of extrinsic tooth stain , through a comparison with two commercially available dentifrices , Aquafresh Whitening Toothpaste with Fluoride , and Crest Regular Fluoride Toothpaste . Following a baseline examination for extrinsic tooth stain area and intensity , qualifying adult male and female subjects from the Mississauga , Ontario , Canada area were r and omized into three treatment groups which were balanced for age , gender , and level of extrinsic tooth stain . Subjects were instructed to brush their teeth twice daily ( morning and evening ) for one minute with their assigned dentifrice using a soft-bristled toothbrush . Examinations for extrinsic tooth stain were repeated after six weeks ' use of the study dentifrices . One hundred twenty-two ( 122 ) subjects complied with the protocol and completed the entire study . At the six-week examination , subjects assigned to the Colgate Tartar Control Plus Whitening treatment group and subjects assigned to the Aquafresh Whitening treatment group exhibited statistically lower levels ( p < 0.0001 ) of extrinsic tooth stain area and intensity than did those subjects assigned to the Crest Regular Fluoride treatment group . Further , subjects assigned to the Colgate Tartar Control Plus Whitening treatment group exhibited significantly lower levels of extrinsic tooth stain area and intensity than did those assigned to the Aquafresh Whitening treatment group ( p < 0.0001 ) The objective of this double-blind clinical study was to investigate the tooth whitening efficacy of a variation in formula of a commercially available dentifrice ( Colgate Total Toothpaste ) . The variation ( Colgate Total Plus Whitening Toothpaste ) was the addition of high cleaning silica to the existing formulation . Following a baseline examination for extrinsic tooth stain , qualifying adult male and female subjects from the Mississauga , Ontario , Canada area were r and omized into two treatment groups which were balanced for gender , age and level of extrinsic tooth stain . Subjects were instructed to brush their teeth twice daily ( morning and evening ) for one minute with their assigned dentifrice , using a soft-bristled toothbrush . Examinations for extrinsic tooth stain were repeated after six weeks ' use of the study dentifrices . Ninety-three ( 93 ) subjects complied with the protocol and completed the entire study . At the six-week examination , subjects assigned to the new dentifrice formulation group exhibited statistically significantly lower levels of extrinsic tooth stain area and extrinsic tooth stain intensity than did those subjects assigned to the Colgate Total Toothpaste group AIM To assess extrinsic stain removal efficacy of a power toothbrush and a dental prophylaxis followed by the use of a st and ardized American Dental Association ( ADA ) reference manual toothbrush . METHODS AND MATERIAL S This was a r and omized , positive-controlled , examiner-blind , parallel group , two-week study . A Lobene stain examination was performed at baseline . Subjects were r and omized to one of two treatment groups : Group 1 : Oral-B Vitality Pro White power toothbrush or Group 2 : Subjects receiving a dental prophylaxis then using a st and ardized ADA reference manual toothbrush . Subjects were instructed to brush their teeth with the assigned toothbrush and a fluoride dentifrice in front of a mirror twice per day for 2 minutes . Stain was reassessed following 2 weeks of brushing . RESULTS A significant reduction ( p < 0.001 ) in mean Lobene composite scores after 2 weeks was found for Group 1 ( 90.6 % ) and Group 2 ( 94.4 % ) . Both groups also showed a significant reduction ( p < 0.001 ) in extent and intensity scores . There was no significant group difference in reduction in mean Lobene composite scores ( p>0.1 ) . CONCLUSIONS The Oral-B Vitality Pro White power toothbrush showed effective stain removal at a level similar to receiving an oral prophylaxis followed by the use of an ADA reference manual toothbrush . CLINICAL SIGNIFICANCE In this small study the Oral-B Vitality Pro White power toothbrush achieved statistically significant stain removal between dental visits OBJECTIVES This clinical trial tested the anti-stain efficacy at 3 and 6 months of a novel , sodium polyaspartate-containing , anti-stain dentifrice . In addition , the efficacy of the new dentifrice in controlling gingival inflammation and inhibition of calculus deposition was tested . METHODS Participants were recruited to this double blind r and omised control clinical trial , and allocated to either test or control groups . The presence of stain and calculus were entry criteria . Measurements of stain , calculus and gingival inflammation were recorded using the Shaw and Murray Stain score , Volpe-Manhold Calculus score and the Modified Gingival Index respectively . Measurements were made at baseline , prior to the removal of stain and calculus , and after 3 and 6 months . Missing data were imputed by and the outcomes were analysed using univariate analysis . RESULTS At three months , toothpaste containing sodium polyaspartate was better ( difference of mean 1.13 with SEM 0.57 ) than control for the control of dental stain ( p<0.05 ) . Stain scores also showed a trend in favour of the test product ( difference of mean 1.03 with SEM 0.78 ) at six months ( p>0.05 ) . There was no difference between toothpastes with respect to calculus deposition or gingival inflammation . CONCLUSIONS Toothpaste containing sodium polyaspartate was more effective than a control toothpaste at preventing deposition of dental stain for 3 months after professional tooth cleaning but showed no significant effect at 6 months . CLINICAL RELEVANCE Sodium polyaspartate toothpaste was more effective than a control toothpaste at preventing dental stain formation and maybe helpful in controlling staining between episodes of scaling and polishing The objective of this double-blind clinical study was to compare the extrinsic tooth stain removal efficacy of three commercially available dentifrices : Colgate Platinum Whitening Toothpaste with Fluoride , Aquafresh Advanced Whitening Toothpaste with Fluoride , and Crest Regular Fluoride Toothpaste . Following a baseline examination for extrinsic tooth stain , qualifying adult male and female subjects from the Toronto , Ontario , Canada are were r and omized into three treatment groups which were balanced for age , gender , tobacco habits , and level of extrinsic tooth stain using the Lobene Stain Index . Subjects were instructed to brush their teeth twice daily ( morning and evening ) for one minute with their assigned dentifrice using a soft-bristled toothbrush . Examinations for extrinsic tooth stain were repeated after six weeks ' use of the study dentifrices . One-hundred forty-nine ( 149 ) subjects complied with the protocol and completed the entire study . At the six-week examination , subjects assigned to the Colgate Platinum treatment group exhibited statistically significant reductions ( p < 0.05 ) from baseline level with respect to extrinsic tooth stain area ( 49.4 % reduction ) and extrinsic tooth stain intensity ( 52.4 % reduction ) . Statistically significant reductions ( p < 0.05 ) for both extrinsic tooth stain parameters were also exhibited by the subjects assigned to the Aquafresh Whitening treatment group ( 14.0 % reduction for area , 15.5 % reduction for intensity ) . Both tooth whitening treatments provided statistically significantly greater reductions ( p < 0.05 ) in extrinsic tooth stain than did the Crest Regular Fluoride dentifrice , which exhibited a small increase in the extrinsic tooth stain parameters over the course of the study . Additionally , the Colgate Platinum dentifrice provided statistically significantly ( p < 0.05 ) greater removal of extrinsic tooth stain over the course of this six-week study than did the Aquafresh Whitening dentifrice . Thus , the results of the double-blind clinical study support the conclusion that the two tooth whitening dentifrices , Colgate Platinum and Aquafresh Whitening , provide significantly greater ( p < 0.05 ) removal of extrinsic tooth stain than does Crest Regular Fluoride , a sodium fluoride/silica dentifrice . Further , the results of the study support the conclusion that Colgate Platinum dentifrice provides a greater ( p < 0.05 ) level of extrinsic tooth stain removal efficacy than does Aquafresh Whitening dentifrice The objective of this double-blind clinical study was to investigate the tooth whitening efficacy of a formulation variant of a commercially available dentifrice ( Colgate Total Plus Whitening Toothpaste ) obtained by the addition of high-cleaning silica , relative to that of its currently marketed formulation ( Colgate Total Toothpaste ) . Following a baseline examination for extrinsic tooth stain , qualifying adult male and female subjects from New Jersey and Florida were r and omized into two treatment groups which were balanced for gender , age , and level of extrinsic tooth stain . Subjects were instructed to brush their teeth twice daily ( morning and evening ) for one minute with their assigned dentifrice using a soft-bristled toothbrush . Examinations for extrinsic tooth stain were repeated after six-weeks ' , three-months ' and six-months ' use of the study dentifrices . Eighty-six ( 86 ) subjects complied with the protocol and completed the entire study . At the six-month examination , subjects assigned to the new dentifrice formulation group exhibited statistically significantly lower levels of extrinsic tooth stain area and extrinsic tooth stain intensity than did those subjects assigned to the Colgate Total Toothpaste group . Thus , the results of this double-blind clinical study support the conclusion that the new dentifrice formulation variant is efficacious , compared to the control dentifrice , for the removal of extrinsic tooth stain OBJECTIVE To examine the effects of routine use of two dentifrices on tooth stain . BASIC RESEARCH DESIGN Single centre , parallel design , double blind r and omised clinical study with two treatment groups . CLINICAL SETTING Department of Dental Public Health , SDM College of Dental Sciences and Hospital , Dharwad , Karnataka , India . PARTICIPANTS 125 of the 140 study subjects aged 18 - 70 years completed the 8-week study period . INTERVENTIONS Subjects were r and omly assigned to brush twice daily with fluoride toothpaste ( control ) or a dentifrice formulated with silicas ( test ) and recalled for tooth stain examinations after 4 and 8 weeks of dentifrice use . MAIN OUTCOME MEASURES Modified Lobene tooth stain index . RESULTS Whereas statistical analyses indicate no significant differences between the treatment groups for baseline scores of tooth stain intensity , stain area and tooth stain composite scores ( p > 0.53 ) , examinations demonstrate significant reductions in stain area , intensity and stain composite scores amongst subjects assigned the test dentifrice at both recall visits versus the control ( p < 0.05 ) . CONCLUSIONS Routine use of the test dentifrice demonstrated significant removal of tooth stain among individuals recruited from the community OBJECTIVE The objective of these two six-week , double-blind clinical studies was to compare the extrinsic stain prevention ( Study # 1 ) and stain removal ( Study # 2 ) efficacy of a new dentifrice ( Colgate Total Advanced Toothpaste ) containing 0.3 % triclosan/ 2.0 % polyvinylmethyl ether/maleic acid ( PVM/MA ) copolymer/0.243 % sodium fluoride in a 17 % dual silica base , to a commercially available fluoride dentifrice without tooth whitening ingredients ( Crest Cavity Protection Toothpaste ) containing 0.243 % sodium fluoride in a silica base . METHODS Following baseline examinations for extrinsic tooth stain and an oral tissue examination , qualifying adult male and female subjects from the northern and central New Jersey , USA areas were r and omized for each study into two treatment groups which were balanced for gender and level of extrinsic tooth stain . Subjects received a full oral prophylaxis at the start of Study # 1 only . All subjects were provided with their assigned product and a soft-bristled adult toothbrush for home use . Subjects were instructed to brush their teeth for one minute twice daily ( morning and evening ) using only the dentifrice and toothbrush provided , and to refrain from using any other oral hygiene products for the entire six weeks of the study . There were no restrictions regarding diet or smoking habits during the course of the study . Examinations for extrinsic tooth stain and oral tissue assessment s were repeated after three weeks and six weeks of product use . RESULTS One-hundred fourteen ( 114 ) subjects participating in Study # 1 and 119 subjects participating in Study # 2 complied with the protocol and completed the entire study . In both studies , at the three-week and the six-week examinations , subjects who used the new dentifrice exhibited statistically significantly lower levels of extrinsic tooth stain area and extrinsic tooth stain intensity than did those subjects who used the commercially available fluoride control dentifrice . CONCLUSION A new dentifrice containing 0.3 % triclosan/2.0 % PVM/MA copolymer/0.243 % sodium fluoride in a 17 % dual silica base is more efficacious in the prevention and removal of extrinsic tooth stain than a commercially marketed fluoride dentifrice PURPOSE To evaluate the extrinsic stain removal benefit of a sodium hexametaphosphate containing dual-phase dentifrice ( Crest Vivid White ) relative to a marketed negative control ( Colgate Cavity Protection ) . METHODS This was a parallel groups , examiner-blind , r and omized and controlled clinical trial . A total of 200 healthy adults with natural stain on their anterior teeth were enrolled into the study . Following baseline examination , subjects were r and omly assigned to one of the two treatment groups based on baseline Lobene composite scores , smoking status ( yes/no ) , tea/coffee consumption ( yes/no ) , and gender . Subjects brushed twice daily , at least 1 minute every time over 6 weeks . Clinical examinations including extrinsic stain evaluation and oral soft tissue examination were conducted at BL , Weeks 3 and 6 . Extrinsic stain removal was evaluated on the anterior teeth by a dental examiner using Lobene stain index . RESULTS Of the 200 subjects who were r and omized to treatment , 195 were available for the 3-week examination and 193 subjects completed the study . The dual-phase dentifrice exhibited a statistically significant ( P < 0.01 ) reduction in Lobene stain composite scores when compared to the negative control dentifrice at Week 6 . Adjusted mean Lobene composite reduction for the dual-phase dentifrice group ( 0.32 ) was twice as big as the negative control group ( 0.16 ) . Change in Lobene stain extent ( area ) contributed primarily to the overall composite score reduction . All test products were well tolerated over the 6-week treatment period PURPOSE To evaluate the 6-week effect on natural extrinsic dental stain from the use of a dentifrice containing 10 % aluminum oxide , 1500 ppm sodium monofluorophosphate in a precipitated calcium carbonate ( PCC ) base or a second dentifrice containing 0.5 % calcium peroxide ( CP ) , 1500 ppm sodium monofluorophosphate in a PCC base compared to a fluoride placebo dentifrice without stain removal ingredients . MATERIAL S AND METHODS A total of 94 subjects were entered in the study , and stratified into three balanced groups according to their baseline mean Lobene Stain Index scores . The three groups were r and omly assigned to use one of the two test dentifrices or the placebo dentifrice . The three groups were well balanced with regard to their mean baseline stain index scores , gender and tobacco habits . Subjects were instructed to brush their teeth twice daily ( morning and evening ) for 1 minute with their assigned dentifrice and a commercially available soft bristled toothbrush . Extrinsic dental stain examinations , which included mean stain area and mean stain intensity , were conducted at baseline and 6 weeks . Examinations were conducted by the same dental examiner ( F.A. ) on the subjects at each examination . RESULTS After 6 weeks ' use of their assigned products , those subjects in the aluminum oxide/PCC dentifrice group and those subjects in the CP/PCC dentifrice group demonstrated statistically significant improvements , as compared to the fluoride placebo dentifrice group without stain removal ingredients BACKGROUND The biofilm that forms and remains on tooth surfaces is the main etiological factor in caries and periodontal disease . Prevention of caries and periodontal disease must be based on means that counteract this bacterial plaque . OBJECTIVE To monitor the incidence of tooth loss , caries and attachment loss during a 30-year period in a group of adults who maintained a carefully managed plaque control program . In addition , a comparison was made regarding the oral health status of individuals who , in 1972 and 2002 , were 51 - 65 years old . MATERIAL AND METHODS In 1971 and 1972 , more than 550 subjects were recruited . Three hundred and seventy-five subjects formed a test group and 180 a control group . After 6 years of monitoring , the control group was discontinued but the participants in the test group was maintained in the preventive program and was finally re-examined after 30 years . The following variables were studied at Baseline and after 3 , 6 , 15 and 30 years : plaque , caries , probing pocket depth , probing attachment level and CPITN . Each patient was given a detailed case presentation and education in self-diagnosis . Once every 2 months during the first 2 years , once every 3 - 12 months during years 3 - 30 , the participants received , on an individual need basis , additional education in self-diagnosis and self-care focused on proper plaque control measures , including the use of toothbrushes and interdental cleaning devices ( brush , dental tape , toothpick ) . The prophylactic sessions that were h and led by a dental hygienist also included ( i ) plaque disclosure and ( ii ) professional mechanical tooth cleaning including the use of a fluoride-containing dentifrice/paste . RESULTS Few teeth were lost during the 30 years of maintenance ; 0.4 - 1.8 in different age cohorts . The main reason for tooth loss was root fracture ; only 21 teeth were lost because of progressive periodontitis or caries . The mean number of new caries lesions was 1.2 , 1.7 and 2.1 in the three groups . About 80 % of the lesions were classified as recurrent caries . Most sites , buccal sites being the exception , exhibited no sign of attachment loss . Further , on approximal surfaces there was some gain of attachment between 1972 and 2002 in all age groups . CONCLUSION The present study reported on the 30-year outcome of preventive dental treatment in a group of carefully monitored subjects who on a regular basis were encouraged , but also enjoyed and recognized the benefit of , maintaining a high st and ard of oral hygiene . The incidence of caries and periodontal disease as well as tooth mortality in this subject sample was very small . Since all preventive and treatment efforts during the 30 years were delivered in one private dental office , caution must be exercised when comparisons are made with longitudinal studies that present oral disease data from r and omly selected subject sample In the GRADE approach , r and omized trials are classified as high quality evidence and observational studies as low quality evidence but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted A staining index has been proposed which is simple to use clinical ly and yet is sensitive enough to detect small changes in staining levels between different groups . Accurate scale drawings from An atlas of tooth form were reproduced . Outlines of the labial and lingual surfaces of all eight incisor teeth were enlarged to scale ( magnification X 4 ) and each tooth face divided into 4-mm squares . All areas of extrinsic stain were drawn by the examiner on the grid system . This method has been tested in three clinical trials and the reproducibility investigated . In 161 duplicate examinations a total of 1,830 stained squares were scored by one examiner , compared with 1,853 squares by the second examiner ; the reproducibility ratio was 0.155 and the coefficient of correlation was 0.956 . The method proved sufficiently sensitive to record differences in staining levels in groups using two dentifrices ; one was a normal commercial product with an abrasivity against dentin approximately two-thirds that of the other paste . The proposed Extrinsic Stain Index provides data which can be analyzed by appling parametric or nonparametric tests PURPOSE To evaluate the extrinsic stain removal efficacy of a new Pro-Argin formula whitening dentifrice containing 8.0 % arginine , a high cleaning calcium carbonate and 1450 ppm fluoride , as monofluorophosphate , after brushing twice daily for 4 and 8 weeks . METHODS At the baseline visit , 92 adult subjects were stratified based on their Lobene Stain Index scores and r and omized into two treatment groups ; one using the new Pro-Argin formula whitening dentifrice ( test group ) and the other using the original Pro-Argin formula dentifrice ( control group ) . Subjects were instructed to brush twice daily for the duration of the study . Tooth stain evaluations were conducted as stain area and stain intensity according to the Lobene Stain Index . RESULTS All 92 enrolled subjects complied with the protocol and completed the 8-week study . Baseline scores demonstrated no significant differences between the two treatment groups for the evaluated area and intensity parameters of stain ( P > 0.05 ) . At both the 4- and 8-week post-use evaluations , subjects brushing with the test dentifrice demonstrated significant reductions for all stain parameters versus the control ( P < 0.05 ) . Relative to the control group , the test group demonstrated reductions in mean stain intensity scores of 9.7 % and 17.9 % at the 4- and 8-week evaluations , respectively . Corresponding reductions in mean stain area scores for the test group relative to the control were 11.7 % and 20.8 % at the 4- and 8-week evaluations , respectively . ( Am JDent 2010;23 Sp Is A:36A-40A ) The objective of this double-blind clinical study was to investigate the tooth whitening efficacy of a formulation variant of a commercially available dentifrice ( Colgate Total Plus Whitening Toothpaste ) obtained by the addition of high cleaning silica , relative to that of its currently marketed formulation ( Colgate Total Toothpaste ) . Following a baseline examination , qualifying adult male and female subjects were r and omized into two treatment groups which were balanced for age , gender and level of extrinsic tooth stain . Subjects were instructed to brush their teeth twice daily ( morning and evening ) for one minute with their assigned dentifrice , using a soft-bristled toothbrush . After one , and again after two weeks ' use of the assigned dentifrices , a r and omly selected panel of subjects was examined for soft tissue findings . Examinations for extrinsic tooth stain were repeated for all subjects after six weeks ' use of the study dentifrices . Ninety-seven ( 97 ) subjects complied with the protocol and completed the entire study . At the six-week examination , subjects assigned to the new dentifrice formulation group exhibited statistically significantly ( p < 0.05 ) lower levels of extrinsic tooth stain area and extrinsic tooth stain intensity than did those subjects assigned to the Colgate Total Toothpaste group . Thus , the results of this double-blind clinical study support the conclusion that the new dentifrice formulation variant is efficacious for the removal of extrinsic tooth stain This six-week double-blind clinical study compared the toothwhitening effects of a new calculus-inhibiting dentifrice containing pyrophosphate , tripolyphosphate and copolymer in a 0.243 sodium fluoride/silica base ( Test Dentifrice ) with two commercially available dentifrices : Aquafresh Whitening Toothpaste with Fluoride and Crest Regular Fluoride Toothpaste . After a baseline examination for extrinsic tooth stain , qualifying adult males and females from Manchester , United Kingdom and from Mississauga , Ontario , Canada were r and omly assigned into three test groups . Each group was balanced for gender , tobacco habits and levels of tooth stain . Subjects were to brush their teeth twice daily with a soft-bristled toothbrush using the assigned toothpaste . One-hundred and twenty-eight ( 128 ) subjects complied with instructions and completed the trial . Subjects using the Test Dentifrice exhibited statistically less stain area and less stain intensity than did either the Aquafresh or Crest groups . Crest Regular Fluoride toothpaste was statistically less effective than Aquafresh Whitening toothpaste in removing stain . Results in this trial support the conclusion that a new dentifrice formulation containing pyrophosphate , tripolyphosphate and a copolymer , in a 0.243 % sodium fluoride/silica base , effectively removes extrinsic tooth stain OBJECTIVES This study aim ed to evaluate the stain removing/controlling properties of a whitening dentifrice and a stain controlling system , in a parallel group , multiple use study . METHODS Subjects ( 63 ) , were stratified according to baseline stain scores and r and omly allocated to a group , A ( st and ard dentifrice ) , B ( whitening/stain removing dentifrice ) or C ( whitening/stain removing dentifrice , tooth polish , tooth polisher and whitening/stain removing mouthwash ) . At each attendance , extrinsic stain was scored blind by a trained and calibrated examiner using the Shaw and Murray Stain Index , under constant lighting conditions . In addition , whiteness was measured using a colorimeter . RESULTS The toothpaste regimens were well balanced at baseline ( p=0.811 ) . At 4 weeks , Regimens B and C had significantly less stain than A ( p<0.05 ) . Lower stain values were maintained/reduced for regimens B and C by week 6 , with changes from baseline significantly greater than for Regimen A. When lightness was assessed by colorimeter , Regimen C was also found to be significantly whiter than Regimen A ( p<0.05 ) . CONCLUSIONS It was concluded that both whitening regimens had a significant effect on reducing tooth staining and improving whiteness over the 6 week time period BACKGROUND Extrinsic staining of teeth is considered to be unsightly and a number of ' whitening ' toothpastes have been formulated to inhibit or remove such tooth discoloration . The aim of this study was to compare the stain prevention of two toothpastes . METHOD The study was a single-blind , r and omised , placebo-controlled , crossover design , balanced for residual effects involving 24 healthy dentate volunteers . The treatments were as follows : ( 1 ) a whitening toothpaste product , ( 2 ) an experimental toothpaste formulation and ( 3 ) water . For each 4-day rinse period , subjects were rendered stain free on the teeth and tongue . Approximately on the hour from 09:00 to 16:00 hours , subjects rinsed with chlorhexidine mouth rinse for 1 min followed by warm black tea for 1 min . The treatment interventions were at 09:00 and 16:00 hours and before the chlorhexidine rinse . The toothpastes were rinsed as 3 g/10 ml water slurries and water as a 10 ml rinse each for 2 min . On day 5 , subjects were scored for tooth and tongue stain intensity and area , and the product of these was calculated . The washout period was at least 9 days . RESULTS Treatment differences for the teeth were highly significant but not for the tongue . Paired contrasts for tooth stain intensity , area and product were mostly all significantly in favour of reduced staining by the experimental formulation compared with water and the whitening product . There were no significant differences between water and the whitening product . CONCLUSIONS Using a forced dietary staining method , the data support a tooth stain-inhibitory/-removal action for the experimental formulation , but not the whitening product OBJECTIVE This r and omized controlled clinical trial was conducted to determine the effectiveness and safety of a new whitening dentifrice . METHODS One hundred eighty-two qualifying subjects were r and omly assigned to either a whitening dentifrice group ( Arm & Hammer Truly Radiant Toothpaste ) , a negative control dentifrice group ( Colgate Cavity Protection Toothpaste ) , or a positive control dentifrice group ( Crest 3-D White Radiant Mint Toothpaste ) and were instructed to brush twice daily with their assigned dentifrice for six weeks . Extrinsic tooth stain was assessed using a Modified Lobene Stain Index ( MLSI ) and tooth shade was assessed using the VITA Classic Shade Guide at baseline and after five days and two , four , and six weeks of dentifrice use . Safety was monitored by clinical examinations and panelist assessment at each evaluation period . RESULTS The Arm & Hammer Truly Radiant group showed a statistically significant improvement from baseline in mean composite MLSI and VITA shade at each examination period ( p < 0.0001 ) . Significant improvements on day 5 progressively increased with increasing duration of product use . By week 6 , there was a 45.4 % reduction in stain and a 2.08 improvement in tooth shade . The between-group comparison revealed that Truly Radiant toothpaste was significantly more effective than both the negative and positive control dentifrices for these parameters ( p < 0.0001 ) at each exam time . CONCLUSION This study showed that the new dentifrice formulation is safe and effective on stain removal and tooth whitening |
12,970 | 22,032,806 | Unidimensional pain assessment tools were most frequently used pain assessment tools , with multidimensional tools used less often , despite the multifaceted and complex nature of burn pain .
The review highlights the lack of consistency of pain assessment tool use in r and omized clinical trials with respect to managing burn pain . | INTRODUCTION Pain continues to be an ongoing issue of concern in adult burn patients .
Inadequate pain assessment hinders meaningful research , and prevents the optimal management of burn pain .
The objective of this study was to examine the content of existing research in burn pain with the frequency and context of pain assessment tool use in r and omized clinical trials in order to further inform their use for future research ers and clinicians . | This study sought to compare the analgesic efficacy and safety of patient controlled intra-nasal ( PCIN ) fentanyl with oral morphine for procedural wound care in burns patients . A r and omised double-blind placebo controlled , two period , two-treatment crossover trial was conducted within the Burns Unit of a major teaching hospital in Perth , Western Australia . Patients requiring identical wound care procedures on two consecutive mornings ( and not prescribed intravenous analgesia ) were r and omised to receive either PCIN fentanyl with oral placebo or oral morphine with intranasal placebo on 1 day , followed by the alternate active drug on the following day . Twenty-six patients ( 22 males ) , aged between 18 and 69 years ( 35.5 + /- 12.4 years ) , with total body surface burns ( TBSA ) range 1 - 25 % ( 6.9 + /- 4.5 ) , indicated their level of pain on a 10 point ( 0 - 10 ) numeric scale at various time periods before , during and after the procedure . A mean total dose of 1.48 + /- 0.57 microg/kg of PCIN fentanyl and 0.35 + /- 0.12 mg/kg of oral morphine was administered . No statistically significant difference was found between the pain scores recorded for patients during the procedure with PCIN fentanyl compared to that with oral morphine ( mean difference = -0.75 , 95 % CI = -1.97 to 0.47 , P = 0.22 ) . Two patients experienced hypotension during the procedure -- both had received active oral morphine . No patients experienced respiratory depression or a significant drop in oxygen saturation . There were four episodes ( in three patients ) where ' rescue analgesia ' for severe pain was required -- two episodes involving oral morphine and two involving PCIN fentanyl . It was concluded that PCIN fentanyl is similar in efficacy and safety to oral morphine for relief of procedural wound care pain in burns patients A prospect i ve study was design ed to compare two psychological support interventions in controlling peri-dressing change pain and anxiety in severely burned patients . Thirty patients with a total burned surface area of 10 - 25 % , requiring a hospital stay of at least 14 days , were r and omised to receive either hypnosis or stress reducing strategies ( SRS ) adjunctively to routine intramuscular pre-dressing change analgesia and anxiolytic drugs . Visual analogue scale ( VAS ) scores for anxiety , pain , pain control and satisfaction were recorded at 2-day intervals throughout the 14-day study period , before , during and after dressing changes . The psychological assistance was given on days 8 and 10 after hospital admission . The comparison of the two treatment groups indicated that VAS anxiety scores were significantly decreased before and during dressing changes when the hypnotic technique was used instead of SRS . No difference was observed for pain , pain control and satisfaction , although VAS scores were always better in the hypnosis group . The study also showed that , overall , psychological support interventions reduced pain and increased patient satisfaction . These results confirm the potential benefits of psychological assistance during dressing changes in burned patients This prospect i ve study evaluated the efficacy and safety of IV ibuprofen for the reduction of fever and treatment of pain in patients with thermal burn injury . A total of 61 patients with second- and /or third-degree thermal burns covering > 10 % TBSA were r and omly assigned in a 2:1 ratio to receive either 800 mg IV ibuprofen or placebo every 6 hours for 120 hours ( 5 days ) . Antipyretic medications were restricted during the first 24 hours of the study , but analgesics were allowed throughout . The primary efficacy endpoint was area under the curve for temperature ( AUC-T ° ) within the first 24 hours of treatment . After 24 hours of dosing , there was a significant reduction in temperature in patients who received IV ibuprofen compared with those who received placebo ( P = .008 ) . The temperature remained reduced over the entire 120-hour dosing period in the patients who received IV ibuprofen , although the difference beyond 24 hours did not reach statistical significance . Because of enrollment of patients unable to perform self- assessment s of pain , an inadequate number of patients were enrolled to detect differences in pain scores . There was no significant difference in the incidence of serious adverse events . Fever was reduced significantly by IV ibuprofen in burn patients over the initial 24-hour dosing period and remained reduced throughout the dosing period . Exposure to the maximum daily recommended dose of 3200 mg ( 800 mg every 6 hours ) for a total of 120 hours ( 5 days ) was well tolerated This study tested the efficacy of 2 brief cognitive interventions in supplementing regular medical treatment for pain during burn dressing change . Forty-two burn in patients were r and omly assigned to 3 groups : sensory focusing , music distraction , and usual care . Patients reported pain , pain relief , satisfaction with pain control and pain coping strategies . The sensory focusing group reported greater pain relief compared to the music distraction group and a reduction in remembered pain compared to the usual care group , although group differences were not observed on serial pain ratings . In addition , after controlling for burn size and relevant covariates , regression analyses indicated that catastrophizing predicted pain , memory for pain , and satisfaction with pain control . Refinement of the sensory focusing intervention is warranted to reduce catastrophic thinking and improve pain relief Background : The adverse consequences of burn injuries include pain and psychological distress , which show bidirectional associations . However , much of the existing research has relied on global measures of distress that do not separate distinct symptoms of anxiety and depression . Purpose : The purpose is to assess the prospect i ve effects of anxiety and depression on pain and functional outcomes following burn injury . Methods : This article describes a 2-year cohort study in patients hospitalized for serious burn injuries ( assessment s at discharge and 6-month , 1-year , and 2-year follow-up ) . Linear mixed effects analyses were conducted to model anxiety and depression ’s unique longitudinal effects ; at each time point , depressive and anxiety symptoms were studied as predictors of subsequent changes in pain , fatigue , and physical function . Results : When studied in separate prediction models , both depression and anxiety were strong prospect i ve predictors of greater pain , more fatigue , and physical dysfunction at the subsequent time point ( ps<.01 ) . However , when both were included in a single model to study their unique effects , depressive symptoms ( but not anxiety ) emerged as a signfiicant predictor of subsequent increases in pain and reductions in physical functioning , whereas anxiety ( but not depression ) predicted subsequent elevations in fatigue . Conclusions : These findings suggest potentially distinct effects of depression and anxiety and imply that assessment and early treatment of both depressive and anxiety symptoms may help improve a broad range of long-term pain-related outcomes following burn inury & NA ; This r and omised , double‐blind , placebo‐controlled trial assessed the efficacy and tolerability of pregabalin to alleviate the neuropathic component of moderate to severe burn pain . Patients aged 18 to 65 years admitted to a burns unit with a 5 % or greater total body surface area burn injury were screened to participate in the trial . Using the Neuropathic Pain Scale ( NPS ) , patients scoring 4 or higher on ‘ hot ’ pain or ‘ sharp ’ pain were invited to participate . Consenting patients were r and omly assigned to receive pregabalin or placebo for 28 days with individual dose titration commencing at 75 mg twice daily to a maximum pregabalin dose of 300 mg twice daily . The primary outcome measure was the patients ’ daily response to the sharp and hot pain of the NPS . Secondary outcome measures included the remaining elements of the NPS , daily opioid requirement , length of hospital stay , pain at 6 months , and side effects of nausea , vomiting , drowsiness and giddiness . For patients administered pregabalin , the primary outcome measures hot ( P = .01 ) and sharp ( P = .04 ) pain were significantly reduced compared with those in patients administered placebo . Secondary outcome measures of itch , unpleasantness , surface pain , and procedural pain were significantly lower ( P < .05 ) in the pregabalin group . Adverse effects were uncommon , with no difference between the treatment groups . There was no significant difference between the pregabalin and placebo treatment groups with respect to opioid consumption , duration of hospital stay , or pain at 6 months . Pregabalin was efficacious and well tolerated in patients after severe burn injury and whose pain was characterised by features of acute neuropathic pain . In this study , pregabalin was well tolerated and significantly reduced several elements of the neuropathic pain scale including hot pain , unpleasantness of the pain , surface pain , and itch , and also significantly reduced procedural pain Pain and anxiety are well-documented problems during the rehabilitation of patients with burns . This study examined the effect of music on anxiety and pain during range of motion . Eleven subjects with partial-thickness or deeper burns were r and omly assigned to a control group ( without music intervention ) or experimental group ( with music intervention ) . Vital signs , pain , and anxiety were recorded before and after treatments . There was no difference in pretest and posttest anxiety across the groups ; however , there was a difference in anxiety between the groups . Conversely , there was a difference in pretest and posttest pain across the groups but no difference in pain between the groups . Results showed no significant reduction in anxiety and pain during therapy with music relaxation . Limitations included nonhomogenous groups , small sample size , potentially unrepresentative sample , variation in exercise protocol , and small musical selection . Further research is recommended Burn patients must often endure intense pain during their regular dressing changes . The aim of the present study was to investigate the therapeutic effect of rapid induction analgesia ( RIA ) on resting and procedural pain , anticipatory anxiety , relaxation levels and medication consumption in 30 hospitalized burn patients . Patients rated levels of pain and relaxation for four burn care sessions . RIA was conducted twice on 15 patients , whereas dressing changes proceeded as usual in 15 control patients . When asked to recall pain during the dressing changes , patients remembered an experience which was worse in its entirety than the average of spot ratings taken during the burn care procedure . However , self-reported ratings of the sensory and affective components of pain decreased significantly during and after RIA , particularly in patients who became readily absorbed , and relaxation increased during burn care . Anticipatory anxiety decreased before dressing changes in the RIA group , and analgesic intake decreased between treatment sessions . The promising outcome of this study confirms RIA as a viable adjunct to narcotic treatment for pain control during burn care The purpose of this single-blinded r and omized clinical trial was to determine whether therapeutic touch ( TT ) versus sham TT could produce greater pain relief as an adjunct to narcotic analgesia , a greater reduction in anxiety , and alterations in plasma T-lymphocyte concentrations among burn patients . Therapeutic touch is an intervention in which human energies are therapeutically manipulated , a practice conceptually supported by Rogers ' ( 1970 ) theory of unitary human beings . Data were collected at a university burn centre in the south-eastern United States . The subjects were 99 men and women between the ages of 15 and 68 hospitalized for severe burns , and they received either TT or sham TT once a day for 5 days . Baseline data were collected on day 1 , data were collected before and after treatment on day 3 , and post-intervention data were collected on day 6 . Instruments included the McGill Pain Question naire , Visual Analogue Scales for Pain , Anxiety and Satisfaction with Therapy , and an Effectiveness of Therapy Form . Blood was drawn on days 1 and 6 for lymphocyte subset analysis . Medication usage for pain in mean morphine equivalents , and mean doses per day of sleep , anxiety and antidepressant medications were recorded . Subjects who received TT reported significantly greater reduction in pain on the McGill Pain Question naire Pain Rating Index and Number of Words Chosen and greater reduction in anxiety on the Visual Analogue Scale for Anxiety than did those who received sham TT . Lymphocyte subset analyses on blood from 11 subjects showed a decreasing total CD8 + lymphocyte concentration for the TT group . There was no statistically significant difference between groups on medication usage Abstract Benzodiazepines are commonly used to supplement opioid analgesics in treating procedural pain during the treatment of major burn injuries . To date , no study has investigated whether benzodiazepines actually have an analgesic or anxiolytic effect in such circumstances . Seventy‐nine patients admitted to a major regional burn center were r and omly assigned to groups that received 1 mg of lorazepam or a placebo in addition to their st and ard opioid analgesics . A strong analgesic effect of lorazepam was not observed when treatment groups were compared independent of their baseline pain ratings . However when patients who had high baseline pain were compared , lorazepam result ed in a significant reduction in pain ratings ( adjusted post‐treatment VAS mean score=54.28 ; adjusted control VAS mean score=69.06 ) . Trait anxiety did not predict those patients who had an analgesic effect with lorazepam , but state anxiety did prove to be a covariate with visual analogue score decreases in pain reports The authors examined ratings on a scale of pain-related anxiety in 173 burn patients in three groups : patients with small burns , patients with moderate burns and patients with extensive burns . The data suggest a greater degree of anxiety during procedures and before procedures in the burn patients with extensive burns than in burn patients with small and moderate burns . This study introduces a novel measure of pain-related anxiety in clinical burn patients , the abbreviated Burn Specific Pain Anxiety Scale ( BSPAS ) , which showed a high degree of reliability . The alpha coefficients were high for the BSPAS subscales Pain management during burn dressing changes is a critical part of treatment in acute burn injuries . Although several treatment options have been suggested , it is still a challenge in a clinical setting . This study is aim ed at finding out an ideal analgesic , sedative and /or anxiolytic combination that would minimise the unwanted effects of ketamine . A total of 24 patients , with burns up to 20 - 50 % of total body surface area ( TBSA ) , were included in the study and r and omly divided into three groups . In group I , 2 mg kg(-1 ) ketamine was administered . In group II , 1 mg kg(-1 ) tramadol was administered and 30 min later , 1 microg kg(-1 ) dexmedetomidine and 2 mg kg(-1 ) ketamine was administered . In group III , 1 mg kg(-1 ) tramadol was applied and 30 min later , 0.05 mg kg(-1 ) midazolam and 2 mg kg(-1 ) ketamine was administered . The evaluation was performed with cardiopulmonary monitoring , sedation and visual analogue pain scores and overall patient satisfaction . Any adverse effects of ketamine were recorded . The results showed that group II had better outcomes with respect to pain management during dressing changes . As a conclusion , the use of the combination of ketamine , tramadol and dexmedetomidine was found to be a good treatment option for the prevention of the procedural pain suffered by adult patients during dressing changes BACKGROUND Pain is a major issue for patients with severe burn . High dose intravenous opioids form the mainstay of procedural burns pain management ; however it was suggested that intravenous lidocaine assists with minimising the pain experience . This study aim ed to evaluate whether intravenous lidocaine improved analgesic efficacy and decreased opioid consumption during a burn wound care procedure . METHODS A prospect i ve double-blind r and omized crossover study compared intravenous lidocaine versus placebo alongside patient controlled analgesia ( PCA ) in 45 patients with severe burn undergoing wound care procedures ( i.e. dressing change±debridement ) on two consecutive days . Subjects were r and omised to either the intervention or control condition on the first dressing day , and received the alternate condition on the second dressing day . During the intervention condition , subjects received lidocaine of 1.5 mg/kg/body weight followed by two boluses of 0.5 mg/kg at 5-min intervals followed by a continuous infusion . During the control condition , 0.9 % sodium chloride was administered at an equivalent volume , dose and rate to that of lidocaine . Primary end points included pain intensity as measured by verbal rating scale ( VRS ) , time to rescue analgesia , opioid requests and consumption and overall anxiety and level of satisfaction . RESULTS Changes in the VRS score was significantly lower for lidocaine [ difference ( 95 % CI)=0.36 ( 0.17 - 0.55 ) ] as compared to placebo . However , there were no significant clinical or statistical differences regarding the effects of lidocaine and placebo on opioid requests and consumption , anxiety or level of satisfaction during the first and second dressing procedures . CONCLUSIONS In this study , the clinical benefit of intravenous lidocaine for pain relief during burn wound dressing changes in terms of overall pain scores and opioid consumption was unremarkable . Further investigations using different lidocaine regimes for the management of procedural burn pain are warranted PURPOSE R and omized clinical trials can provide strong evidence regarding effective treatment options . The quality of reporting and the type of outcome measures used are important when judging whether results justify change in clinical practice . The aim of this study was to assess the quality of reporting of r and omized clinical trials related to treatment of upper-extremity disorders , published in 4 h and surgical and orthopedic journals during an 11-year period , and assess the type of outcome measures used in the trials . METHODS Eligible articles were identified by review ing all abstract s published in the 4 journals from 1992 through 2002 . The quality of reporting was assessed by a modified Jadad scale that consisted of 3 items ( r and omization , blinding , and withdrawals/dropouts ) . A higher score ( 0 - 5 ) indicated higher quality . The outcome measures were classified according to the International Classification of Functioning , Disability and Health into the levels of body function and structure , activity , and participation . RESULTS Of 92 articles reporting r and omized clinical trials , 40 articles described appropriate r and omization method that implied they were truly r and omized studies , 31 articles did not describe the r and omization method , and 21 articles ( 23 % ) described inappropriate r and omization methods . Double or single blinding was reported in 33 articles . Absence or description of withdrawals/dropouts was shown in 77 articles . The median quality score calculated for all 92 articles was 2 ( range , 0 - 5 ) points . The median score for the 28 articles published 1992 through 1996 was 1 ( range , 0 - 5 ) points and for the 64 articles published from 1997 through 2002 was 3 ( range , 0 - 5 ) points . All trials used outcome measures on body function and structure level ; 41 % used measures of activity and /or participation . CONCLUSIONS There is a need to improve the quality of reporting of upper-extremity r and omized clinical trials and to increase the use of outcome measures covering different aspects of disability A double‐blind controlled study was performed to assess the efficacy and safety of patient‐controlled analgesia in burn patients . This method was compared with conventional analgesic therapy consisting of intermittent intravenous morphine injections . Twenty‐four adult patients hospitalised for burn injuries participated in the study . The McGill Pain Question naire , visual analogue scales and verbal‐numeric scales were administered at regular intervals to measure various components of the patients ' pain experience , degree of pain relief , anxiety levels , adverse side effects and overall treatment efficacy . Although statistical significance was found in only one measure , the results suggested better pain control in patients who were administered morphine by patient‐controlled analgesia as compared with intermittent injections . Analysis of the side effects showed no difference between the groups . The amount of morphine administered over the trial period was also similar for the two groups but considerable interpatient variability was seen . Although further research is needed to determine the conditions for optimal use of patient‐controlled analgesia , it is concluded that it is a safe , effective and improved method for controlling pain in selected burn patients Surgical nurses from five Dutch general hospitals participated in a continuing education program on pain assessment and management . A pretest-posttest controlled intervention study revealed that the program led to an increase in the quality of activities relevant to taking pain histories . Although this increase in quality was most apparent 1 month after the program , it was still observable 6 months after the program . There were , however , no effects on the number of activities relevant to taking pain histories , or on the number of nurses who used direct question ing as a method to determine pain . There may be several explanations for these results , including nurses ' limited openness to new approaches , a lack of support from physicians and nurse superiors , and that program items were not translated into ward policy Thirty-two patients hospitalized for the care of major burns were r and omly assigned to groups that received hypnosis , lorazepam , hypnosis with lorazepam , or placebo controls as adjuncts to opioids for the control of pain during dressing changes . Analysis of scores on the Visual Analogue Scale indicated that although pain during dressing changes decreased over consecutive days , assignment to the various treatment groups did not have a differential effect . This finding was in contrast to those of earlier studies and is likely attributable to the low baseline pain scores of subjects who participated . A larger number of subjects with low baseline pain ratings will likely be necessary to replicate earlier findings . The results are argued to support the analgesic advantages of early , aggressive opioid use via PCA or through careful staff monitoring and titration of pain drugs The effects of teaching patients strategies for coping with the pain of an acute burn injury and its treatment were investigated . Twenty patients with comparable burn injuries and admitted to a Burn Center were r and omly assigned to either a control or experimental group . Experimental patients received systematic instruction on how to cope with the pain and stress of burn injury ; control patients received st and ard information and social support only . Results showed that experimental patients reported less pain and greater sense of psychological well-being and control over the outcome of their injuries than did control patients . Moreover , experimental patients went home , on the average , more than 1 week sooner than did control patients . The implication s of these findings for the improved care of patients with burn injuries and the economics of burn care are discussed OBJECTIVE To determine if topical administration of local anesthesia , applied to fresh skin-harvest sites , reduces pain and analgesic requirements after surgery . SUMMARY BACKGROUND DATA Nonopioid treatments for pain after therapeutic procedures on patients with burns have become popular because of the side effects associated with narcotics . The topical administration of local anesthesia originally offered little advantage because of poor epidermal penetration . METHODS This study compares 2 % lidocaine with 0.5 % bupivacaine or saline , topically applied after skin harvest , to determine what effect this may have on pain and narcotic use . Sixty patients with partial- or full-thickness burns to approximately 10 % to 15 % of their body were r and omly divided into three groups : group 1 received normal saline , group 2 had 0.5 % bupivacaine , and group 3 had 2 % lidocaine sprayed onto areas immediately after skin harvest . Blood sample s were subsequently obtained to measure concentrations of the local anesthetic . Hemodynamic variables after surgery , wake-up times , emetic symptoms , pain , and narcotic use were compared . RESULTS Higher heart rates were noted in the placebo group than in those receiving lidocaine or bupivacaine . No differences were noted in recovery from anesthesia or emetic symptoms . Pain scores were lower and 24-hour narcotic use was less in patients who received lidocaine . Plasma lidocaine levels were greater than bupivacaine at all time points measured . CONCLUSIONS Topical lidocaine applied to skin-harvest sites produced an analgesic effect that reduced narcotic requirements compared with patients who received bupivacaine or placebo . Local anesthetic solutions aerosolized onto skin-harvest sites did not affect healing or produce toxic blood concentrations Objectives : To test the analgesic efficacy of topical morphine on superficial burns within the emergency department by comparing pain scores , comfort ratings and analgesia taken by participants . Method : A placebo-controlled three-treatment r and omised controlled trial was undertaken . 59 participants were r and omly allocated to receive a dressing containing Intrasite gel and morphine sulphate , Intrasite gel and water or the conventional Jelonet dressing . The study design enabled double-blinding between the two Intrasite gel treatments . Results : 49 participants were included in the final analysis as 10 were lost to follow-up . No significant differences were observed between the pain scores or comfort ratings of the three treatments . Participants receiving Jelonet and the placebo reduced their pain scores by the greatest amount overall . However , participants receiving morphine were the only group to reduce pain scores by > 20 mm on two consecutive time intervals ( 2 and 6 h ) . At 12 h the morphine group reported the highest pain scores . Only 4/15 participants receiving topical morphine administered additional analgesia compared with 12/17 receiving the Jelonet dressing and 6/17 receiving Intrasite and water ( p = 0.055 ) . However , when all analgesia was taken into account , the morphine group was administered the greatest amount . Overall , the placebo group reported their dressings to be the most comfortable and took the least amount of analgesia . Minor adverse reactions included itching , burning and a rash . No serious adverse reactions were reported . Conclusions : Topical morphine sulphate does not seem to be as effective when used for the pain associated with superficial burns as when used for the pain associated with chronic inflammatory wounds . ( The European Clinical Trials Data base number for this study is 2005 - 003285 - 42 . BACKGROUND Pain arising in burns sufferers is often severe and protracted . The prospect of a dressing change can heighten existing pain by impacting both physically and psychologically . In this trial we examined whether pre-procedural virtual reality guided relaxation added to patient controlled analgesia with morphine reduced pain severity during awake dressings changes in burns patients . METHODS We conducted a prospect i ve r and omized clinical trial in all patients with burns necessitating admission to a tertiary burns referral centre . Eligible patients requiring awake dressings changes were r and omly allocated to single use virtual reality relaxation plus intravenous morphine patient controlled analgesia ( PCA ) infusion or to intravenous morphine patient controlled analgesia infusion alone . Patients rated their worst pain intensity during the dressing change using a visual analogue scale . The primary outcome measure was presence of 30 % or greater difference in pain intensity ratings between the groups in estimation of worst pain during the dressing change . FINDINGS Of 88 eligible and consenting patients having awake dressings changes , 43 were assigned to virtual reality relaxation plus intravenous morphine PCA infusion and 43 to morphine PCA infusion alone . The group receiving virtual reality relaxation plus morphine PCA infusion reported significantly higher pain intensities during the dressing change ( mean=7.3 ) compared with patients receiving morphine PCA alone ( mean=5.3 ) ( p=0.003 ) ( 95 % CI 0.6 - 2.8 ) . INTERPRETATION The addition of virtual reality guided relaxation to morphine PCA infusion in burns patients result ed in a significant increase in pain experienced during awake dressings changes . In the absence of a vali date d predictor for responsiveness to virtual reality relaxation such a therapy can not be recommended for general use in burns patients having awake dressings changes Postoperative pain from split skin donor sites is often more intense than the pain at the grafted site . In this prospect i ve , r and omized , double-blind study we assessed the efficacy of a continuous fascia iliaca compartment block ( FICB ) in reducing the pain at the thigh donor site . Twenty patients , with a total burn surface area of 16 % ± 13 % ( mean ± sd ) were r and omized 1:1 to receive either ropivacaine 0.2 % or saline 0.9 % . All patients received a general anesthesic followed by preincision continuous FICB with 40 mL of the r and omized solution , then an infusion of 10 mL/h of either ropivacaine or saline until the first dressing change ( 72 h later ) . Postoperative analgesia consisted of propacetamol 2g/6h , IV patient-controlled analgesia of morphine chlorhydrate ( 2 mg/mL ) , and morphine hydrochlorate 0.5 mg/kg PO once 60 min before first dressing change . The visual analog scale ( VAS ) scores were compared using the Mann-Whitney U-test preoperatively , 24 and 48 h postoperatively , and during the first dressing change . The cumulative morphine consumption was compared with repeated- measures analysis of variance followed by Scheffé ’s method if indicated . Patients with continuous FICB had significantly reduced postoperative morphine consumption at all time points ( 23 ± 20 versus 88 ± 29 mg after 72 h , study versus control groups , respectively ; P < 0.05 ) . In both groups , VAS scores remained low but were only significantly lower for patients with continuous FICB during the first dressing change ( 3 [ 1 ] versus 7 [ 3 ] ; median [ interquartile range ] ; P < 0.05 ) . We conclude that continuous FICB is an efficient method for diminishing pain at the thigh donor site . ( 250 words Research has indicated that analgesics alone do not adequately relieve pain for 75 % of patients with burns . The purpose of this study was to determine the effects of a distraction therapy , in which videos were used in combination with administration of analgesics , on intensity and quality of pain and on levels of anxiety in adults during burn dressing changes . The sample consisted of 17 patients who were r and omly assigned to the treatment or the control group . The treatment group viewed video programs that were composed of scenic beauty accompanied by music . Each was asked to score his or her present pain intensity and pain rating index with the McGill question naire and anxiety with the Spielberger question naire before and after the dressing change . A nested general linear model using the " F " test in multiple regression analysis was adjusted for age , percent partial-thickness burn , and choice of topical agent demonstrated that the use of videos during the dressing changes significantly reduced pain and anxiety : present pain intensity ( F = 8.69 ; p = 0.01 ) , pain rating index ( F = 5.57 ; p = 0.03 ) , anxiety ( F = 9.10 ; p = 0.01 ) . It is recommended that the use of pain medication be augmented by use of videos during burn dressing changes The burn specific pain anxiety scale ( BSPAS ) is a nine-item self-report scale for the assessment of pain-related and anticipatory anxiety in burned patients . This paper describes a study design ed to explore the psychometric properties of the scale . The study used 35 burned patients hospitalized in Rotterdam and Groningen , The Netherl and s , to confirm the internal consistency of the instrument and provide an assessment of its validity . The alpha coefficient was high : 0.94 . The BSPAS correlated statistically significantly with the STAI-S , procedural pain , non-procedural pain , and nurses ' visual analog observation ratings of tension OBJECTIVE Little is known about how pain and depression after burn injury may influence long-term outcomes such as physical functioning . This prospect i ve study examined associations between pain , depression , and physical functioning in a sample of burn injury survivors . DESIGN AND PARTICIPANTS Question naires assessing pain , depression , and physical functioning were completed by 64 ( 52 % of original sample ) adult burn survivors shortly after discharge from burn care and at 1- and 2-year follow-ups . RESULTS Pain and physical functioning improved over the 2 years of the study , whereas depression levels were stable . Pain and depression were associated with poorer physical functioning over time , but associations varied according to the time span under consideration . Also , the association between pain and physical functioning was strongest among persons with higher depression scores . CONCLUSIONS Pain and depression may contribute independently to compromises in physical functioning . The co-occurrence of pain and depression represents even greater risk for reduced physical functioning over time among burn survivors |
12,971 | 15,752,957 | An early effect of alcohol leading to a reduction BP ( in the hours after exposure ) and a later effect ( next day ) of raising BP led to smaller differences in the net effect of alcohol on BP when ambulatory BP monitoring measurements were compared with casual office- or clinic-based measurements .
These findings indicate that the timing of BP measurements after alcohol intake has a substantial effect on the magnitude and perhaps even the direction of BP change | Numerous epidemiologic investigations have found an association between moderate intake of alcohol and increased blood pressure ( BP ) .
However , in controlled clinical studies that directly tested the effects of alcohol intake on BP , findings are inconsistent , perhaps because of differences in duration of alcohol use and the timing of BP measurements . | Office blood pressure ( OBP ) , ambulatory blood pressure ( ABP ) , and vascular reactivity were measured in 12 normotensive ' social ' drinkers ( mean alcohol consumption of 9.7 + /- 3.1 g/day ) after 4 days of alcohol consumption ( 1 g/kg/day ) and compared with the effects of an isocaloric substitute ( sucrose , 1.75 g/kg/day ) or no intervention . Alcohol consumption did not affect OBP or 24-mean ABP but appeared to decrease nocturnal systolic and diastolic blood pressure soon after consumption . Although vascular reactivity did not differ between the groups , the blood pressure rise in response to isometric exercise tended to be lower following alcohol . Thus , short-term alcohol ingestion by normotensive ' social ' drinkers does not increase office or ambulatory blood pressure A direct pressor effect of alcohol is proposed as the basis for the association between regular alcohol consumption and an increase in blood pressure found in population studies . To examine this further , a r and omized controlled crossover trial of the effects of varying alcohol intake on blood pressure in 46 healthy male drinkers was conducted . From an average of 336 ml of ethanol per week , alcohol consumption was reduced by 80 % for 6 weeks by drinking a low alcohol content beer alone . This reduction was associated with a significant reduction in systolic and diastolic blood pressure ( p less than 0.001 and p less than 0.05 respectively ) . The mean difference in supine systolic blood pressure during the last 2 weeks of normal or low alcohol intake was 3.8 mm Hg , which correlated significantly with change in alcohol consumption ( r = 0.53 , p less than 0.001 ) . Reduction of alcohol intake also caused a significant decrease in weight ( p less than 0.001 ) . After adjustment for weight change , an independent effect of alcohol on systolic but not diastolic blood pressure was still evident , with a 3.1 mm Hg fall predicted for a decrease in consumption from 350 ml of ethanol equivalent per week to 70 ml per week ( p less than 0.01 ) . Systolic blood pressure rose again when normal drinking habits were resumed . These results provide clear evidence for a direct and reversible pressor effect of regular moderate alcohol consumption in normotensive men and suggest that alcohol may play a major role in the genesis of early stages of blood pressure elevation The effect of alcohol on blood-pressure was studied in 16 men with hypertension who regularly drank up to 80 g of alcohol daily . Antihypertensive treatment was stopped 2 weeks before the men were admitted to hospital for a 7-day study . Blood pressure remained high in 8 patients who continued their regular alcohol consumption up to the fourth day after admission . In the next 4 days no alcohol was taken and diastolic and systolic blood pressures fell significantly . 8 other patients had no alcohol for the first 3 days after admission , but they resumed alcohol consumption from day 4 to 7 . In these patients , blood pressure fell slightly after admission . Re introduction of alcohol produced statistically significant increases in both systolic and diastolic pressures . This study demonstrated a pressor effect of alcohol in patients with hypertension and confirms the link between alcohol and blood-pressure reported in population studies . The mechanism of alcohol-induced hypertension is uncertain and is more likely to be due to an effect of alcohol rather than to the pressor response produced by alcohol withdrawal Fifty-four untreated , mildly hypertensive men whose daily alcohol consumption was > or = 28 ml ethanol and who drank at least 4 times per week took part in a r and omized , controlled crossover trial . The purpose of the trial was to test the effects of alcohol reduction on blood pressure . After a 2-week familiarization period , the participants were assigned to either a reduced alcohol drinking group or a usual drinking group for 3 weeks ( experimental period 1 ) . The situation was then reversed for the next 3 weeks ( experimental period 2 ) . The participants were requested to limit their daily alcohol consumption to zero or reduce it as much as possible for the reduced alcohol consumption period . The self-reported alcohol consumption was 56.1 + /- 3.6 ( SEM ) ml/day during the usual alcohol drinking period and 26.1 + /- 3.0 ml/day during the period of reduced alcohol consumption . Systolic and diastolic blood pressures in the intervention group were found by analysis of variance to be significantly lower ( 2.6 - 4.8 and 2.2 - 3.0 mm Hg , respectively ) than those in the control group during experimental period 2 for systolic blood pressure and experimental period 1 for diastolic blood pressure . Significant ( 3.6 mm Hg ) and nonsignificant ( 1.9 mm Hg ) decreases in systolic and diastolic blood pressure , respectively , were observed . The method of Hills and Armitage was used , reducing ethanol in daily alcohol consumption by 28 ml . The lowering effect of reduced alcohol consumption on blood pressure was independent of changes in salt consumption , which were estimated by 24-hour urine collection and body weight . ( ABSTRACT TRUNCATED AT 250 WORDS 44 men with treated essential hypertension who were moderate to heavy drinkers took part in a r and omised , controlled , crossover trial of the effects of alcohol intake on blood pressure . Usual antihypertensive treatment was maintained throughout 6 weeks of normal drinking and 6 weeks of drinking only a low-alcohol beer . Self-reported changes in alcohol consumption ( mean [ SEM ] from 452 [ 30 ] ml ethanol/week during normal drinking to 64 [ 8 ] ml/week while drinking the low-alcohol beer ) were confirmed by biochemical measurements . Mean systolic and diastolic blood pressures were significantly lower during the last 2 weeks of the low-alcohol period than during the normal-alcohol period , the mean difference in the supine readings being 5.0 ( 1.4 ) and 3.0 ( 0.9 ) mm Hg , respectively . Regression analysis suggested that reduction in alcohol intake contributed to the fall in both systolic and diastolic blood pressures independently of changes in weight . Thus , curtailing alcohol intake may lead to improved blood-pressure control and may reduce the need for antihypertensive drugs The vasodilation that follows acute alcohol intake is hard to conciliate with the high prevalence of hypertension detected in those persons who consume regular amounts of alcohol . In this experiment we examined early and late hemodynamic effects of acute administration of water and of 15 g , 30 g , and 60 g of alcohol in 40 normal men , aged 19 to 30 years , using 24-h ambulatory blood pressure monitoring ( ABPM ) . Mean systolic and diastolic blood pressures were each approximately 4 mm Hg lower during the period immediately after ingestion of 60 g ( v 0 g ) of ethanol , and were 7 and 4 mm Hg higher , respectively , at night . The day minus night differences displayed a dose-response curve both for systolic ( P < .001 ) and diastolic blood pressure ( P = .045 ) . Three subjects in the 60-g group had more than 50 % of nightly blood pressure loads in the hypertensive range against none in the remaining groups ( P < .01 ) . In conclusion , our findings suggest that acute alcohol intake elicits a biphasic hemodynamic response , causing , first , vasodilatation and , later , a pressor effect . The higher prevalence of hypertension in alcohol abusers seen in epidemiological surveys may be , in part , a result of measurements done in the period of transiently increased blood pressure during ethanol washout PURPOSE Restriction of alcohol intake is widely recommended in the treatment of hypertension . However , we have observed that alcohol may have biphasic effects on blood pressure in Japanese men with hypertension . METHODS Hypertensive men ( n = 34 ) who habitually drank alcohol were r and omly assigned to keep their drinking habits constant for 4 weeks , or to abstain ( or reduce alcohol intake to a maximum of 15 mL/day ) for 4 weeks in a crossover design . Amount of alcohol intake was recorded by each patient throughout the study . Office and 24-hour ambulatory blood pressure were measured at the end of both periods . RESULTS After alcohol restriction , mean ( + /-SD ) ethanol intake decreased from 66+/-26 mL/day to 11+/-10 mL/day . Office systolic blood pressure decreased slightly from 142+/-12 mm Hg to 139+/-11 mm Hg , and diastolic blood pressure decreased significantly from 95+/-7 mm Hg to 93+/-7 mm Hg in the low-alcohol period . Daytime systolic blood pressure fell by 3+/-9 mm Hg ( P < 0.05 ) , but nighttime systolic blood pressure rose by 4+/-9 mm Hg ( P < 0.05 ) with restriction of alcohol intake . Thus , average 24-hour blood pressure did not change , although 24-hour heart rate and day-night difference in blood pressure decreased significantly in the low-alcohol period . CONCLUSION In Asian men with hypertension , restriction of alcohol intake reduces daytime blood pressure but not night-time or 24-hour blood pressure Ten normal volunteers consumed 80 g of ethanol per day or abstained from ethanol for 4 consecutive days prior to measurements of blood pressure , heart rate , vascular responsiveness to noradrenaline ( NA ) and angiotensin II ( AII ) infusions and sympathetic responsiveness to isometric h and grip exercise in an open , r and om order , crossed study . Supine systolic and diastolic pressures and heart rates , and erect systolic pressures rose significantly following ethanol . Vascular responsiveness to NA infusions was reduced in all subjects following ethanol , while responses to AII infusions did not show a consistent pattern of change . Plasma renin activity , plasma NA and adrenaline concentrations , and concentrations of the NA metabolite 3,4 dihydroxyphenylethylene glycol ( DHPG ) did not significantly differ following ethanol and control treatments . The rise in plasma NA following 2 min isometric h and grip at 50 % of maximal effort was greater following ethanol ( 0.24 + /- 0.21 nM ) than control ( 0.12 + /- 0.10 nM ) but the difference did not reach statistical significance . The pressor effect of regular ethanol consumption and the reduced vascular reactivity to NA may both be the result of an increase in sympathetic activity that was not large enough to measurably alter resting plasma NA concentrations 1 . Forty‐four males with treated essential hypertension and a moderate‐to‐heavy alcohol intake participated in a r and omized controlled crossover trial of the effects of varying alcohol intake on blood pressure control . Usual antihypertensive therapy was maintained unchanged throughout Objectives The International Nifedipine GITS Study Intervention as a Goal in Hypertension Treatment ( INSIGHT ) showed , by means of office blood pressure measurements , that long-term treatment with nifedipine GITS is as effective as diuretics in preventing cardiovascular and cerebrovascular complications . However , since office blood pressure measurements reflect to a limited extent blood pressure outside the office , a side-arm INSIGHT study in which patients underwent both office measurement and 24 h ambulatory blood pressure monitoring was also performed . Design and methods The study had a r and omized , double-blind , parallel group design . After 4 weeks of placebo , mild-to-moderate essential hypertensive patients were r and omized to nifedipine GITS 30 mg or amiloride 2.5 + hydrochlorothiazide 5 mg for 3.1 years . Dose titration was performed by dose doubling and addition of atenolol 25–50 mg or enalapril 5–10 mg , or other drugs when needed . Analysis was carried out by intention-to-treat and included computation of 24 h , day and night ambulatory blood pressure and heart rate values . Additional analyses included computation of the trough-to-peak ratio and the smoothness index ( the ratio between the average of the 24-hourly blood pressure reductions after treatment and its st and ard deviation ) . Results A total of 151 patients were recruited and 149 were valid for analysis : 78 patients had 24 h ambulatory recordings both at baseline and during treatment and 134 during treatment . Office , 24 h and day and night blood pressures were all significantly and similarly reduced by both treatments . Office and ambulatory heart rate was left unchanged by diuretics , while it was slightly reduced by nifedipine . Median trough-to-peak ratios were always > 0.5 and superimposable between the two treatment groups . Similarly , smoothness indices of systolic and diastolic blood pressures were comparably high for nifedipine and diuretics , thus demonstrating a similar well-balanced antihypertensive response to both drugs . No significant differences were observed between the two treatment groups in the number of cardiovascular events ( 17 in the nifedipine-based and 26 in the diuretics-based treatment group ) . Conclusions In the INSIGHT study , the long-term antihypertensive effect on 24 h blood pressure and the cardiovascular protection of nifedipine was similar to that of diuretics Background and aims The Hypertension Optimal Treatment ( HOT ) study showed that when antihypertensive treatment reduces diastolic blood pressure well below 90 mmHg , there can be a further reduction of cardiovascular events , particularly myocardial infa rct ion , with no evidence of a J-shaped curve at lower pressures . Office measurement , however , gives no information about blood pressure outside the office . This paper describes a HOT sub study in which patients underwent both office measurement and 24 h ambulatory blood pressure monitoring . Methods The mean age of the sub study population was 62 ± 7 years . Sub study patients were treated for a median period of 2 years . All received the dihydropyridine calcium antagonist felodipine , while some also received an ACE-inhibitor , a beta-blocker or a diuretic . Average 24 h , day and night ambulatory blood pressure values were computed at baseline ( n = 277 ) and during treatment ( n = 347 ) : 112 patients had been r and omized to a target office diastolic blood pressure ⩽ 90 mmHg , 117 to ⩽ 85 mmHg and 118 to ⩽ 80 mmHg . Additional analyses included computation of : ( 1 ) trough-to-peak ratio and ( 2 ) the smoothness index ( the ratio between the average of the 24 hourly blood pressure reductions after treatment and its st and ard deviation ) . Results Taking the subgroup as a whole , baseline 24 h average blood pressures ( 146 ± 18/90 ± 10 mmHg ) were significantly and markedly lower than office blood pressures ( 170 ± 14/105 ± 3 mmHg , P < 0.01 ) . Office , 24 h , day and night blood pressures were all significantly reduced by treatment , but there was a smaller fall in ambulatory , than in office pressures . The between group differences in office blood pressure were smaller than those observed in the overall HOT sample . Between-group differences in 24 h blood pressure were even smaller . Trough-to-peak ratios and smoothness indices were lowest in the highest blood pressure target group and highest in the lowest blood pressure target group . Office and ambulatory blood pressures were similar in the groups r and omized to placebo ( n = 170 ) or acetylsalicylic acid ( n = 177 ) . Conclusion In conclusion , in the HOT study , treatment reduced not only office but also ambulatory blood pressure throughout the 24 h. The reduction was less marked for ambulatory than for office blood pressure 1 . Forty‐six healthy normotensive male drinkers participated in a r and omized , controlled , crossover trial to study the effects of varying alcohol intake on blood pressure A r and omised , controlled , single blind trial was conducted in office workers with mild hypertension ( systolic blood pressure ( SBP ) 140 to 180 mmHg , diastolic blood pressure ( DBP ) 90 to 110 mmHg ) to determine the effect of decreasing alcohol consumption . After a baseline examination , 50 male volunteers aged 30 to 59 were r and omised to two groups . Group A were told to abstain from or reduce alcohol consumption for two weeks , while group B were instructed to maintain their usual alcohol consumption . Complete records were obtained on 49 subjects . The daily alcohol consumption of groups A and B at baseline was similar , i.e. 71.9 ml and 72.5 ml of ethanol , respectively , and changed to 16.1 ml and 62.9 ml , respectively , during the experiment . After two weeks , group A were asked to resume their normal consumption whilst group B were asked to reduce or abstain ( phase II ) . However in view of a treatment period interaction , statistical analysis was confined to phase I. During phase I , group A , whose alcohol consumption had reduced , showed decreases of 5.8 and 7.1 mmHg in SBP during the the first and second weeks , respectively . In group B , these decreases were only 0.6 and 1.9 mmHg , respectively . The difference between the falls in SBP in groups A and B was significant ( P = 0.005 ) as judged by analysis of variance . The DBP also decreased , but there was no significant difference between the decreases in the two groups . Changes in gamma-glutamyl-transpeptidase , a biochemical marker of alcohol consumption , from the initial values to the end of phase I were significantly different in groups A and B. ( ABSTRACT TRUNCATED AT 250 WORDS To compare the influences of alcohol and salt intake on 24-h blood pressure ( BP ) , we studied short-term effects of repeated alcohol ingestion and dietary salt intake in hypertensive patients . Thirty-two Japanese men with mild to moderate essential hypertension ( 54 + /- 1 years old , mean + /- SE ) were examined . Sixteen patients were given alcohol ( 1 ml/kg ) with dinner for 7 d after a 7-d control period with an isocaloric beverage . Another group consisting of 16 age- and weight-matched patients consumed a low-sodium diet ( 25 mmol/d ) for 7 d , followed by a high-sodium diet ( 250 mmol/d ) for 7 d. Twenty-four-hour BP was measured at the end of each period . Average 24-h BP in the alcohol period ( 137 + /- 4/83 + /- 2 mmHg ) was similar to that in the control period ( 138 + /- 4/84 + /- 2 mmHg ) . However , BP in the alcohol period was significantly lower in the evening , but significantly higher in the morning than that in the control period . Heart rate increased for several hours after alcohol ingestion , result ing in a significant increase in 24-h heart rate ( 67 + /- 2 vs. 64 + /- 2 beats/min ) . Average 24-h BP was higher in the high salt period ( 144 + /- 4/89 + /- 4 mmHg ) than in the low salt period ( 135 + /- 3/85 + /- 3 mmHg , p < 0.05 ) . The pressor effect of high salt intake was sustained throughout the day and was associated with a decrease in 24-h heart rate ( 60 + /- 2 vs. 66 + /- 2 beats/min ) . In conclusion , short-term repeated intake of alcohol may have little effect on average 24-h BP while it causes an evening fall and a morning rise in BP , and high salt intake raises BP throughout the day . Alcohol consumption increases and salt loading decreases 24-h heart rate Normotensive male volunteers ( n = 8) either abstained from ethanol for 4 days or consumed 66 g of ethanol per day in an open , crossed , r and om order study . Mean arterial pressures rose by an average of 5.4 mmHg following the ethanol phase of the study ( P less than 0.001 ) . Plasma noradrenaline ( NA ) concentration was higher during ethanol ingestion ( P less than 0.01 ) , principally because of a significant reduction in NA clearance of -1.51 l min-1 m-2 ( P less than 0.05 ) . In contrast , NA spillover or release rates did not significantly differ between the two study periods . Total plasma calcium levels were significantly lower ( P less than 0.05 ) following the ethanol compared to the control period . These data do not appear to support the proposition that regular alcohol consumption raises blood pressure by producing a generalised increase in sympathetic activity |
12,972 | 25,919,147 | Positive expression was often correlated with adverse clinical characteristics , including disease stage and differentiation grade .
In summary , EMH expression was common in HNSCC patients and negatively influenced their prognosis . | Awareness increases that the tumor biology influences treatment outcome and prognosis in cancer .
Tumor hypoxia is thought to decrease sensitivity to radiotherapy and some forms of chemotherapy .
Presence of hypoxia may be assessed by investigating expression of endogenous markers of hypoxia ( EMH ) using immunohistochemistry ( IHC ) .
In this systematic review we investigated the effect of EMH expression on local control and survival according to treatment modality in head and neck cancer ( head and neck squamous cell carcinoma [ HNSCC ] ) . | PURPOSE To vali date the predictive impact of a hypoxia gene expression classifier in identifying patients with head and neck squamous cell carcinoma ( HNSCC ) having benefit from hypoxic modification of radiotherapy . PATIENTS AND METHODS Gene expressions were quantified from formalin-fixed , paraffin-embedded tumour biopsies of 323 HNSCC patients r and omized for placebo or nimorazole in conjunction with radiotherapy in the DAHANCA 5 study . Tumours were classified as either " more " or " less " hypoxic with a classifier constituting of 15 hypoxia responsive genes . The predictive impact was evaluated by analysing the response to nimorazole vs. placebo in terms of loco-regional tumour control ( LRC ) and disease-specific survival ( DSS ) in the two classified groups . RESULTS Hundred and fourteen patients ( 35 % ) were classified as having " more " hypoxic tumours . These patients had a significant benefit of hypoxic modification with nimorazole compared with placebo in terms of LRC ( 5-year actuarial values 49 % vs. 18 % ; p=0.001 ) and DSS ( 48 % vs. 30 % ; p=0.04 ) . " Less " hypoxic tumours had no significant effect of hypoxic modification ( LRC : 50 % vs. 44 % ; p=0.39 , DSS : 57 % vs. 51 % ; p=0.49 ) and generally an outcome , which was similar to " more " hypoxic tumours treated with nimorazole . In contrast to HPV-negative tumours , HPV-positive tumours had a substantially better outcome in response to radiotherapy , which was irrespective of hypoxic modification . CONCLUSIONS A predictive 15-gene hypoxia classifier could identify patients associated with improved outcome after combining radiotherapy with hypoxic modification and underlines the relevance of such therapy . The impact of the classifier was limited to HPV-negative tumours PURPOSE Tumor hypoxia is known to be associated with resistance to chemotherapy , radiotherapy , and poorer survival . Recently , it is shown that hypoxia induces the expression of hypoxia-inducible factor-1alpha and 2alpha ( HIF-1alpha and HIF-2alpha ) , which then up-regulates the expression of downstream genes such as carbonic anhydrase IX ( CA IX ) and vascular endothelial growth factor ( VEGF ) . EXPERIMENTAL DESIGN We examined the expression of HIF-1alpha , HIF-2alpha , CA IX , and VEGF by immunohistochemistry in nasopharyngeal carcinoma ( NPC ) biopsies from 90 consecutive patients recruited between 1994 and 1997 in a r and omized controlled trial of chemoradiation in locally advanced NPC and investigated their relationship with survival . RESULTS HIF-1alpha was expressed in 52 of 90 ( 58 % ) , HIF-2alpha in 6 of 89 ( 7 % ) , CA IX in 51 of 90 ( 57 % ) , and VEGF in 54 of 90 ( 60 % ) of tumors . Tumor HIF-1alpha expression correlated significantly with that of CA IX ( P = 0.008 ) and VEGF ( P = 0.003 ) . High tumor HIF-1alpha expression was associated with a trend for poor overall survival ( P = 0.06 ) . Tumors with a positive hypoxic profile ( defined as high expression of both HIF-1alpha and CA9 ) were associated with worse progression-free survival ( P = 0.04 ) . Tumors with both hypoxic and angiogenic profile ( defined as high VEGF expression ) were associated with a worse progression-free survival ( P = 0.0095 ) . CONCLUSION Overexpression of HIF-1alpha , CA IX , and VEGF is common in NPC , which is probably related to hypoxia up-regulated expression involving a HIF-dependent pathway , and is associated with poor prognosis . Targeting the hypoxia pathway may be useful in the treatment of NPC Hypoxia , a common feature of the microenvironment in solid tumors , is associated with resistance to radiotherapy , reduced therapeutic response , and a poorer clinical outcome . In head and neck squamous cell carcinomas ( HNSCC ) , the negative effect of hypoxia on radiotherapy can be counteracted via addition of hypoxic modification to the radiotherapy . To predict which patients harbor hypoxic tumors and would therefore benefit from hypoxic modification , clinical ly applicable methods for pretherapeutic hypoxic evaluation and categorization are needed . In this study , we developed a hypoxia classifier based on gene expression . Through study of xenograft tumors from human squamous cell carcinoma cell lines , we verified the in vivo relevance of previously identified in vitro derived hypoxia-induced genes . We then evaluated a training set of 58 hypoxia-evaluated HNSCCs to generate a gene expression classifier containing 15 genes . This 15-gene hypoxia classifier was vali date d in 323 patients with HNSCC r and omized for hypoxic modification or placebo in combination with radiotherapy . Tumors categorized as hypoxic on the basis of the classifier were associated with a significantly poorer clinical outcome than nonhypoxic tumors . This outcome was improved and equalized to the nonhypoxic tumors by addition of hypoxic modification . Thus , findings show that the classifier attained both prognostic and predictive impact , and its pretherapeutic use may provide a method to identify those patients who will benefit from hypoxic modification of radiotherapy BACKGROUND AND PURPOSE CA IX is suggested to be an endogenous marker of hypoxia in tumours like squamous cell carcinomas of the head and neck ( HNSCC ) . The aim of the present study was to investigate whether CA IX served as a prognostic factor for outcome in a large population of HNSCC and if CA IX was able to discriminate the tumours that did benefit from hypoxic modification with nimorazole . MATERIAL S AND METHODS Paraffin-embedded formalin-fixed pre-treatment tumour tissue was available from 320 of the 414 patients treated in the r and omized DAHANCA 5 protocol with primary radiotherapy+/-the hypoxic radiosensitizer nimorazole . CA IX was measured using immunohistochemistry and results were divided into four groups of CA IX expression : < 1 % , 1 - 10 % , 10 - 30 % and > 30 % of the tumour area with positive membrane staining . Locoregional control and disease-specific survival were used as endpoints . RESULTS Expression of CA IX was not correlated to any of the tumour or patient characteristics investigated . Furthermore , CA IX did not serve as a prognostic marker in the total cohort as well as in the group of 150 patients treated without nimorazole . Finally , no relation was found between the different expression levels of CA IX and the influence of nimorazole when locoregional control or disease-specific survival was used as endpoints . CONCLUSIONS This is to date one of the largest studies of CA IX in HNSCC . The data suggest that CA IX have no prognostic or predictive potential in patients with cancer in the head and neck treated with conventional radiotherapy and concomitant nimorazole Previously , we and others showed that hypoxia‐inducible factor‐1α ( HIF‐1α ) and transcriptionally upregulated Aurora‐A were required for disease progression in several tumors . Here , we address the clinicopathologic value of Aurora‐A and HIF‐1α in locally advanced nasopharyngeal carcinoma ( NPC ) . Aurora‐A and HIF‐1α expression was semiquantitatively evaluated by immunohistochemistry staining in 144 cases from a r and omized controlled trial . Of these patients , 69 received neoadjuvant chemotherapy plus concurrent chemoradiotherapy , and acted as the training set , and 75 cases treated with neoadjuvant chemotherapy plus radiotherapy were used as the testing set to vali date the prognostic effect of Aurora‐A and HIF‐1α . We found that Aurora‐A and HIF‐1α were highly expressed in NPC , but were deficient in normal adjacent epithelia . In the testing set , Aurora‐A overexpression predicted a shortened 5‐year overall survival ( 59.1 % vs 82.5 % , P = 0.024 ) , progression‐free survival ( 44.8 % vs 79.8 % , P = 0.004 ) , and distant metastasis‐free survival ( 43.0 % vs 17.3 % , P = 0.016 ) . Multivariate regression analysis confirmed that Aurora‐A was indeed an independent prognostic factor for death , recurrence , and distant metastasis both in the testing set and overall patients . Moreover , a positive correlation between Aurora‐A and HIF‐1α was detected ( P = 0.037 ) . Importantly , although HIF‐1α did not show any prognostic effect for patient outcome , the subset with Aurora‐A and HIF‐1α co‐overexpression had the poorest overall , progression‐free , and distant metastasis‐free survival ( all P < 0.05 ) . Our results confirmed that Aurora‐A was an independent prognostic factor for NPC . Aurora‐A combined with HIF‐1α refined the risk definition of the patient subset , thus potentially directing locally advanced NPC patients for more selective therapy . ( Cancer Sci , doi : 10.1111/j.1349‐7006.2012.02332.x , 2012 BACKGROUND AND PURPOSE In a phase III trial in patients with advanced stage laryngeal carcinoma comparing ARCON ( accelerated radiotherapy with carbogen breathing and nicotinamide ) to accelerated radiotherapy alone ( AR ) the prognostic and predictive value of CAIX , a hypoxia-associated protein , was investigated . MATERIAL AND METHODS 261 Paraffin embedded tumor biopsies and 79 fresh frozen biopsies from patients entered in the trial were immunohistochemically stained for CAIX . CAIX-fraction and CAIX expression pattern were related to tumor control and patient survival . RESULTS Low CAIX-fraction was prognostic for worse regional control and overall survival in patients treated with AR . Patients with a low CAIX-fraction treated with ARCON had better regional control and metastasis-free survival compared to AR ( RC 97 % vs 71 % , p < 0.01 and MFS 92 % vs 69 % , p = 0.06 ) . Patients with a perinecrotic CAIX staining pattern had a significantly worse local control , metastasis-free and overall survival compared to patients with a diffuse pattern ( 65 % vs 84 % , p = 0.01 , 70 % vs 96 % , p < 0.01 and 42 % vs 71 % , p < 0.01 respectively ) , and this could not be improved with ARCON . After multivariate analysis CAIX pattern and N-stage emerged as significant predictors for metastasis-free survival and overall survival . CONCLUSIONS ARCON improves regional control and metastasis-free survival only in patients with low CAIX expression . The different patterns of CAIX expression suggest different mechanisms of upregulation and have important prognostic value Abstract Purpose / Objective . A phase II clinical trial evaluating the feasibility and outcome of treating locally advanced head and neck squamous cell carcinoma ( HNSCC ) with accelerated radiotherapy , the hypoxic modifier nimorazole and weekly cisplatin . Material and methods . A total of 227 patients with stage III or IV HNSCC of the larynx , oropharynx , hypopharynx , or oral cavity where included between January 2007 and December 2010 . The prescribed radiotherapy ( RT ) dose was 66–68 Gy in 2 Gy fractions , 6 F/W. The hypoxic radiosensitiser nimorazole was given orally at a dose of 1200 mg/m2 before each fraction . Concomitant cisplatin ( 40 mg/m2 ) i.v . was given once a week for a maximum of six cycles . Outcome data were evaluated in terms of loco-regional tumour control ( LRC ) , event-free survival ( EFS ) and overall survival ( OS ) . Morbidity data were evaluated based on the DAHANCA routine registration . Human papillomavirus (HPV)-status was estimated by immunohistochemical staining of p16 . Results . Included were 178 ( 78 % ) men and 49 ( 22 % ) women with a median age of 57 years . All except five patients received RT as prescribed . At least five series of cisplatin was given to 164 ( 72 % ) of the patients , and 149 patients ( 66 % ) received the full dose of nimorazole . The five-year actuarial LRC , EFS and OS rates were 80 % , 67 % and 72 % , respectively . The LRC rates according to site were : oropharynx : 88 % , larynx : 77 % , hypopharynx 72 % and oral cavity 49 % , respectively . HPV/p16 staining was obtained in 141 of the 150 oropharyngeal cancers . Of these , 112 ( 79 % ) were p16 pos and 29 ( 21 % ) were p16 neg . LRC for the p16 neg oropharyngeal cancers was poorer than for the p16 pos ( 74 % vs. 91 % ; p = 0.02 ) . Tube feeding during treatment was necessary for 146 ( 64 % ) patients . At 12 months this number was reduced to 6 % . Conclusion . The treatment was tolerable in this cohort of locally advanced HNSCC patients . Acute and late toxicity was comparable to similar studies of chemoradiotherapy , and the outcome superior to the data reported in the literature . This strongly indicates that RT of advanced head and neck cancer must include as well hypoxic modification , accelerated fractionation as chemoradiotherapy to yield optimal outcome Purpose : Anemia is associated with poor tumor control . It was previously observed that accelerated radiotherapy combined with carbogen breathing and nicotinamide ( ARCON ) can correct this adverse outcome in patients with head and neck cancer . The purpose of this study was to vali date this observation based on data from a r and omized trial . Experimental Design : Of 345 patients with cT2 - 4 laryngeal cancer , 174 were r and omly assigned to accelerated radiotherapy and 171 to ARCON . Hemoglobin levels , measured before treatment , were defined as low when < 7.5 mmol/L for women and < 8.5 mmol/L for men . The hypoxia marker pimonidazole was used to assess the oxygenation status in tumor biopsies . Data were analyzed 2 years after inclusion of the last patient . Results : Pretreatment hemoglobin levels were available and below normal in 27 of 173 ( 16 % ) accelerated radiotherapy and 27 of 167 ( 16 % ) ARCON patients . In patients with normal pretreatment , hemoglobin levels treatment with ARCON had no significant effect on 5-year loco-regional control ( LRC , 79 % versus 75 % ; P = 0.44 ) and disease-free survival ( DFS , 75 % vs. 70 % ; P = 0.46 ) compared with accelerated radiotherapy . However , in patients with low pretreatment , hemoglobin levels ARCON significantly improved 5-year LRC ( 79 % vs. 53 % ; P = 0.03 ) and DFS ( 68 % vs. 45 % ; P = 0.04 ) . In multivariate analysis including other prognostic factors , pretreatment hemoglobin remained prognostic for LRC and DFS in the accelerated radiotherapy treatment arm . No correlation between pretreatment hemoglobin levels and pimonidazole uptake was observed . Conclusion : Results from the r and omized phase III trial support previous observations that ARCON has the potential to correct the poor outcome of cancer patients with anemia ( Clinical Trials.gov number , NCT00147732 ) . Clin Cancer Res ; 20(5 ) ; 1345–54 . © 2014 AACR PURPOSE Hypoxia adversely relates with prognosis in human tumours . Five hypoxia specific predictive marker assays were compared and correlated with definitive radiotherapy . PATIENTS AND METHODS Sixty-seven patients with advanced head and neck carcinomas were studied for pre-treatment plasma osteopontin measured by ELISA , tumour oxygenation status using pO(2 ) needle electrodes and tumour osteopontin , hypoxia inducible factor 1alpha ( HIF-1alpha ) and carboxyanhydrase 9 ( CA9 ) by immunohistochemistry . The primary treatment was radiotherapy and the hypoxic radiosensitizer nimorazole . Loco-regional tumour control was evaluated at 5 years . RESULTS All five markers showed inter-tumour variability . Inter-marker correlations were inconsistent . Only plasma osteopontin inversely correlated with median tumour pO(2 ) , ( p=0.02 , r=0.28 ) and CA9 correlated with HIF-1alpha ( p<0.01 , r=0.45 ) . In Kaplan-Meier analysis high plasma osteopontin , high HIF-1alpha and high proportion of tumour pO(2)2.5mmHg ( HP(2.5 ) ) related significantly with poorer loco-regional control , whereas CA9 and tumour osteopontin failed to predict loco-regional control in this set data set . When analyzing Hb , stage , and the five markers by competing risks HP(2.5 ) was the strongest variable to predict for loco-regional tumour control . CONCLUSION There was diversity and lack of correlation among five different hypoxia assays within individual tumours . High plasma osteopontin , high HIF-1alpha and high proportion of tumour pO(2)2.5mmHg ( HP(2.5 ) ) related significantly with poorer loco-regional control , whereas CA9 and tumour OPN failed to predict local control Purpose : Tumor hypoxia is associated with a poor prognosis , hypoxia modification improves outcome , and hypoxic status predicts benefit from treatment . Yet , there is no universal measure of clinical hypoxia . The aim of this study was to investigate whether a 26-gene hypoxia signature predicted benefit from hypoxia-modifying treatment in both cancer types . Experimental Design : Sample s were available from 157 T2–T4 laryngeal cancer and 185 T1–T4a bladder cancer patients enrolled on the accelerated radiotherapy with carbogen and nicotinamide ( ARCON ) and bladder carbogen nicotinamide ( BCON ) phase III r and omized trials of radiotherapy alone or with carbogen and nicotinamide ( CON ) respectively . Customized TaqMan low density arrays ( TLDA ) were used to assess expression of the 26-gene signature using quantitative real-time PCR . The median expression of the 26 genes was used to derive a hypoxia score ( HS ) . Patients were categorized as TLDA-HS low ( ≤median ) or TLDA-HS high ( > median ) . The primary outcome measures were regional control ( RC ; ARCON ) and overall survival ( BCON ) . Results : Laryngeal tumors categorized as TLDA-HS high showed greater benefit from ARCON than TLDA-HS low tumors . Five-year RC was 81 % ( radiotherapy alone ) versus 100 % ( CON ) for TLDA-HS high ( P = 0.009 ) . For TLDA-HS low , 5-year RC was 91 % ( radiotherapy alone ) versus 90 % ( CON ; P = 0.90 ) . TLDA-HS did not predict benefit from CON in bladder cancer . Conclusion : The 26-gene hypoxia signature predicts benefit from hypoxia-modifying treatment in laryngeal cancer . These findings will be evaluated in a prospect i ve clinical trial . Clin Cancer Res ; 19(17 ) ; 4879–88 . © 2013 AACR |
12,973 | 25,948,059 | Conclusions Based on this systematic review , CB DOT has a higher treatment success compared to clinic DOT . | Background Directly observed therapy ( DOT ) , as recommended by the World Health Organization , is used in many countries to deliver tuberculosis ( TB ) treatment .
The effectiveness of community-based ( CB DOT ) versus clinic DOT has not been adequately assessed to date .
We compared TB treatment outcomes of CB DOT ( delivered by community health workers or community volunteers ) , with those achieved through conventional clinic DOT . | Background One of the main strategies to control tuberculosis ( TB ) is to find and treat people with active disease . Unfortunately , the case detection rates remain low in many countries . Thus , we need interventions to find and treat sufficient number of patients to control TB . We investigated whether involving health extension workers ( HEWs : trained community health workers ) in TB control improved smear-positive case detection and treatment success rates in southern Ethiopia . Methodology /Principal Finding We carried out a community-r and omized trial in southern Ethiopia from September 2006 to April 2008 . Fifty-one kebeles ( with a total population of 296 , 811 ) were r and omly allocated to intervention and control groups . We trained HEWs in the intervention kebeles on how to identify suspects , collect sputum , and provide directly observed treatment . The HEWs in the intervention kebeles advised people with productive cough of 2 weeks or more duration to attend the health posts . Two hundred and thirty smear-positive patients were identified from the intervention and 88 patients from the control kebeles . The mean case detection rate was higher in the intervention than in the control kebeles ( 122.2 % vs 69.4 % , p<0.001 ) . In addition , more females patients were identified in the intervention kebeles ( 149.0 vs 91.6 , p<0.001 ) . The mean treatment success rate was higher in the intervention than in the control kebeles ( 89.3 % vs 83.1 % , p = 0.012 ) and more for females patients ( 89.8 % vs 81.3 % , p = 0.05 ) . Conclusions / Significance The involvement of HEWs in sputum collection and treatment improved smear-positive case detection and treatment success rate , possibly because of an improved service access . This could be applied in setting s with low health service coverage and a shortage of health workers . Trial Registration Clinical Trials.gov A r and omized controlled trial was carried out in Pakistan in 1999 to establish the effectiveness of the direct observation component of DOTS programmes . It found no significant differences in cure rates for patients directly observed by health facility workers , community health workers or by family members , as compared with the control group who had self-administered treatment . This paper reports on the social studies which were carried out during and after this trial , to explain these results . They consisted of a survey of all patients ( 64 % response rate ) ; in-depth interviews with a smaller sample of different types of patients ; and focus group discussion s with patients and providers . One finding was that of the 32 in-depth interview patients , 13 ( mainly from the health facility observation group ) failed to comply with their allocated DOT approach during the trial , citing the inconvenience of the method of observation . Another finding was that while patients found the overall TB care approach efficient and economical in general , they faced numerous barriers to regular attendance for the direct observation of drug-taking ( most especially , time , travel costs , ill health and need to pursue their occupation ) . This may be one of the reasons why there was no overall benefit from direct observation in the trial . Provider attitudes were also poor : health facility workers expressed cynical and uncaring views ; community health workers were more positive , but still arranged direct observation to suit their , rather than patients ' , schedules . The article concludes that direct observation , if used , should be flexible and convenient , whether at a health facility close to the patient 's home or in the community . The emphasis should shift in practice from tablet watching towards treatment support , together with education and other adherence measures We assessed the effect of community participation on treatment outcomes for tuberculosis patients undergoing directly-observed therapy , short course ( DOTS ) . From February to December 2001 172 newly diagnosed patients in Baghdad were allocated into 2 treatment groups . The intervention group were visited daily at home for the 2-month initial phase by trained members of the Iraqi Women 's Federation while the control group attended the local health centre for treatment . Cure rates for patients treated at home were significantly better than controls ( 83.7 % versus 68.6 % ) , so too was compliance ( 100.0 % versus 14.0 % ) . Smear conversion rates were significantly better in intervention cases compared with controls at all stages . Default rates were similar in both groups ( 11.6 % versus 10.5 % ) , as was mortality ( 1 patient each ) SETTING Two small urban townships ( compounds ) in Ndola , Zambia , served by an HIV/AIDS home care programme . OBJECTIVE To evaluate the implementation of the directly observed treatment , short-course ( DOTS ) strategy as part of an existing HIV/AIDS home care programme , by comparing TB treatment outcomes in an intervention population ( Chipulukusu compound ) , where implementation of the DOTS strategy is an integral part of the HIV/AIDS home care programme , and in a control population ( Twapia compound ) with district TB services but as yet without coverage by the HIV/AIDS home care programme . DESIGN Prospect i ve evaluation of all new sputum smear-positive TB patients registered in Chipulukusu and Twapia compounds between 1 February 1998 and 30 September 1999 , with documentation of 2-month sputum smear conversion and 8-month treatment outcomes . RESULTS There were 72 new sputum smear-positive pulmonary TB cases in Chipulukusu and 96 in Twapia registered during the study period . In comparing treatment outcomes in Chipulukusu and Twapia , there was no significant difference in treatment success ( cure plus treatment completion ) ( 61 % vs. 48.9 % ) or in deaths ( 22 % vs. 19 % ) . However , cure rate was significantly higher in Chipulukusu than in Twapia ( 54.2 % vs. 20.8 % ) and treatment interruption was significantly lower in Chipulukusu than in Twapia ( 8.3 % vs. 22.9 % ) . CONCLUSION Integration of the DOTS strategy for TB control with an existing HIV/AIDS home care programme led to improved TB programme performance in a compound with a small population ( about 20000 ) . There is scope to scale up this approach so that the entire population of all the compounds in Ndola served by the HIV/AIDS home care programme can benefit from improved TB control While directly observed treatment ( DOT ) has been recommended as the st and ard approach to tuberculosis control , empirical data on its feasibility and efficiency are still scarce . We conducted a controlled trial of DOT at 15 health care facilities at various levels of the government health care system in Thail and . A total of 836 patients diagnosed between August 1996 and October 1997 were r and omly assigned to be treated either under DOT or self-supervised using monthly drug supplies ( SS ) . Options for treatment supervisors were health staff , community members or members of the patients ' families . Treatment outcomes were compared on the basis of cure , treatment-completion , default and death rates . In both study arms , treatment outcomes were improved compared to pre- study conditions . Cure and treatment-completion rates were significantly higher in the DOT cohort ( 76 % and 84 % ) than in the SS group ( 67 % and 76 % ) . The benefits of DOT were more pronounced at district and provincial hospitals ( DOT cure rate 81 % vs. 69 % in the SS group ) , while differences for patients treated at referral centres were non-significant ( DOT cure rate 72 % vs. 66 % in the SS group ) . No significant differences in outcomes could be observed between patient groups receiving DOT under the various options for treatment supervisors . DOT appears especially suited for treatment at de central ized facilities . While a general focus on programme performance can improve outcomes , DOT provides significant additional benefits . If basic conditions are met , a DOT strategy can be tailored to country-specific conditions by exploring multiple observation options , without decreasing its effectiveness Background Directly observed therapy ( DOT ) remains the cornerstone of the global tuberculosis ( TB ) control strategy . Tanzania , one of the 22 high-burden countries regarding TB , changed the first-line treatment regimen to contain rifampicin-containing fixed-dose combination for the full 6 months of treatment . As daily health facility-based DOT for this long period is not feasible for the patient , nor for the health system , Tanzania introduced patient centred treatment ( PCT ) . PCT allows patients to choose for daily DOT at a health facility or at their home by a supporter of choice . The introduction of fixed dose combinations in the intensive and continuation phase made PCT feasible by eliminating the risk of selective drug taking by patients and reducing the number of tablets to be taken . The approach was tested in three districts with the objective to assess the effect of this strategy on TB treatment outcomes Methods Cohort analysis comparing patients treated under the PCT strategy ( registered April-September 2006 ) with patients treated under health-facility-based DOT ( registered April-September 2005 ) . The primary outcome was the cure rate . Differences were assessed by calculating the risk ratios . Associations between characteristics of the supporters and treatment outcomes in the group of patients opting for home-based DOT were assessed through logistic regression . Results In the PCT cohort there were 1208 patients and 1417 were included in the historic cohort . There was no significant difference in cure rates between the cohorts ( risk ratio [ RR ] : 1.06 ; 95 % confidence interval [ CI ] : 0.96 - 1.16 ) . In the PCT cohort , significantly more patients had successful treatment ( cure or treatment completed ; RR : 1.10 ; 95%CI : 1.01 - 1.15 ) . There were no characteristics of supporters that were associated with treatment outcome . Conclusion The PCT approach showed similar cure rates and better treatment success rates compared to daily health-facility DOT . The results indicate that there are no specific prerequisites for the supporter chosen by the patient . The programmatic setting of the study lends strong support for scaling-up of TB treatment observation outside the health facility by HEWs in the health posts and general health workers at health facility were compared along a community-r and omized trial . Costs were analysed from societal perspective in 2007 in US $ using st and ard methods . We prospect ively enrolled smear positive patients , and calculated cost-effectiveness as the cost per patient successfully treated . The total cost for each successfully treated smear-positive patient was higher in health facility ( $ 158.9 ) compared with community ( $ 61.7 ) . Community-based treatment reduced the total , patient and caregiver cost by 61.2 % , 68.1 % and 79.8 % , respectively . Involving HEWs added a total cost of $ 8.80 ( 14.3 % of total cost ) on health service per patient treated in the community . Conclusions / Significance Community-based treatment by HEWs costs only 39 % of what treatment by general health workers costs for similar outcomes . Involving HEWs in TB treatment is a cost effective treatment alternative to the health service , to the patients and the family . There is an economic and public health reason to consider involving HEWs in TB treatment in Ethiopia . However , community-based treatment requires initial investment to start its implementation , training and supervision . Trial Registration Clinical Trials.gov BACKGROUND Tuberculosis remains a major public-health problem in Bangladesh , despite national efforts to improve case identification and treatment compliance . In 1984 , BRAC ( formerly the Bangladesh Rural Advancement Committee ) , a national , non-governmental organisation , began an experimental tuberculosis-control programme in one thana ( subdistrict ) . Community health workers screened villagers for chronic cough and collected sputum sample s for acid-fast bacillus ( AFB ) microscopy ( phase one ) . Positive patients received 12 months of directly observed therapy . Phase two ( 1992 - 94 ) included another nine thanas and , in phase three ( 1995 ) , eight more thanas were included . From 1995 , the treatment was an 8-month oral regimen . METHODS In 1995 - 96 , we analysed all programme data from 1992 to 1995 . First we analysed phases two ( 12-month therapy ) and three ( 8-month therapy ) separately for proportion cured , died , treatment , failed , defaulted , migrated , and referred . Second , we did a cross-sectional survey of tuberculosis cases in more than 9000 r and omly selected households in two phase-two thanas and one non-programme thana , and analysed the follow-up of all patients treated in the programme thanas . FINDINGS In the phase-two analysis , 3497 ( 90 % ) of 3886 cases identified had accepted 12-month treatment . In phase three , all of 1741 identified cases accepted the 8-month regimen . 2833 ( 81.0 % ) and 1496 ( 85.9 % ) in phases two and three , respectively , were cured ; 336 ( 9.6 % ) and 133 ( 7.6 % ) died . The relapse rate 2 or more years after treatment was discontinued was higher than the early relapse rate . The drop-out rate was 3.1 % . In the cross-sectional survey , the prevalence of tuberculosis in the two programme thanas was half of that in the comparison thana , where only government services were available ( 0.07 vs 0.15 per 100 [ corrected ] ) . INTERPRETATION The BRAC tuberculosis-control programme has successfully achieved high rates of case detection and treatment compliance , with a cure rate of at least 85 % and a drop-out rate of 3.1 % . The prevalence survey suggested that at least half of all existing cases had been detected by the programme SETTING An urban district in Dar es Salaam city with a high tuberculosis ( TB ) caseload . OBJECTIVE To evaluate the effectiveness of community-based direct observation of treatment ( DOT ) using guardians and former TB patients compared to hospital-based DOT in an urban setting in Tanzania . DESIGN Unblinded r and omised control trial conducted in five sites under operational conditions in Temeke district . No changes to existing treatment delivery were made other than r and omisation . The main outcome measure was treatment success . Analysis was by intention to treat . FINDINGS A total of 587 new tuberculosis patients were enrolled . Among enrolled patients , 260 were assigned to community-based DOT using guardians and former TB patients and 327 to health facility-based DOT . Both DOT options gave similar treatment outcomes . Treatment success rate among patients under community and health facility-based DOT were 85 % and 83 % , respectively ( OR 1.17 , 95%CI 0.75 - 1.83 ) . CONCLUSION Community-based DOT is as effective as health facility-based DOT and can achieve good treatment outcomes , even in countries with well functioning National Tuberculosis Programmes An economic study was conducted alongside a clinical trial at three sites in Pakistan to establish the costs and effectiveness of different strategies for implementing directly observed treatment ( DOT ) for tuberculosis . Patients were r and omly allocated to one of three arms : DOTS with direct observation by health workers ( at health centres or by community health workers ) ; DOTS with direct observation by family members ; and DOTS without direct observation . The clinical trial found no statistically significant difference in cure rate for the different arms . The economic study collected data on the full range of health service costs and patient costs of the different treatment arms . Data were also disaggregated by gender , rural and urban patients , by treatment site and by economic categories , to investigate the costs of the different strategies , their cost-effectiveness and the impact that they might have on patient compliance with treatment . The study found that direct observation by health centre-based health workers was the least cost-effective of the strategies tested ( US dollars 310 per case cured ) . This is an interesting result , as this is the model recommended by the World Health Organization and International Union against Tuberculosis and Lung Disease . Attending health centres daily during the first 2 months generated high patient costs ( direct and in terms of time lost ) , yet cure rates for this group fell below those of the non-observed group ( 58 % , compared with 62 % ) . One factor suggested by this study is that the high costs of attending may be deterring patients , and in particular , economically active patients who have most to lose from the time taken by direct observation . Without stronger evidence of benefits , it is hard to justify the costs to health services and patients that this type of direct observation imposes . The self-administered group came out as most cost-effective ( 164 dollars per case cured ) . The community health worker sub-group achieved the highest cure rates ( 67 % ) , with a cost per case only slightly higher than the self-administered group ( 172 dollars per case cured ) . This approach should be investigated further , along with other approaches to improving patient compliance SETTING Low income , high density , urban settlements in Cape Town , South Africa . OBJECTIVES To evaluate community treatment supervision as part of tuberculosis ( TB ) programme implementation . DESIGN A non-r and omised prospect i ve study was conducted under programme conditions from January 1998 to December 1999 , comparing TB programme performance in an area with ( Guguletu ) , and an area without ( Nyanga ) the option of TB treatment supervision by community health workers . RESULTS Data were collected for 2873 adult TB patients . For smear-positive TB patients , treatment cure rates were higher in the intervention area ( Guguletu ) than in the control area ( Nyanga ) ( 58 % vs. 50 % , P = 0.0378 ) and for retreatment cases ( 47 % vs. 35 % , P = 0.0791 ) , treatment success rates were similar . CONCLUSIONS Community health worker support contributed to better TB control programme performance than an approach based exclusively on health facilities . Clear government policy and support for lay health worker programmes in TB control is needed BACKGROUND Tuberculosis is a major public-health problem in South Africa , made worse by poor adherence to and frequent interruption of treatment . Direct observation ( DO ) of tuberculosis patients taking their drugs is supposed to improve treatment completion and outcome . We compared DO with self-supervision , in which patients on the same drug regimen are not observed taking their pills , to assess the effect of each on the success of tuberculosis treatment . METHODS We undertook an unblinded r and omised controlled trial in two communities with large tuberculosis caseloads . The trial included 216 adults who started pulmonary tuberculosis treatment for the first time , or who had a second course of treatment ( retreatment patients ) . No changes to existing treatment delivery were made other than r and omisation . Analysis was by intention to treat . Individual patient data from the two communities were combined . FINDINGS Treatment for tuberculosis was more successful among self-supervised patients ( 60 % of patients ) than among those on DO ( 54 % of patients , difference between groups 6 % [ 90 % CI -5.1 to 17.0 ] ) . Retreatment patients had significantly more successful treatment outcomes if self-supervised ( 74 % of patients ) than on DO ( 42 % of patients , difference between groups 32 % [ 11%-52 % ] ) . INTERPRETATION At high rates of treatment interruption , self-supervision achieved equivalent outcomes to clinic DO at lower cost . Self-supervision achieved better outcomes for retreatment patients . Supportive patient-carer relations , rather than the authoritarian surveillance implicit in DO , may improve treatment outcomes and help to control tuberculosis Tuberculosis ( TB ) has reappeared as a serious public health problem . Non-compliance to antituber-culous drug treatment is cited as one of the major obstacles to the containment of the epidemic . Compliance may be optimized by Directly Observed Treatment ( DOT ) and short-course treatment regimens . Since 1986 , Tanzanian TB patients have received daily DOT at health facilities for the first 2 months of the treatment course . However , adherence and cure rates have been falling as the number of TB cases continues to increase and the burden on already stretched health facilities threatens to become unmanageable . We used an open cluster r and omized controlled trial to compare community-based DOT ( CBDOT ) using a short-course drug regimen with institutional-based DOT ( IBDOT ) . A total of 522 ( 301 IBDOT and 221 CBDOT ) patients with sputum-positive TB were recruited . Overall , there was no significant difference in conversion and cure rates between the two strategies [ M-H pooled odds ratio ( OR ) 0.62 ; 95 % confidence interval ( CI ) 0.23 , 1.71 and OR = 1.58 ; 95 % CI 0.32 , 7.88 , respectively ] suggesting that CBDOT may be a viable alternative to IBDOT . CBDOT may be particularly useful in parts of the country where people live far from health facilities BACKGROUND Tuberculosis ( TB ) remains a widespread healthcare problem in Africa , although it can be cured within 6 - 8 months ' effective treatment . However , many patients fail to adhere to TB treatment , result ing in failure to get cured and the possible development of multi-drug resistant TB ( MDR TB ) . A community-based TB treatment programme , was started in the Omaheke region of Namibia during 2002 . The efficacy of this community-based TB programme , compared to the st and ard hospital- and clinic-based TB treatment , was unknown . OBJECTIVES The major objectives were to compare TB treatment outcomes for patients who used the community-based TB with those who chose the clinic/self-administered TB treatment option ; and to identify advantages and disadvantages of community-based TB care as experienced by patients who had completed their community-based TB treatment . DESIGN A quasi-experimental study design was used to compare TB patients ' treatment outcomes using checklists and exit interviews . SETTING The study was conducted in the Omaheke region of Namibia . PARTICIPANTS TB patients ( n=332 ) who were hospitalised during the study period participated in the study . METHODS An analytic cohort prospect i ve design was used to do follow-up visits , and complete checklists , of 332 TB patients . Structured exit interviews were conducted with 101 TB patients who had completed their community-based TB treatment . RESULTS Enhanced knowledge of TB patients improved their participation in community-based TB care . A family member was the most convenient , acceptable and accessible directly observed treatment ( DOT ) supervisor for 72.8 % of the participants . A statistically significant difference in cure rates between community-based and the clinic/self-administered groups was found ( chi(2 ) 11.78 ; p < or=0.05 ; and RR=1.35 ; p=0.05 ) . The major advantages of community-based TB treatment included the ability to continue with one 's daily activities during treatment and the saving of time and money . The major disadvantages included that the clinics ran out of TB drug supplies , patients did not always have food to eat after taking their pills and they could not get sufficient rest because they had to continue doing their daily chores . CONCLUSIONS TB patients on the community-based TB treatment option had better cure rates than those on clinic/self-administered TB treatment ( although it can not be inferred that the community-based treatment caused the improved cure rates , because the TB patients who did not select the community-based treatment option might have been different ) . The advantages experienced by patients who completed their community-based TB treatment outweighed the disadvantages BACKGROUND DOTS is the control strategy for tuberculosis promoted by WHO . Pakistan is currently developing its National Tuberculosis Programme , and requires guidance on types of direct observation of treatment appropriate for the local conditions . We did a r and omised trial to assess the effectiveness of different packages for tuberculosis treatment under operational conditions in Pakistan . METHODS We enrolled 497 adults with new sputum-positive tuberculosis . 170 were assigned DOTS with direct observation of treatment by health workers ; 165 were assigned DOTS with direct observation of treatment by family members ; and 162 were assigned self-administered treatment . The trial was done at three sites that provide tuberculosis services strengthened according to WHO guidelines for the purpose s of the research , with a st and ard daily short-course drugs regimen ( 2 months of isoniazid , rifampicin , pyrazinamide , and ethambutol , followed by 6 months of isoniazid and ethambutol ) . The main outcome measures were cure , and cure or treatment completion . Analysis was by intention to treat . FINDINGS Within the strengthened tuberculosis services , the health-worker DOTS , family-member DOTS , and self-administered treatment strategies gave very similar outcomes , with cure rates of 64 % , 55 % , and 62 % , respectively , and cure or treatment-completed rates of 67 % , 62 % , and 65 % , respectively . INTERPRETATION None of the three strategies tested was shown to be superior to the others , and direct observation of treatment did not give any additional improvement in cure rates . The effectiveness of direct observation of treatment remains unclear , and further operational research is needed OBJECTIVE To vali date the practice of directly observed treatment ( DOT ) and evaluate its effect on treatment outcomes . METHODS This follow-up study conducted in 24 districts in southern Thail and included 411 new , smear-positive , pulmonary tuberculosis ( TB ) patients who started treatment between February and September 1999 . Patients and /or their observers were interviewed about their actual DOT practice during the first 2 months of treatment . Treatment outcomes were evaluated at the end of the second month and at the end of treatment . RESULTS Of 411 patients , 379 were assigned to DOT but only 68 practised strict DOT for every dose during the first 2 months . Adjusted odds ratios ( ORs ) for ' no sputum conversion ' and ' unsuccessful treatment ' were 1.1 ( 95 % CI 0.6 - 2.1 ) and 1.3 ( 95 % CI 0.6 - 2.8 ) , respectively , for those who practised strict DOT vs. the rest . CONCLUSIONS Actual practice of DOT was quite different from what was intended at the assignment . Practice of strict DOT during the first 2 months was not associated with sputum conversion or treatment success in this study area A prospect i ve study was conducted in 24 districts in southern Thail and in 1999 with directly observed treatment , short-course strategy ( DOTS ) implemented to determine treatment outcomes in relation to the practical observer among 455 enrolled patients with tuberculosis . Health personnel ( HP ) , community members ( CM ) , family members ( FM ) and self-administration ( SA ) were initially assigned to be DOT observers in 43 % , 5 % , 44 % and 8 % of 411 analysed patients , respectively . In practice , 56 % of the 379 patients with assigned observers changed their observers . The practical observer was the assigned observer among 17 % of patients assigned to HP , 57 % to CM , 75 % to FM , and 34 % to SA , respectively . There were no significant differences in treatment success between different types of main observers . Adjusted odds ratios ( 95 % confidence interval ) of treatment non-success were 1.1 ( 0.3 - 4.7 ) , 0.7 ( 0.2 - 3.3 ) , and 0.5 ( 0.2 - 1.1 ) for HP , CM , and FM , over SA groups , respectively . HP may not be the best choice in our setting due to poor sustainability and the availability of another promising choice ( CM ) SETTING The Northern Cape Province , Republic of South Africa . OBJECTIVES To determine the effect of patient choice of treatment delivery option on the treatment outcomes of tuberculosis ( TB ) patients in a high burden setting under actual programme conditions . DESIGN Cohort study involving 769 new and retreatment TB patients recruited from 45 r and omly selected clinics . Patients were interviewed and subsequent follow-up was done through regular visits to the clinics to check progress through formal health records . RESULTS There was a statistically significant difference ( P < 0.001 ) between the treatment outcome of new patients ( 70 % successful ) and re-treatment patients ( 54 % successful ) . Direct observation of treatment ( DOT ) was found to have no effect on the treatment outcome of new patients ( P = 0.875 ) , but re-treatment patients were found to fare better with than without DOT ( OR 14.2 , 95 % CI 4.18 - 53.14 , P < 0.001 ) . CONCLUSION The results obtained for new patients are similar to those of two recent r and omised controlled trials on DOT . This study revealed that for new patients , undue emphasis on universal DOT might be unnecessary . It would perhaps be more beneficial to target supervision at those patients who are most likely to benefit from it ( i.e. , re-treatment patients ) . This is of particular relevance in high burden , re source -limited setting s where universal DOT for all TB patients is generally unfeasible We implemented community-based direct observation of treatment , short course ( DOTS ) , including a r and omized controlled trial of direct observation either by community health workers ( CHWs ) or family members , under operational conditions in a region of Swazil and . There was a high death rate of 15 % , due to the high HIV rates in the region . There was no significant difference in the cure and completion rate between direct observation of treatment by CHWs and family members [ 2 % difference ( 95 % CI -3 % to 7 % ) , exact P = 0.52 ] . A before- and -after comparison of outcomes demonstrated that the cure and treatment completion rate improved from a baseline of 27 - 67 % following implementation of community-based DOTS . We conclude that community-based tuberculosis DOTS can improve successful outcomes of treatment . However , direct observation can be undertaken effectively using either daily family or CHW supervision . The choice of treatment supporter should be based on access , patient preference and availability of CHW re source Directly observed therapy short course ( DOTS ) is an effective strategy for controlling tuberculosis ( TB ) , and is used worldwide , mainly in developing countries . The success of this treatment for out patients with TB was reported in Bangladesh , China , Malawi , and other countries . The method was used by families and village health workers in the communities . A r and omized-controlled trial in Pakistan showed no substantial difference in the effectiveness between DOTS by health workers and family members . In Cambodia , DOTS started in 1999 in health centres for outpatient treatment ( HC-DOTS ) . This programme could not be provided for patients in rural areas . However , in 2002 , DOTS in the communities ( C-DOTS ) was implemented . In this paper , we compare the results of TB treatment between HC-DOTS and C-DOTS in Cambodia BACKGROUND A key component of the DOTS strategy for tuberculosis control ( short-course chemotherapy following WHO guidelines ) is direct observation of treatment . WHO technical guidelines recommend that health workers should undertake this part of the strategy , but will also accept direct observation of treatment in the community ; WHO does not think that a family member should undertake this role . Supporting evidence for these recommendations is not available . The Nepal national tuberculosis programme asked us to develop and test a strategy of direct observation of treatment for the hill districts of Nepal , where direct observation of treatment by health workers is not feasible . We aim ed to assess the success rates of two DOTS strategies developed for such areas . METHODS Between mid-July , 2002 , and mid-July , 2003 , we undertook a cluster-r and omised controlled trial to compare two strategies-community DOTS and family-member DOTS -- in ten hill and mountain districts of Nepal . Districts were used as the unit of r and omisation . Primary outcome was success rate ( proportion of registered patients who achieved cure or completed treatment ) , and analysis was by intention to treat . FINDINGS Five districts ( 549 patients ) were allocated to community DOTS and five ( 358 patients ) were allocated family-member DOTS . Community DOTS and family-member DOTS achieved success rates of 85 % and 89 % , respectively ( odds ratio of success for community DOTS relative to family-member DOTS , 0.67 [ 95 % CI 0.41 - 1.10 ] ; p=0.09 ) . Estimated case-finding rates were 63 % with the community strategy and 44 % with family-member DOTS . INTERPRETATION The family-member DOTS and community DOTS strategies can both attain international targets for treatment success under programme conditions , and thus are appropriate for the hill and mountain districts of Nepal . Both strategies might also be appropriate in other parts of the world where directly observed treatment by health workers is not feasible . Our findings lend support to adoption of this patient-responsive approach to direct observation of treatment within global tuberculosis control policy SETTING Study conducted in a suburb of Cape Town , South Africa . OBJECTIVE Comparison of successful tuberculosis treatment outcome rates between self supervision , supervision by lay health worker ( LHW ) , and supervision by clinic nurse . METHODS Open , r and omised , controlled trial with intention-to-treat analysis . RESULTS All groups ( n = 156 ) achieved similar outcomes ( LHW vs. clinic nurse : risk difference 17.2 % , 95 % confidence interval [ CI ] -0.1 - 34.5 ; LHW vs. self supervision 15 % , 95%CI -3.7 - 33.6 ) . New patients benefit from LHW supervision ( LHW vs clinic nurse : risk difference 24.2 % , 95%CI 6 - 42.5 , LHW vs. self supervision 39.1 % , 95%CI 17.8 - 60.3 ) as do female patients ( LHW vs. clinic nurse 48.3 % , 95%CI 22.8 - 73.8 , LHW vs. self supervision 32.6 % , 95%CI 6.4 - 58.7 ) . CONCLUSIONS LHW supervision approaches statistically significant superiority , but fails to reach it most likely due to the study 's limitation , the small sample size . It is possible that subgroups ( new and female patients ) do well under LHW supervision . LHW supervision could be offered as one of several supervision options within TB control programmes |
12,974 | 29,683,925 | Conclusions HIIT elicits improvements in objective measures of CRF within 8 wk in diseased cohorts compared with no intervention .
When compared with MCT , HIIT imparts statistically significant additional improvements in measures of CRF , with clinical ly important additional improvements in V˙O2peak in cardiovascular patients . | Background and Aim Exercise training regimes can lead to improvements in measures of cardiorespiratory fitness ( CRF ) , improved general health , and reduced morbidity and overall mortality risk .
High-intensity interval training ( HIIT ) offers a time-efficient approach to improve CRF in healthy individuals , but the relative benefits of HIIT compared with traditional training methods are unknown in across different disease cohorts . | Aims /hypothesisCardiac disease remains the leading cause of mortality in type 2 diabetes , yet few strategies to target cardiac dysfunction have been developed . This r and omised controlled trial aim ed to investigate high intensity intermittent training ( HIIT ) as a potential therapy to improve cardiac structure and function in type 2 diabetes . The impact of HIIT on liver fat and metabolic control was also investigated . Methods Using an online r and om allocation sequence , 28 patients with type 2 diabetes ( metformin and diet controlled ) were r and omised to 12 weeks of HIIT ( n = 14 ) or st and ard care ( n = 14 ) . Cardiac structure and function were measured by 3.0 T MRI and tagging . Liver fat was determined by 1H-magnetic resonance spectroscopy and glucose control by an OGTT . MRI analysis was performed by an observer blinded to group allocation . All study procedures took place in Newcastle upon Tyne , UK . Results Five patients did not complete the study and were therefore excluded from analysis : this left 12 HIIT and 11 control patients for the intention-to-treat analysis . Compared with controls , HIIT improved cardiac structure ( left ventricular wall mass 104 ± 17 g to 116 ± 20 g vs 107 ± 25 g to 105 ± 25 g , p < 0.05 ) and systolic function ( stroke volume 76 ± 16 ml to 87 ± 19 ml vs 79 ± 14 ml to 75 ± 15 ml , p < 0.01 ) . Early diastolic filling rates increased ( 241 ± 84 ml/s to 299 ± 89 ml/s vs 250 ± 44 ml/s to 251 ± 47 ml/s , p < 0.05 ) and peak torsion decreased ( 8.1 ± 1.8 ° to 6.9 ± 1.6 ° vs 7.1 ± 2.2 ° to 7.6 ± 1.9 ° , p < 0.05 ) in the treatment group . Following HIIT , there was a 39 % relative reduction in liver fat ( p < 0.05 ) and a reduction in HbA1c ( 7.1 ± 1.0 % [ 54.5 mmol/mol ] to 6.8 ± 0.9 % [ 51.3 mmol/mol ] vs 7.2 ± 0.5 % [ 54.9 mmol/mol ] to 7.4 ± 0.7 % [ 57.0 mmol/mol ] , p < 0.05 ) . Changes in liver fat correlated with changes in HbA1c ( r = 0.70 , p < 0.000 ) and 2 h glucose ( r = 0.57 , p < 0.004 ) . No adverse events were recorded . Conclusions /interpretationThis is the first study to demonstrate improvements in cardiac structure and function , along with the greatest reduction in liver fat , to be recorded following an exercise intervention in type 2 diabetes . HIIT should be considered by clinical care teams as a therapy to improve cardiometabolic risk in patients with type 2 diabetes . Trial registration : www.is rct n.com 78698481 Funding : Medical Research Council Limited information is available regarding the physiological responses to different types of exercise training in patients with severe chronic obstructive pulmonary disease ( COPD ) . The aim of this study was two fold : firstly , to investigate the physiological response to training at 60 % of achieved peak load in patients with severe COPD ; and secondly to study the effects of interval ( I ) versus continuous ( C ) training in these patients . Twenty-one patients with COPD ( mean+/-SD forced expiratory volume in one second : 37+/-15 % of predicted , normoxaemic at rest ) were evaluated at baseline and after 8 weeks ' training . Patients were r and omly allocated to either I or C training . The training was performed on a cycle ergometer , 5 days a week , 30 min daily . The total work load was the same for both training programmes . C training result ed in a significant increase in oxygen consumption ( V'O2 ) ( 17 % , p<0.05 ) and a decrease in minute ventilation (V'E)/V'O2 ( p<0.01 ) and V'E/carbon dioxide production ( V'CO2 ) ( p<0.05 ) at peak exercise capacity , while no changes in these measures were observed after interval training . During submaximal exercise a significant decrease was observed in lactic acid production , being most pronounced in the C-trained group ( -31 % , p<0.01 versus -20 % , p<0.05 ) . Only in the I-trained group did a significant increase in peak work load ( 17 % , p<0.05 ) and a decrease in leg pain ( p<0.05 ) occur . Training did not result in a significant improvement in lung function , but maximal inspiratory mouth pressure increased in both groups by 10 % ( C : p<0.05 ) and 23 % ( I : p<0.01 ) . The present study shows a different physiological response pattern to interval or continuous training in chronic obstruction pulmonary disease , which might be a reflection of specific training effects in either oxidative or glycolytic muscle metabolic pathways . Further work is required to determine the role of the different exercise programmes and the particular category of patients for whom this might be beneficial 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 Exercise can have anti-inflammatory effects in obesity , but the optimal type and intensity of exercise are not clear . This study compared short-term high-intensity interval training ( HIIT ) with moderate-intensity continuous training ( MICT ) in terms of improvement in cardiorespiratory fitness , markers of inflammation , and glucose control in previously inactive adults at elevated risk of developing type 2 diabetes . Thirty-nine inactive , overweight/obese adults ( 32 women ) were r and omly assigned to 10 sessions over 2 wk of progressive HIIT ( n = 20 , four to ten 1-min sessions at ∼90 % peak heart rate , 1-min rest periods ) or MICT ( n = 19 , 20 - 50 min at ∼65 % peak heart rate ) . Before and 3 days after training , participants performed a peak O2 uptake test , and fasting blood sample s were obtained . Both HIIT ( 1.8 ± 0.4 vs. 1.9 ± 0.4 l/min , pre vs. post ) and MICT ( 1.8 ± 0.5 vs. 1.9 ± 0.5 l/min , pre vs. post ) improved peak O2 uptake ( P < 0.001 ) and lowered plasma fructosamine ( P < 0.05 ) . Toll-like receptor ( TLR ) 4 ( TLR4 ) expression was reduced on lymphocytes and monocytes after both HIIT and MICT ( P < 0.05 ) and on neutrophils after MICT ( P < 0.01 ) . TLR2 on lymphocytes was reduced after HIIT and MICT ( P < 0.05 ) . Plasma inflammatory cytokines were unchanged after training in both groups , but MICT led to a reduction in fasting plasma glucose ( P < 0.05 , 5.9 ± 1.0 vs. 5.6 ± 1.0 mmol/l , pre vs. post ) . Ten days of either HIIT or MICT can improve cardiorespiratory fitness and glucose control and lead to reductions in TLR2 and TLR4 expression . MICT , which involved a longer duration of exercise , may be superior for reducing fasting glucose 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 Increasing evidence suggests that high-intensity training ( HIT ) is a time-efficient exercise strategy to improve fitness . HIT has never been explored in neuromuscular diseases , likely because it may seem counterintuitive . A single session of high-intensity exercise has been studied without signs of muscle damage in facioscapulohumeral muscular dystrophy type 1 ( FSHD1 ) . We aim ed to determine whether HIT is safe and effective in FSHD1 in a r and omized , controlled parallel study . Untrained adults with genetically verified FSHD1 ( n = 13 ) able to perform cycle-ergometer exercise were r and omized to 8 weeks of supervised HIT ( n = 6 ) ( 3 × 10-min cycle-ergometer-HIT/week ) or 8 weeks of usual care ( n = 7 ) . Following this , all participants performed 8 weeks of unsupervised HIT ( 3 × 10-min cycle-ergometer-HIT/week ) . Primary outcome was fitness , maximal oxygen uptake/min/kg body weight . Furthermore , workload , 6-min walk distance , 5-time sit-to-st and time , muscle strength , and daily activity levels were measured . Pain , fatigue , and plasma-CK were monitored . Twelve patients completed the r and omized part of the study . Plasma-CK levels and pain scores were unaffected by HIT . Supervised HIT improved fitness ( 3.3 ml O2/min/kg , CI 1.2–5.5 , P < 0.01 , n = 6 , NNT = 1.4 ) . Unsupervised HIT also improved fitness ( 2.0 ml O2/min/kg , CI 0.1–3.9 , P = 0.04 , n = 4 ) . There was no training effect on other outcomes . Patients preferred HIT over strength and moderate-intensity aerobic training . It may seem counterintuitive to perform HIT in muscular dystrophies , but this RCT shows that regular HIT is safe , efficacious , and well liked by moderately affected patients with FSHD1 , which suggests that HIT is a feasible method for rehabilitating patients with FSHD1 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 BACKGROUND Colorectal cancer is the third most common cancer in the UK , with patients suffering declines in muscle mass and aerobic function . We hypothesised that tumour removal in non-metastatic colorectal cancer would lead to a restoration of lean muscle mass and increases in objective and subjective measures of aerobic performance . METHODS We recruited two groups : patients with colorectal cancer ( n = 30 , 65.3 ( 51 - 77 ) y , body mass index 27.67 ( 4.83 ) kg m(-2 ) ) and matched controls ( n = 30 , 64.6 ( 42 - 77 ) y , BMI 27.14 ( 3.51 ) kg m(-2 ) ) . Controls underwent a single study while colorectal cancer patients were studied before and 10 months after tumour resection . Aerobic performance was assessed via cardiopulmonary exercise testing and activity question naires . Lean muscle mass was measured via dual-energy X-ray absorptiometry . RESULTS Lean muscle mass was not different between groups ( control : 47.82 ( 8.23 ) ; pre-resection : 52.41 ( 10.59 ) ; post-resection : 52.38 ( 10.52 ) , kg ) . Anaerobic threshold was lower in pre-operative patients compared to controls ( 14.40 ( 3.23 ) vs. 19.67 ( 5.81 ) ml kg(-1 ) min(-1 ) , p < 0.0001 ) , increasing significantly post-resection ( 17.00 ( 3.56 ) ml kg(-1 ) min(-1)p < 0.0001 ) . Self reported maximal physical activity was lower after resection compared to preoperatively ( pre-resection 6.0 ( 6.5 - 5 IQR ) , post-resection 3.75 ( 4 - 3 IQR ) , p < 0.0001 ) . CONCLUSION In colorectal cancer , anaerobic threshold is reached more rapidly than in matched controls , returning toward normal with tumour resection . Self-reported measures of activity do not mirror this objective change , cardiopulmonary exercise testing may therefore allow for a more accurate evaluation of pre and postoperative performance capability . The variance between objective and subjective measures of exercise capacity may be important in determining return to normal activities Background : Patients with schizophrenia have a high risk of cardiovascular disease ( CVD ) . High aerobic intensity training ( HIT ) improve peak oxygen uptake ( VO2peak ) , net mechanical efficiency of walking and risk factors for CVD but has not been investigated in patients with schizophrenia . Aims : To investigate effects from HIT on VO2peak , net mechanical efficiency of walking and risk factors for CVD in patients with schizophrenia . Methods : 25 in patients ( F20–29 , ICD-10 ) were allocated to either HIT or playing computer games ( CG ) , 3 days per week for 8 weeks . HIT consisted of 4 × 4-min intervals with 3-min break periods , at 85–95 % and 70 % of peak heart rate , respectively . Results : 12 and seven patients completed HIT and CG , respectively . The baseline VO2peak in both groups combined ( n = 19 ) was 36.8 ± 8.2 ml/kg/min and 3.12 ± 0.55 l/min . The HIT group improved VO2peak by 12 % from 3.17 ± 0.59 to 3.56 ± 0.68 l/min ( P < 0.001 ) , more than the CG group ( P = 0.014 ) . Net mechanical efficiency of walking improved by 12 % in the HIT group from 19.8 ± 3.0 % to 22.2 ± 4.5 % ( P = 0.005 ) , more than the CG group ( P = 0.031 ) . The psychiatric symptoms , expressed as the Positive and Negative Syndrome Scale ( PANSS ) and the Calgary Depression Scale for Schizophrenia ( CDSS ) , did not improve in either group . Conclusions : VO2peak and net mechanical efficiency of walking improved significantly by 8 weeks of HIT . HIT should be included in rehabilitation in order to improve physical capacity and contribute risk reduction of CVD BACKGROUND Interval ( IT ) and continuous training ( CT ) represent well-established exercise modalities in patients with moderate to severe chronic obstructive pulmonary disease ( COPD ) . However , their effects and feasibility in patients with end-stage COPD remain unclear . METHODS Sixty patients ( 53 ± 6 years , 53 % women ) being evaluated for lung transplantation where r and omly assigned either to IT ( n = 30 , cycling at 100 % peak work rate for 30 seconds alternating with 30 seconds of rest ) or CT ( n = 30 , cycling at 60 % of peak work rate ) during a 3-week inpatient rehabilitation program . Both exercise protocol s yielded an equivalent amount of total work . Patients had a mean forced expiratory volume at 1 second ( FEV(1 ) ) of 25 % ± 8 % of predicted value . RESULTS Patients in both groups achieved similar clinical ly relevant improvements in 6-minute walking distance of 35 ± 29 meters for IT and 36 ± 43 meters for CT , with a between-group difference of 0.3 meters ( 95 % confidence interval , -18.2 to 18.8 ) . Changes in lung function parameters were not significant . Perceived intensity of dyspnea was significantly ( p < 0.05 ) lower in IT ( Borg 6.2 ± 1.8 ) compared with CT ( Borg 7.1 ± 1.7 ) . Patients required a median of 5 unintended breaks ( interquartile range , 2 - 28 ) during IT exercise and 29 ( interquartile range , 6 - 68 ) during CT ( p < 0.001 ) . CONCLUSIONS IT is associated with a lower intensity of dyspnea during exercise and fewer unintended breaks but achieves similar improvements in exercise capacity compared with CT in pre-lung transplant COPD patients Objective Peak oxygen uptake ( VO2peak ) is a strong predictor of survival in cardiac patients . The aims of this study were to compare the effects of high interval training ( HIT ) to moderate continuous training ( MCT ) on VO2peak and to identify the safety of HIT in acute myocardial infa rct ion patients with drug-eluting stent . Design Twenty-eight acute myocardial infa rct ion patients with drug-eluting stent were r and omized to either HIT at 85%–95 % of heart rate reserve or MCT at 70%–85 % of heart rate reserve , 3 days a week for 6 wks at a cardiac rehabilitation clinic . Primary outcome was VO2peak at baseline and after cardiac rehabilitation . Results Both HIT and MCT groups showed significant increases in VO2peak and heart rate recovery after 6 wks of training . The 22.16 % improvement in VO2peak in the HIT group was significantly greater than the 8.48 % improvement in the MCT group ( P = 0.021 ) . There were no cardiovascular events related to both HIT and MCT . Conclusions HIT is more effective than MCT for improving VO2peak in acute myocardial infa rct ion patients with drug-eluting stent . These findings may have important implication s for more effective exercise training in cardiac rehabilitation program Purpose Peak oxygen consumption ( VO2peak ) is an important predictive factor for long-term prognosis in patients with non-small cell lung cancer ( NSCLC ) . The purpose of this study was to investigate whether 8 weeks of exercise training improves exercise capacity , as assessed by VO2peak , and other related factors in patients with NSCLC receiving targeted therapy . Methods A total of 24 participants with adenocarcinoma were r and omly assigned to either the control group ( n = 11 ) or the exercise group ( n = 13 ) . Subjects in the exercise group participated in individualized , high-intensity aerobic interval training of exercise . The outcome measures assessed at baseline and after 8 weeks were as follows : VO2peak and the percentage of predicted VO2peak ( % predVO2peak ) , muscle strength and endurance of the right quadriceps , muscle oxygenation during exercise , insulin resistance as calculated by the homeostasis model , high-sensitivity C-reactive protein , and quality of life ( QoL ) question naire inventory . Results No exercise-related adverse events were reported . After exercise training , VO2peak and % predVO2peak increased by 1.6 mL kg−1 min−1 and 5.3 % ( p < 0.005 ) , respectively ; these changes were associated with improvements in circulatory , respiratory , and muscular functions at peak exercise ( all p = 0.001 ) . The exercise group also had less dyspnea ( p = 0.01 ) and favorably lower fatigue ( p = 0.05 ) than baseline . Conclusions Patients with NSCLC receiving targeted therapy have quite a low exercise capacity , even with a relatively high QoL. Exercise training appears to improve exercise capacity and alleviate some cancer-related symptoms OBJECTIVE To estimate the minimal clinical ly important difference ( MCID ) for the 6-minute walk test ( 6MWT ) and the 200-m fast-walk test ( FWT ) in patients with coronary artery disease ( CAD ) during a cardiac rehabilitation program . DESIGN Prospect i ve study using distribution- and anchor-based methods . SETTING Out patients from a cardiac rehabilitation unit . PARTICIPANTS Stable patients with CAD ( N=81 ; 77 men ; mean±SD age , 58.1±8.7y ) enrolled 31±12.1 days after an acute coronary syndrome ( ACS ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES 6MWT and 200-m FWT results before and after an 8-week cardiac rehabilitation program and at the 6th and 12th sessions . Patients and physiotherapists who supervised the training were asked to provide a global rating of perceived change in walking ability while blinded to changes in walk test performances . RESULTS Mean change in 6MWT distance ( 6MWD ) in patients who reported no change was -6.5 m versus 23.3 m in those who believed their performance had improved ( P<.001 ) . This result was consistent with the MCID determined by using the distribution method ( 23 m ) . Considering a 25-m cutoff , positive and negative predictive values were 0.9 and .63 , respectively . Conversely , there was no difference in 200-m FWT performance between these 2 groups ( 0.1 vs -1.4s , respectively ) . There was poor agreement with the physiotherapist 's perceived change . CONCLUSIONS The MCID for 6MWD in patients with CAD after ACS was 25 m . This result will help physicians interpret 6MWD change and help research ers estimate sample sizes in further studies using 6MWD as an endpoint Context Exercise training improves quality of life in patients with chronic obstructive pulmonary disease , but many of these patients can not tolerate continuous exercise . The effects of intermittent exercise are not known . Contribution The authors r and omly assigned 100 in patients with chronic obstructive pulmonary disease in a 3-week respiratory rehabilitation program to receive either high-intensity continuous exercise or high-intensity exercise alternating with low-intensity exercise ( interval exercise ) . After 5 weeks , the 2 groups had similar respiratory symptoms in daily activities and 6-minute walking distance , but the interval exercise group adhered better to the exercise protocol . Caution s The study focused on initiation of exercise and not on outpatient or home-based maintenance of exercise . Implication s For pulmonary rehabilitation , interval exercise is as effective as continuous high-intensity exercise and is better tolerated . The Editors Low exercise capacity is an important systemic manifestation of advanced chronic obstructive pulmonary disease ( COPD ) associated with poor health-related quality of life , exacerbations , and death ( 14 ) . Physical exercise , therefore , represents an important element of COPD management ( 5 , 6 ) . If performed under supervision during respiratory rehabilitation , exercise training improves health-related quality of life and may improve prognosis ( 79 ) . Dyspnea and leg fatigue limit the ability of patients with COPD to exercise , and patient response to exercise is highly variable ( 10 ) . It is challenging to find endurable exercise programs that are still effective . Current guidelines recommend endurance exercise at constant and high intensity ( 70 % of maximum exercise capacity ) ( 11 , 12 ) . For example , if a patient achieves 100 watts in an incremental exercise test , workload would be set at 70 watts for the entire exercise session of at least 20 minute 's duration . Strong evidence from r and omized trials shows that patients achieve clinical ly important improvements of health-related quality of life and exercise capacity with a continuous exercise protocol ( 1316 ) . However , patients with severe COPD are often unable to tolerate continuous exercise ( 17 ) , which can be frustrating for them and can limit their long-term adherence to exercise programs . Effective alternatives to continuous exercise are required to offer this important intervention to more patients with COPD . The American Thoracic Society and the European Respiratory Society state , on the basis of 2 r and omized trials ( 18 , 19 ) , that interval exercise may be an alternative . The benefits of interval exercise may be similar to those of continuous training , but this method is associated with less dyspnea ( 11 , 12 ) . Although studies indicated that interval exercise is well tolerated ( 1821 ) , evidence about its effectiveness relative to continuous exercise is inconclusive ; previous trials had method ological limitations and were small ( 22 ) . Because of perceived better tolerability of interval exercise , r and omized trials should be explicitly design ed to show that interval exercise is no less effective ( clinical noninferiority ) ( 22 ) . Thus , the aim of our trial was to assess whether interval exercise is no less effective than high-intensity continuous exercise in patients with severe COPD and whether patient tolerance of the interval exercise protocol is superior to that of continuous exercise . Methods Design Overview We conducted a r and omized , controlled noninferiority trial to compare the effects of interval exercise with those of high-intensity continuous exercise in patients with severe COPD . We previously described the detailed study protocol ( 23 ) and report this trial following the recommendations of the extended Consoli date d St and ards of Reporting Trials ( CONSORT ) statement for noninferiority and equivalence trials ( 24 ) . Setting The trial took place in a public rehabilitation clinic , Klinik Barmelweid , in Aargau , Switzerl and . The ethics committee of the Kantonsspital Aarau , Aargau , Switzerl and , approved the study protocol , and all study participants provided written informed consent . Participants We screened patients admitted to the respiratory medicine unit and included consecutive patients following inclusion criteria similar to those of previous respiratory rehabilitation trials ( 7 ) : COPD as defined by FEV1FVC ratio less than 70 % of predicted , FEV1 less than 50 % of predicted after bronchodilation corresponding to Global Initiative for Chronic Obstructive Lung Disease ( GOLD ) stage III to IV ( 5 ) , and German as first or daily language . Exclusion criteria included cardiovascular , musculoskeletal , or neurologic disorders that inhibited physical exercise or the performance of exercise tests ( 6 ) . We also excluded patients who had received a diagnosis of cancer ( excluding skin cancer ) within the past 2 years and were undergoing treatment . R and omization and Interventions A third party not involved in the execution of the trial ( DatInf GmbH , Tuebingen , Germany ) provided online central r and omization using a computerized minimization procedure , thereby ensuring concealment of r and omization ( 25 ) . Stratification variables were exercise capacity ( 6-minute walking distance < 300 or 300 meters ) , the presence of affective disorders ( Hospital Anxiety Depression Scale scores < or 8) , stability of pulmonary condition ( stable or exacerbation within the last 8 weeks ) , and the need for oxygen at rest ( Pao 2 < 55 mm Hg or 55 mm Hg ) . Patients followed an inpatient respiratory rehabilitation of approximately 3 week 's duration that included 12 to 15 exercise sessions . On weekdays , patients usually participated in 1 exercise session . Twelve physical therapists worked with an approximately equal number of patients from both treatment groups . Apart from exercise , the rehabilitation program was identical for both groups and included breathing therapy , relaxation therapy , guided walking tours , and patient education ( 23 ) . At discharge , physiotherapists prescribed home-based exercise for each patient . Patients with cycle ergometers at home were instructed to exercise for at least 20 minutes per day . If no cycle ergometers were available , daily walking , swimming , or stair climbing was prescribed . High-Intensity Continuous Exercise Patients r and omly assigned to this intervention exercised on electromagnetically braked cycle ergometers ( Ergometrics 900S , Ergoline , Bitz , Germany ) with a target workload of 70 % or more of maximum exercise capacity ( Figure 1 ) . This exercise protocol has been used in earlier respiratory rehabilitation trials ( 7 ) . To determine maximum exercise capacity , patients pedaled unloaded for 3 minutes at 20 watts to warm up . Then , we used increments of 7.5 watts per minute until patients had to stop because of symptoms or cardiovascular stopping criteria . In each exercise session , patients completed a warm-up period of 2 minutes at 20 % of maximum exercise capacity , high-intensity exercise for 20 minutes , and a run-out phase of 2 minutes ( gradual decrease from 70 % to 0 % ) . If patients could not sustain the workload because of perceived dyspnea ( modified Borg [ 26 ] ratings > 5 on a scale from 0 to 10 ) or because heart rate exceeded safety limits , physical therapists let patients rest for 1 minute before continuing in the assigned phase . If patients had to rest more than twice per session , physical therapists lowered the workload by steps of 10 % of baseline maximum exercise capacity for the following exercise sessions . If workload was too low ( modified Borg ratings < 3 or patients or physical therapists considered the workload to be too low ) , physical therapists increased the workload by steps of 10 % of baseline maximum exercise capacity . Figure 1 . Exercise protocol s. Interval Exercise The target workload for this group was 50 % ( high-intensity intervals ) and 10 % ( low-intensity intervals ) of short-term maximum exercise capacity as determined by a steep ramp test ( 27 , 28 ) . The steep ramp test is an incremental cycle ergometer test in which patients pedal cycle ergometers unloaded for 2 minutes and then at increments of 25 watts every 10 seconds until they can not maintain a pedaling frequency above 50 pedals per minute or their heart rate exceeds the limit set by the normal incremental exercise test . We used the steep ramp test because workload for interval exercise can be underestimated if it is based on normal incremental exercise tests ( 28 ) . Fifty percent of short-term maximum exercise capacity corresponds , on average , to 90 % to 100 % of normal maximum exercise capacity ( 27 ) . We chose a workrecovery ratio of 1:2 that prevents high lactate accumulation and is well tolerated by patients ( 28 ) . In each session , patients had a warm-up period of 2 minutes at 10 % of the short-term maximum exercise capacity and then exercised for 20 minutes alternating between high-intensity intervals for 20 seconds and low-intensity intervals for 40 seconds ( Figure 1 ) . Patients also had a slowdown period of 2 minutes before completing the training session . We adjusted the exercise load for each patient individually if workload was too high or too low as described earlier ; physiotherapists lowered or increased the workload by steps of 10 % of short-term maximum exercise capacity , but the length of intervals remained constant ( 23 ) . Outcomes and Measurements Our primary outcome for effectiveness was the difference from baseline in Chronic Respiratory Question naire ( CRQ ) scores 5 weeks after r and omization as measured by the self-administered German- language version ( 29 , 30 ) with st and ardized dyspnea questions ( 31 ) . The CRQ is a widely used instrument in respiratory rehabilitation and measures dyspnea , fatigue , emotional functioning , and ability to cope with COPD ( 7 , 32 ) . Domain and total ( average of domains ) scores are presented on a Likert-type scale from 1 ( most severe impairment ) to 7 ( no impairment ) . We selected assessment at 5 weeks after r and omization as the primary outcome Aims . High-intensity interval training ( HIIT ) leads to improvements in various markers of cardiometabolic health but adherence to HIIT following a supervised laboratory intervention has yet to be tested . We compared self-report and objective measures of physical activity after one month of independent exercise in individuals with prediabetes who were r and omized to HIIT ( n = 15 ) or traditional moderate-intensity continuous training ( MICT , n = 17 ) . Method . After completing 10 sessions of supervised training participants were asked to perform HIIT or MICT three times per week for four weeks . Results . Individuals in HIIT ( 89 ± 11 % ) adhered to their prescribed protocol to a greater extent than individuals in MICT ( 71 ± 31 % ) as determined by training logs completed over one-month follow-up ( P = 0.05 , Cohen 's d = 0.75 ) . Minutes spent in vigorous physical activity per week measured by accelerometer were higher in HIIT ( 24 ± 18 ) as compared to MICT ( 11 ± 10 ) at one-month follow-up ( P = 0.049 , Cohen 's d = 0.92 ) . Cardiorespiratory fitness and systolic blood pressure assessed at one-month follow-up were equally improved ( P 's < 0.05 ) . Conclusions . This study provides preliminary evidence that individuals with prediabetes can adhere to HIIT over the short-term and do so at a level that is greater than MICT Patients with substance use disorder ( SUD ) suffer a higher risk of cardiovascular disease and other lifestyle diseases compared to the general population . High intensity training has been shown to effectively reduce this risk , and therefore we aim ed to examine the feasibility and effect of such training in SUD patients in clinical treatment in the present study . 17 males and 7 females ( 32 ± 8 yr ) in treatment were r and omized to either a training group ( TG ) , treadmill interval training in 4 × 4 minutes at 90–95 % of maximal heart rate , 3 days a week for 8 weeks , or a conventional rehabilitation control group ( CG ) . Baseline values for both groups combined at inclusion were 44 ± 8 ( males ) and 34 ± 9 ( females ) mL · min−1 · kg−1 , respectively . 9/12 and 7/12 patients completed the TG and CG , respectively . Only the TG significantly improved ( 15 ± 7 % ) their maximal oxygen consumption ( VO2max ) , from 42.3 ± 7.2 mL · min−1 · kg−1 at pretest to 48.7 ± 9.2 mL · min−1 · kg−1 at posttest . No between-group differences were observed in work economy , and level of insomnia ( ISI ) or anxiety and depression ( HAD ) , but a significant within-group improvement in depression was apparent for the TG . High intensity training was feasible for SUD patients in treatment . This training form should be implemented as a part of the rehabilitation since it , in contrast to the conventional treatment , represents a risk reduction for cardiovascular disease and premature death Abstract To compare the effects of a 3‐week multimodal rehabilitation involving supervised high‐intensity interval training ( HIIT ) on female breast cancer survivors with respect to key variables of aerobic fitness , body composition , energy expenditure , cancer‐related fatigue , and quality of life to those of a st and ard multimodal rehabilitation program . A r and omized controlled trial design was administered . Twenty‐eight women , who had been treated for cancer were r and omly assigned to either a group performing exercise of low‐to‐moderate intensity ( LMIE ; n = 14 ) or a group performing high‐intensity interval training ( HIIT ; n = 14 ) as part of a 3‐week multimodal rehabilitation program . No adverse events related to the exercise were reported . Work economy improved following both HIIT and LMIE , with improved peak oxygen uptake following LMIE . HIIT reduced mean total body fat mass with no change in body mass , muscle or fat‐free mass ( best P < 0.06 ) . LMIE increased muscle and total fat‐free body mass . Total energy expenditure ( P = 0.45 ) did not change between the groups , whereas both improved quality of life to a similar high extent and lessened cancer‐related fatigue . This r and omized controlled study demonstrates that HIIT can be performed by female cancer survivors without adverse health effects . Here , HIIT and LMIE both improved work economy , quality of life and cancer‐related fatigue , body composition or energy expenditure . Since the outcomes were similar , but HIIT takes less time , this may be a time‐efficient strategy for improving certain aspects of the health of female cancer survivors Twenty-six adults ( 23 to 58 years ) with mild to moderate asthma underwent a 10-week supervised rehabilitation program , with emphasis on physical training . In the first 2 weeks , they exercised daily in an indoor swimming pool ( 33 degrees C ) and received education about asthma , medication , and principles of physical training . In the following 8 weeks , they exercised in the pool twice a week . Every training session lasted 45 min . The training sessions were made as suitable as possible for the individual subjects , in order to minimize " drop outs " from the program . The aim of the study was to evaluate the efficacy of the rehabilitation program and to determine if inactive asthmatic adults can exercise at high intensity . The rehabilitation program was preceded by a 6-min submaximal cycle ergometry test , a 12-min walking test , spirometry , and a methacholine provocation test . The subjects also responded to a five-item question naire related to anxiety about exercise , breathlessness , and asthma symptoms using a visual analogue scale . All subjects were able to perform physical training at a very high intensity , to 80 to 90 % of their predicted maximal heart rate . No asthmatic attacks occurred in connection with the training sessions . Twenty-two of the 26 subjects completed the rehabilitation program , felt confident with physical training , and planned to continue regular physical training after the 10-week program . Improvements in cardiovascular conditioning , measured as a decreased heart rate at the same load on the cycle ergometer ( average of 12 beats/min ) , and as a longer distance at the 12-min walking test ( average of 111 m ) , were observed during the program . FEV1 increased significantly from 2.2 to 2.5 L. Forced expiratory flow at 25 % of vital capacity also increased slightly but significantly . Methacholine provocation dose causing a fall in FEV1 by 20 % was unchanged . Seventeen subjects had a peak expiratory flow reduction of more than 15 % after the preprogram ergometry test and were classified as having exercise-induced asthma ( EIA ) . Only three of these subjects had EIA after 10 weeks . The asthmatic subjects were less afraid of experiencing breathlessness during exercise and less anxious about exercising at a high intensity after 10 weeks ( p < 0.05 ) . The asthma symptoms abated significantly during the rehabilitation program and the subjects needed less acute asthma care after the rehabilitation program . The results indicate that asthmatic persons benefit from a rehabilitation period , including physical training . Rehabilitation programs are therefore of value as a supplement to conventional pharmacologic treatment of asthma . This rehabilitation program can be adapted for use in clinical practice Very high-intensity , low-volume , sprint interval training ( SIT ) increases muscle oxidative capacity and may increase maximal oxygen uptake ( $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ ) , but whether circulatory function is improved , and whether SIT is feasible in overweight/obese women is unknown . To examine the effects of SIT on $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ and circulatory function in sedentary , overweight/obese women . Twenty-eight women with BMI > 25 were r and omly assigned to SIT or control ( CON ) groups . One week before pre-testing , subjects were familarized to $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ testing and the workload that elicited 50 % $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ was calculated . Pre- and post-intervention , circulatory function was measured at 50 % of the pre-intervention $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ , and a GXT was performed to determine $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ . During the intervention , SIT training was given for 3 days/week for 4 weeks . Training consisted of 4–7 , 30-s sprints on a stationary cycle ( 5 % body mass as resistance ) with 4 min active recovery between sprints . CON maintained baseline physical activity . Post-intervention , heart rate ( HR ) was significantly lower and stroke volume ( SV ) significantly higher in SIT ( −8.1 and 11.4 % , respectively ; P < 0.05 ) during cycling at 50 % $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ ; changes in CON were not significant ( 3 and −4 % , respectively ) . Changes in cardiac output ( $ $ { \dot{\text{Q } } } $ $ ) and arteriovenous oxygen content difference [ ( a − v)O2 diff ] were not significantly different for SIT or CON . The increase in $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ by SIT was significantly greater than by CON ( 12 vs. −1 % ) . Changes by SIT and CON in HRmax ( −1 vs. −1 % ) were not significantly different . Four weeks of SIT improve circulatory function during submaximal exercise and increases $ $ { \dot{V}\text{O } } _ { { 2 { \text{max } } } } $ $ in sedentary , overweight/obese women OBJECTIVE To compare the effects of an 8-week , high-intensity interval training protocol versus continuous training . DESIGN R and omized controlled trial . SETTING Cardiac rehabilitation center . PARTICIPANTS Patients ( N=26 ; mean age ± SD , 54±12y ) with chronic heart failure were enrolled in a cardiac rehabilitation program for 8 weeks . INTERVENTIONS Patients were r and omly assigned into 2 groups that performed either interval training ( IT ) or continuous training ( CT ) . IT consisted of 3 sessions of 12 repetitions of 30 seconds of exercise at very high intensity , followed by 60 seconds of complete rest . The CT group performed CT exercises , which consisted of 45 minutes of aerobic exercise . MAIN OUTCOME MEASURES Parameters of gas exchanges : peak oxygen consumption ( Vo(2)peak ) , first ventilator threshold ( VT1 ) , distance at six-minute walk test ( 6MWT ) , and level of anxiety and depression were measured . RESULTS The IT group increased significantly their Vo(2)peak , the duration of the exercise test , the oxygen pulse , oxygen consumption at the VT1 , and the distance walked during the 6MWT . The CT group only increased the time at the VT1 and the distance performed at the 6MWT . The improvement in the time at the VT1 was significantly higher for the IT group than for the CT group . CONCLUSIONS This study shows that IT at very high intensity for patients with heart failure appears to be more effective than CT in improving indices of submaximal exercise capacity BACKGROUND Neoadjuvant chemotherapy ( NAC ) followed by surgery for resectable oesophageal or gastric cancer improves outcome when compared with surgery alone . However NAC has adverse effects . We assess here whether NAC adversely affects physical fitness and whether such an effect is associated with impaired survival following surgery . METHODS We prospect ively studied 116 patients with oesophageal or gastric cancer to assess the effect of NAC on physical fitness , of whom 89 underwent cardiopulmonary exercise testing ( CPET ) before NAC and proceeded to surgery . 39 patients were tested after all cycles of NAC but prior to surgery . Physical fitness was assessed by measuring oxygen uptake ( VO₂ in ml kg(-1 ) min(-1 ) ) at the estimated lactate threshold ( θL ) and at peak exercise ( VO₂ peak in ml kg(-1 ) min(-1 ) ) . RESULTS VO₂ at θL and at peak were significantly lower after NAC compared to pre-NAC values : VO₂ at θL 14.5 ± 3.8 ( baseline ) vs. 12.3 ± 3.0 ( post-NAC ) ml kg(-1 ) min(-1 ) ; p ≤ 0.001 ; VO₂ peak 20.8 ± 6.0 vs. 18.3 ± 5.1 ml kg(-1 ) min(-1 ) ; p ≤ 0.001 ; absolute VO₂ ( ml min(-1 ) ) at θL and peak were also lower post-NAC ; p ≤ 0.001 . Decreased baseline VO₂ at θL and peak were associated with increased one year mortality in patients who completed a full course of NAC and had surgery ; p = 0.014 . CONCLUSION NAC before cancer surgery significantly reduced physical fitness in the overall cohort . Lower baseline fitness was associated with reduced one-year-survival in patients completing NAC and surgery , but not in patients who did not complete NAC . It is possible that in some patients the harms of NAC may outweigh the benefits . Trials Registry Number : NCT01335555 Purpose Following colorectal cancer diagnosis and anti-cancer therapy , declines in cardiorespiratory fitness and body composition lead to significant increases in morbidity and mortality . There is increasing interest within the field of exercise oncology surrounding potential strategies to remediate these adverse outcomes . This study compared 4 weeks of moderate-intensity exercise ( MIE ) and high-intensity exercise ( HIE ) training on peak oxygen consumption ( V̇O2peak ) and body composition in colorectal cancer survivors . Methods Forty seven post-treatment colorectal cancer survivors ( HIE = 27 months post-treatment ; MIE = 38 months post-treatment ) were r and omised to either HIE [ 85–95 % peak heart rate ( HRpeak ) ] or MIE ( 70 % HRpeak ) in equivalence with current physical activity guidelines and completed 12 training sessions over 4 weeks . Results HIE was superior to MIE in improving absolute ( p = 0.016 ) and relative ( p = 0.021 ) V̇O2peak . Absolute ( + 0.28 L.min−1 , p < 0.001 ) and relative ( + 3.5 ml.kg−1.min−1 , p < 0.001 ) V̇O2 peak were increased in the HIE group but not the MIE group following training . HIE led to significant increases in lean mass ( + 0.72 kg , p = 0.002 ) and decreases in fat mass ( −0.74 kg , p < 0.001 ) and fat percentage ( −1.0 % , p < 0.001 ) , whereas no changes were observed for the MIE group . There were no severe adverse events . Conclusions In response to short-term training , HIE is a safe , feasible and efficacious intervention that offers clinical ly meaningful improvements in cardiorespiratory fitness and body composition for colorectal cancer survivors . Implication s for Cancer SurvivorsHIE appears to offer superior improvements in cardiorespiratory fitness and body composition in comparison to current physical activity recommendations for colorectal cancer survivors and therefore may be an effective clinical utility following treatment Background Poststroke guidelines recommend moderate-intensity , continuous aerobic training ( MCT ) to improve aerobic capacity and mobility after stroke . High-intensity interval training ( HIT ) has been shown to be more effective than MCT among healthy adults and people with heart disease . However , HIT and MCT have not been compared previously among people with stroke . Objective The purpose of this study was to assess the feasibility and justification for a definitive r and omized controlled trial ( RCT ) comparing HIT and MCT in people with chronic stroke . Design A preliminary RCT was conducted . Setting The study was conducted in a cardiovascular stress laboratory and a rehabilitation research laboratory . Patients Ambulatory people at least 6 months poststroke participated . Intervention Both groups trained 25 minutes , 3 times per week , for 4 weeks . The HIT strategy involved 30-second bursts at maximum-tolerated treadmill speed alternated with 30- to 60-second rest periods . The MCT strategy involved continuous treadmill walking at 45 % to 50 % of heart rate reserve . Measurements Measurements included recruitment and attendance statistics , qualitative HIT acceptability , adverse events , and the following blinded outcome variables : peak oxygen uptake , ventilatory threshold , metabolic cost of gait , fractional utilization , fastest treadmill speed , 10-Meter Walk Test , and Six-Minute Walk Test . Results During the 8-month recruitment period , 26 participants consented to participate . Eighteen participants were enrolled and r and omly assigned to either the HIT group ( n=13 ) or the MCT group ( n=5 ) . Eleven out of the 13 HIT group participants attended all sessions . Participants reported that HIT was acceptable and no serious adverse events occurred . St and ardized effect size estimates between groups were moderate to very large for most outcome measures . Only 30 % of treadmill speed gains in the HIT group translated into overground gait speed improvement . Limitations The study was not design ed to definitively test safety or efficacy . Conclusions Although further protocol optimization is needed to improve overground translation of treadmill gains , a definitive RCT comparing HIT and MCT appears to be feasible and warranted PURPOSE The purpose of this study was to compare the effects of interval training ( IT ) and continuous steady-pace training ( CT ) in patients with COPD . METHODS Patients ( n = 21 ) ( mean forced expiratory volume in 1 second ( [ FEV1 ] = 44.6 % ± 13.9 % ) were r and omized to IT , and 20 patients ( mean FEV1 = 41.7 % ± 12.6 % ) to CT . Outcome measures included 6-minute walk distance , maximal work capacity , endurance exercise time during constant workload exercise at 60 % to 70 % of maximal work capacity , and quality of life including fatigue and dyspnea . Participants exercised 3 times per week for 8 weeks , and total work was the same for both training regimens . RESULTS Significant improvement in mean score was observed in each variable within each of the 2 groups : 6-minute walk distance ( IT = 158 ± 178 ft , CT = 106 ± 165 ft ) ; maximal work capacity ( IT = 10.0 ± 13.0 W , CT = 11.5 ± 13.1 W ) ; endurance exercise time ( IT = 15.0 ± 12.5 minutes , CT = 18.7 ± 10.6 minutes ) ; and quality of life domains , fatigue ( IT = 3.1 ± 3.0 , CT = 2.8 ± 4.7 ) , and dyspnea ( IT = 4.4 ± 5.3 , CT = 5.4 ± 5.1 ) . There was no significant difference in the extent of improvement between the 2 training regimens for any of the outcome variables . CONCLUSION Compared with CT , IT was well tolerated and produced similar improvements in exercise performance and quality of life INTRODUCTION In this prospect i ve r and omized trial , we examined the effect of three popular exercise training modalities on maximal oxygen uptake ( V˙O2max ) in overweight and obese individuals . In addition , we examined possible concomitant adaptations in endurance exercise performance ( time to exhaustion ( TTE ) ) , citrate synthase ( CS ) activity , venous and arterial function , blood volume , and calculated stroke volume ( SV ) . METHODS Thirty subjects were recruited ( age , 41 ± 9 yr ; weight , 91 ± 14 kg ; height , 173 ± 8 cm ; body mass index , 30 ± 4 kg·m(-2 ) ) and r and omized to either 6 wk of 4 × 4-min high-intensity interval training ( 4HIIT ) at 85%-95 % of HRmax , 10 × 1-min HIIT ( 1HIIT ) at V˙O2max load , or 45-min moderate-intensity continuous training ( MICT ) at 70 % of HRmax . V˙O2max , TTE , CS activity , venous and arterial function , as well as blood volume were measured before and after the training period . O2 pulse was calculated and used to estimate SV . Analysis was conducted per protocol . RESULTS Only 4HIIT increased V˙O2max ( P < 0.01 ) and significantly more compared with 1HIIT ( P = 0.04 ) and MICT ( P = 0.03 ) ( 4HIIT , 10 % ; 1HIIT , 3.3 % ; and MICT , 3.1 % ) . All groups increased TTE ( 4HIIT , 198 % ; 1HIIT , 116 % ; MICT , 52 % ) , with a higher increase after 4HIIT compared with that after MICT ( P = 0.02 ) . Calculated SV increased only after 4HIIT ( 14.4 % ) . Plasma volume and hemoglobin mass increased after 1HIIT only ( 5.6 % and 6.5 % ) ; however , no group differences were found . All groups increased CS activity ( 4HIIT , 35 % ; 1HIIT , 35 % ; MICT , 56 % ) , with no group differences . Arterial inflow ( 15.7 % ) and venous outflow ( 22.7 % ) decreased after MICT , but there were no group differences . CONCLUSIONS 4HIIT was superior to 1HIIT and MICT in improving V˙O2max likely because of an increased SV Background Exercise therapy is being explored in a variety of cancer population s to counteract treatment-related deconditioning . Higher intensity interval protocol s are being prescribed to improve physical function and attenuate surrogates of comorbidity in non-cancer population s. The purpose of this study is to explore the safety of higher intensity exercise stimuli on cardiorespiratory fitness ( VO2peak ) in breast cancer survivors . Methods Postmenopausal breast cancer survivors were r and omized into three groups : supervised aerobic interval training ( AIT ) , supervised continuous moderate exercise training ( CMT ) , and an unsupervised control group ( CON ) . For 6 weeks , AIT exercised between 70 and 100 % VO2peak , while CMT exercised between 60 and 70 % VO2peak . Both groups followed a matched-work design . Results Thirty-three participants completed the study ( age , 57.2 ( 9 ) years ; weight , 67.6 ( 12 ) kg ) with no adverse advents . Between-group baseline values were non-significant . VO2peak at baseline ( 25.3 ( 5.4 ) mL·kg−1·min−1 ) was below population norms . Compared to CON , cardiorespiratory fitness improved in AIT and CMT by 12 % ( P < 0.001 ) with no significant difference between exercise groups . AIT had a greater influence on lower extremity strength ( P = 0.026 ) and body weight ( P = 0.031 ) . Conclusion This pilot study provides evidence that similar to CMT , AIT can safely increase VO2peak in a small group of breast cancer survivors . Further exploration of the benefits of implementing higher intensity training protocol s is warranted Background High-intensity interval training has recently emerged as superior to continuous endurance training in cardiac rehabilitation upon other training regimes . Individually tailored continuous endurance training and pyramid training could induce comparable effects on peak work capacity as high intensity interval training . Design A prospect i ve , r and omized study . Methods Effects of the following isocaloric cycle ergometer protocol s on peak work capacity have been assessed in patients with coronary artery disease ( n = 60 ) during 6 weeks of outpatient cardiac rehabilitation , i.e. 18 supervised sessions of exercise training : ( 1 ) continuous endurance training ( n = 20 ) : 33 min at 65–85 % peak heart rate ; ( 2 ) high intensity interval training ( n = 20 ) : 4 × 4 min intervals at 85–95 % peak heart rate , each followed by 3 min of active recovery at 60–70 % peak heart rate ; ( 3 ) pyramid training ( n = 20 ) : 3 × 8 min of stepwise load increase and subsequent decrease from 65–95–65 % peak heart rate , supplemented by 2 min recovery at 60–70 % peak heart rate between pyramids . All protocol s were preceded by 5 min of warm-up and followed by 5 min cool-down at 60–70 % peak heart rate . Results Attendance during exercise sessions was 99.2 % . There were significant increases in peak work capacity of comparable magnitude in all three training groups ( begin vs. end : continuous endurance training : 136.0 ± 49.6 W vs. 163.4 ± 60.8 W ( 21.1 ± 8.5 % ) ; high-intensity interval training : 141.0 ± 60.4 W vs. 171.1 ± 69.8 W ( 22.8 ± 6.6 % ) ; pyramid training : 128.7 ± 50.6 W vs. 158.5 ± 57.9 W ( 24.8 ± 10.8 % ) ; within groups all p < 0.001 ; between groups , p = not significant ) . Conclusion Endurance training protocol s assessed in this study all led to significant increases in peak work capacity of comparable magnitude . Our findings suggest that these protocol s can be used interchangeably , which will lead to further individualization of exercise prescription and may therefore result in improved adherence to lifelong behavioural changes The purpose of the study was to examine the effects of sprint interval training ( SIT ) and moderate-intensity continuous cycle training ( MICT ) , with equal estimated energy expenditure during training on body composition and aerobic capacity . Body composition measured via dual-energy X-ray absorptiometry and aerobic capacity were assessed following 6 weeks of training in previously inactive overweight/obese young women ( n = 52 ; age , 20.4 ± 1.5 years ; body mass index , 30.3 ± 4.5 kg·m-2 , 67.3 % white ) . Training was performed in a group-exercise format that mimicked cycling classes offered by commercial fitness facilities , and included 3 weekly sessions of either 30-s " all-out " sprints followed by 4 min of active recovery ( SIT ) , or continuous cycling at 60%-70 % heart rate reserve to expend a similar amount of energy . Participants were r and omized to SIT or MICT , attended a similar number of sessions ( 15.0 ± 1.5 sessions vs. 15.8 ± 1.9 sessions , P = 0.097 ) and expended a similar amount of energy ( 541.8 ± 104.6 kJ·session-1 vs. 553.5 ± 138.1 kJ·session-1 , P = 0.250 ) . Without significant changes in body mass ( P > 0.05 ) , greater relative reductions occurred in SIT than in MICT in total fat mass ( 3.6 % ± 5.6 % vs. 0.6 % ± 3.9 % , P = 0.007 ) , and and roid fat mass ( 6.6 % ± 6.9 % vs. 0.7 % ± 6.5 % , P = 0.002 ) . Aerobic capacity ( mL·kg-1·min-1 ) increased significantly following both interventions ( P < 0.05 ) , but the relative increase was 2-fold greater in SIT than in MICT ( 14.09 % ± 10.31 % vs. 7.06 % ± 7.81 % , P < 0.001 ) . In conclusion , sprint-interval cycling reduces adiposity and increases aerobic capacity more than continuous moderate-intensity cycling of equal estimated energy expenditure in overweight/obese young women Background — A well-developed coronary collateral circulation provides a potential source of blood supply in coronary artery disease . However , the prognostic importance and functional relevance of coronary collaterals is controversial with the association between exercise training and collateral growth still unclear . Methods and Results — This prospect i ve , open-label study r and omly assigned 60 patients with significant coronary artery disease ( fractional flow reserve ⩽0.75 ) to high-intensity exercise ( group A , 20 patients ) or moderate-intensity exercise ( group B , 20 patients ) for 4 weeks or to a control group ( group C , 20 patients ) . The primary end point was the change of the coronary collateral flow index ( CFI ) after 4 weeks . Analysis was based on the intention to treat . After 4 weeks , baseline CFI increased significantly by 39.4 % in group A ( from 0.142±0.07 at beginning to 0.198±0.09 at 4 weeks ) in comparison with 41.3 % in group B ( from 0.143±0.06 to 0.202±0.09 ) , whereas CFI in the control group remained unchanged ( 0.7 % , from 0.149±0.09 to 0.150±0.08 ) . High-intensity exercise did not lead to a greater CFI than moderate-intensity training . After 4 weeks , exercise capacity , VO2 peak and ischemic threshold increased significantly in group A and group B in comparison with group C with no difference between group A and group B. Conclusions — A significant improvement in CFI was demonstrated in response to moderate- and high-intensity exercise performed for 10 hours per week . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01209637 Abstract Objectives . This study investigates the effect of aerobic interval training on diastolic function at rest and during exercise in stable heart transplant ( HTx ) recipients . Design . Twenty-three stable HTx recipients ( 74 % males , mean age 50 ± 14.9 years ) were recruited to a training programme . Intervention was 8 weeks intensive training or control in a r and omized controlled design . Results . At baseline , participants had normal or mild diastolic dysfunction at rest . During exercise , mean E/e′ increased from 9.0 ( ± 2.8 ) to 12.8 ( ± 7.7 ) ( p = 0.09 ) , E/A increased from 2.1 ( ± 0.6 ) to 2.6 ( ± 0.7 ) ( p = 0.02 ) , and deceleration time decreased by over 50 ms , all markers of increased filling pressure . There were no correlations between diastolic function and VO2peak at baseline . After intervention VO2peak increased from 23.9 ( ± 4.5 ) to 28.3(± 6 ) ml/kg/min in the training group ( difference between groups p = 0.0018 ) . No consistent pattern of improvement in diastolic function at rest or during exercise was seen . Conclusion . The study does not support a role of diastolic dysfunction in the limited exercise capacity of HTx recipients and suggests that in these patients peripheral factors are of greater importance Heart failure with preserved ejection fraction ( HFpEF ) is a major cause of morbidity and mortality . Exercise training is an established adjuvant therapy in heart failure ; however , the effects of high-intensity interval training ( HIIT ) in HFpEF are unknown . We compared the effects of HIIT vs. moderate-intensity aerobic continuous training ( MI-ACT ) on peak oxygen uptake ( V̇o₂peak ) , left ventricular diastolic dysfunction , and endothelial function in patients with HFpEF . Nineteen patients with HFpEF ( age 70 ± 8.3 yr ) were r and omized to either HIIT ( 4 × 4 min at 85 - 90 % peak heart rate , with 3 min active recovery ) or MI-ACT ( 30 min at 70 % peak heart rate ) . Fifteen patients completed exercise training ( HIIT : n = 9 ; MI-ACT : n = 6 ) . Patients trained 3 days/wk for 4 wk . Before and after training patients underwent a treadmill test for V̇o₂peak determination , 2D-echocardiography for assessment of left ventricular diastolic dysfunction , and brachial artery flow-mediated dilation ( FMD ) for assessment of endothelial function . HIIT improved V̇o₂peak ( pre = 19.2 ± 5.2 ml·kg(-1)·min(-1 ) ; post = 21.0 ± 5.2 ml·kg(-1)·min(-1 ) ; P = 0.04 ) and left ventricular diastolic dysfunction grade ( pre = 2.1 ± 0.3 ; post = 1.3 ± 0.7 ; P = 0.02 ) , but FMD was unchanged ( pre = 6.9 ± 3.7 % ; post = 7.0 ± 4.2 % ) . No changes were observed following MI-ACT . A trend for reduced left atrial volume index was observed following HIIT compared with MI-ACT ( -3.3 ± 6.6 vs. + 5.8 ± 10.7 ml/m(2 ) ; P = 0.06 ) . In HFpEF patients 4 wk of HIIT significantly improved V̇o₂peak and left ventricular diastolic dysfunction . HIIT may provide a more robust stimulus than MI-ACT for early exercise training adaptations in HFpEF Introduction : Impairment in aerobic fitness is a potential modifiable risk factor for postoperative complications . In this r and omized controlled trial , we hypothesized that a high‐intensity interval training ( HIIT ) program enhances cardiorespiratory fitness before lung cancer surgery and therefore reduces the risk of postoperative complications . Methods : Patients with operable lung cancer were r and omly assigned to usual care ( UC ) ( n = 77 ) or preoperative rehabilitation based on HIIT ( Rehab ) ( n = 74 ) . Maximal cardiopulmonary exercise testing and the 6‐minute walk test were performed twice before surgery . The primary outcome measure was a composite of death and in‐hospital postoperative complications . Results : The groups were well balanced in terms of patient characteristics . During the preoperative waiting period ( median 25 days ) , the peak oxygen consumption and the 6‐minute walking distance increased ( median + 15 % , interquartile range , 25th to 75 percentile [ IQR25%–75 % , % ] = + 9 % to + 22 % , p = 0.003 and + 15 % , IQR25%–75 % = + 8 % to + 28 % , p < 0.001 , respectively ) in the Rehab group , whereas peak oxygen consumption declined in the UC group ( median –8 % , IQR25%–75 % = –16 % to 0 % ] , p = 0.005 ) . The primary end point did not differ significantly between the two groups : at least one postoperative complication developed in 27 of the 74 patients ( 35.5 % ) in the Rehab group and 39 of 77 patients ( 50.6 % ) in the UC group ( p = 0.080 ) . Notably , the incidence of pulmonary complications was lower in the Rehab compared with in the UC group ( 23 % versus 44 % , p = 0.018 ) , owing to a significant reduction in atelectasis ( 12.2 % versus 36.4 % , p < 0.001 ) , and this decrease was accompanied by a shorter length of stay in the postanesthesia care unit ( median –7 hours , IQR25%–75 % = –4 to –10 ) . Conclusions : In this r and omized controlled trial , preoperative HIIT result ed in significant improvement in aerobic performances but failed to reduce early complications after lung cancer resection Coronary allograft vasculopathy is a well‐known long‐term complication after cardiac transplantation . Endothelial dysfunction is involved and may be prevented by aerobic exercise . The purpose of this study was to examine whether high intensity aerobic exercise improves peak oxygen uptake ( VO2 peak ) and endothelial function in heart transplant ( HT ) recipients . Twenty‐seven long‐term HT recipients were r and omized to either 8‐weeks high intensity aerobic exercise or no training . Flow mediated dilation of the brachial artery ( FMD ) was measured by ultrasound and VO2 peak by the analysis of expired air . Blood pressure and biomarkers were measured before and after 8 weeks . VO2 peak increased significantly in the exercise group ( VO2 peak 23.9 ± 1.79 to 28.3 ± 1.63 mL/kg/min compared to controls ( VO2 peak 24.6 ± 1.38 to 23.4 ± 1.58 , p < 0.001 exercise vs. control).FMD increased in the exercise group compared to controls ( 8.3 ± 1.1 % to 11.4 ± 1.2 % vs. 5.6 ± 1.0 % to 5.3 ± 1.7 % , p = 0.024 ) . No increase in nitroglycerin‐induced vasodilation was observed . Systolic blood pressure fell in the exercise group ( 142 ±4.2 mmHg to127 ± 3.4 mmHg , p = 0.01 ) and was unchanged in controls ( 141 ± 4.2 mmHg to 142 ±6.4 mmHg , NS ) . High intensity aerobic exercise reduces systolic blood pressure and improves endothelial function in HT recipients |
12,975 | 15,342,661 | Problem-based learning and evidence -based health care interventions increased student knowledge of medical topics and their ability to search , evaluate , and appraise medical literature .
Dental students in a problem-based learning curriculum , emphasizing evidence -based practice s , scored higher on the NDB I ( National Dentistry Boards , Part I ) than students in traditional curricula .
Considering the strength of evidence in the review ed literature , we concluded that an evidence -based approach to clinical care is effective | The objective of this project was to identify an effective methodology of approaching and implementing evidence -based principles in undergraduate teaching clinics to promote evidence -based dentistry in future clinical practice .
A systematic review was undertaken to examine evidence -based clinical teaching and faculty continuing education . | Previous papers in this series on evidence -based dentistry have discussed the first 2 steps in seeking answers to clinical problems formulating a clear question and strategically search ing for evidence . The next step , critical appraisal of the evidence , is made easier if one underst and s the basic concepts of clinical research design . The strongest design , especially for questions related to therapeutic or preventive interventions , is the r and omized , controlled trial . Questions relating to diagnosis , prognosis and causation are often studied with observational , rather than experimental , research design s. The strongest study design should be used whenever possible . Rules have been established to grade research evidence . This paper , the fourth in the series , presents an overview of research methodology most commonly used in the dental literature OBJECTIVES To compare learning outcomes and perceptions of facilitator behaviours and small-group process in problem-based learning ( PBL ) groups led by students and those led by faculty . DESIGN A prospect i ve , Latin-square cross-over design was employed . Second-year medical students participated in 11 PBL cases over the course of the academic year . For each case , half the student groups were led by faculty and the other half by a student group member selected r and omly to serve in the facilitator role . Learning outcomes were assessed by performance on objective examinations covering factual material s pertinent to the case . Perceptions of facilitator behaviours and of group functioning were assessed with a question naire completed at the end of each individual case . Focus-group discussion s were held to gain more in-depth information about student perceptions and experience . Student-led sessions were observed at r and om by the investigators . SETTING A state-supported , US medical school with a hybrid lecture-based and problem-based curriculum . SUBJECTS One hundred and twenty-seven second-year medical students and 30 basic science and clinical faculty . RESULTS No differences were detected in student performance on the objective evaluation based on whether the facilitator was a faculty member or peer group member , nor were there any differences in the perceptions of group process . Students gave peer facilitators slightly higher ratings in the second semester of the experiment . In the focus-group discussion s , students voiced a general preference for student-led groups because they felt they were more efficient . Observation and focus-group reports suggest that groups led by students sometimes took short cuts in the PBL process . CONCLUSION In a hybrid lecture- and PBL-based curriculum , student performance on objective examinations covering PBL material s is unaffected by the status of the facilitator ( student vs. faculty ) . However , in peer-facilitated groups , students sometimes took short cuts in the PBL process that may undermine some of the intended goals of PBL Since the publication of Physicians for the Twenty-First Century —‘‘the GPEP Report ’ ’ of 1984 , medical educators have identified the need for physicians to become lifelong learners . Part of the impetus for this conclusion arises from several studies that have demonstrated that knowledge and /or competence of physicians decline as a function of time since graduation ; the evidence indicates the cause to be failure to acquire new knowledge rather than a tendency to forget previously learned material . Thus , physicians need to be trained to identify the relevant medical literature ( i.e. , information-seeking skills ) and to apply ‘ ‘ critical appraisal ’’ techniques to analyze potentially useful articles culled from the literature search . There is little published evidence that educational interventions around critical appraisal teaching in undergraduate or postgraduate medical curricula impact in a sustained way the knowledge of epidemiologic principles or the critical application of current research information for clinical decision making . In considering the impact on conceptual knowledge , one could argue that there is a lack of vali date d tools available for evaluating critical appraisal skills ; alternatively , the format of instruction , timing in the curriculum , and duration of instruction may be at fault . More important , studies have not addressed the issue of whether the demonstration of mastery of particular critical appraisal skills can be related to clinical decision making . Ultimately , such mastery becomes largely irrelevant if it does not translate into better judgment . The authors of this study were concerned that , despite the inclusion in the first-year undergraduate curriculum of several focused objectives surrounding critical appraisal in the domain of clinical epidemiology , feedback from clinical faculty suggested that students had only rudimentary knowledge of the application of these principles at the end of the first year . In contrast to this feedback , problem-based learning ( PBL ) is believed to hold the potential to equip graduates with the skills to learn after graduation . In fact , several studies have shown significant differences between students of PBL and students of conventional curricula in the use of recently published medical literature . With this inconsistency in mind , two experimental questions were asked |
12,976 | 24,874,470 | We found no direct evidence that opioids affected patient consciousness , appetite or thirst when used to treat cancer pain .
However , somnolence , dry mouth , and anorexia were common adverse events in people with cancer pain treated with morphine , fentanyl , oxycodone , or codeine . | BACKGROUND There is increasing focus on providing high quality care for people at the end of life , irrespective of disease or cause , and in all setting s. In the last ten years the use of care pathways to aid those treating patients at the end of life has become common worldwide .
The use of the Liverpool Care Pathway in the UK has been criticised .
In Engl and the LCP was the subject of an independent review , commissioned by a Health Minister .
It also found that the LCP often was not implemented properly , and had instead become a barrier to good care ; it made over 40 recommendations , including education and training , research and development , access to specialist palliative care services , and the need to ensure care and compassion for all dying patients .
In July 2013 , the Department of Health released a statement that stated the use of the LCP should be " phased out over the next 6 - 12 months and replaced with an individual approach to end of life care for each patient".The impact of opioids was a particular concern because of their potential influence on consciousness , appetite and thirst in people near the end of life .
There was concern that impaired patient consciousness may lead to an earlier death , and that effects of opioids on appetite and thirst may result in unnecessary suffering .
This rapid review , commissioned by the National Institute for Health Research , used st and ard Cochrane methodology to examine adverse effects of morphine , fentanyl , oxycodone , and codeine in cancer pain studies as a close approximation to possible effects in the dying patient .
OBJECTIVES To determine the impact of opioid treatment on patient consciousness , appetite and thirst in r and omised controlled trials of morphine , fentanyl , oxycodone or codeine for treating cancer pain . | Codeine is widely used in combination with acetaminophen and aspirin for the management of mild to moderate pain . However , there are few controlled clinical trials of single-entity codeine in chronic cancer pain . The purpose of this study was to evaluate the clinical efficacy and safety of controlled-release codeine given every 12 hr in patients with cancer pain . Thirty-five patients with chronic cancer pain were r and omized in a double-blind crossover study to controlled-release ( CR ) codeine or placebo , for 7 days each . Pain intensity was assessed at 0800 hr and 2000 hr using a visual analogue scale ( VAS ) and a five-point categorical scale , and the use of " rescue " acetaminophen-plus-codeine ( 300 mg/30 mg every 4 hr as needed ) was recorded . Thirty patients completed the study ( 17 male , 13 female ; mean age , 64.4 + /- 9.8 years ) with a mean daily CR codeine dose of 277 + /- 77 mg ( range , 200 - 400 mg ) . CR codeine treatment result ed in significantly lower overall VAS pain intensity scores ( 22 + /- 18 mm versus 36 + /- 20 mm , P = 0.0001 ) , categorical pain intensity scores ( 1.2 + /- 0.8 versus 1.8 + /- 0.8 , P = 0.0001 ) , and pain scores when assessed by day of treatment and by time of day . Daily " rescue " analgesic consumption was significantly lower on CR codeine , compared to placebo treatment ( 2.2 + /- 2.3 versus 4.6 + /- 2.8 tablets per day , P = 0.0001 ) . Both patients and investigators preferred CR codeine to placebo ( 80 % versus 3 % , P = 0.0014 and 73 % versus 7 % , P = 0.0160 , respectively ) . These data indicate that CR codeine , given every 12 hr results in significant reductions in pain intensity and the use of " rescue " acetaminophen-plus-codeine in patients with cancer pain . CR codeine provides the benefits of a flexible single entity codeine formulation and the convenience of 12-hr duration of action , which allows patients uninterrupted sleep and improved compliance To compare the effectiveness and safety of controlled-release ( CR ) oxycodone tablets with immediate-release ( IR ) oxycodone in patients with chronic cancer pain , a multicenter , r and omized , double-blind , parallel-group study was performed in 111 patients with cancer pain . Patients were treated with 6 to 12 tablets or capsules of fixed-combination opioid/nonopioid analgesics per day at study entry . Patients received 30 mg of CR oxycodone tablets every 12 hr or 15 mg of IR oxycodone four times daily for 5 days . No titration or supplemental analgesic medications were permitted . The mean ( + /- SE ) baseline pain intensity ( 0 = none , 1 = slight , 2 = moderate , 3 = severe ) was 1.5 + /- 0.1 for the CR oxycodone-treated group and 1.3 + /- 0.1 for the group given IR oxycodone ( P > 0.05 ) . The 5-day mean pain intensity was 1.4 + /- 0.1 and 1.1 + /- 0.1 for the CR and IR groups , respectively ( P > 0.05 ) . Discontinuation rates were equivalent ( 33 % ) . There was no significant difference between treatment groups in the incidence of adverse events . This study demonstrates that cancer pain patients given 6 to 12 tablets or capsules of fixed-dose combination analgesics can be equally well treated with CR oxycodone administered every 12 hr or IR oxycodone four times daily at the same total daily dose . CR oxycodone offers the benefits of twice daily dosing Summary Sustained-release morphine ( MST ) given by the rectal route was compared with oral MST in an open r and omised cross-over trial in ten patients with cancer who received stable doses of MST . No significant difference was found in the areas under the curve of the concentration-time profiles ( AUC ) following oral or rectal administration for parent morphine . The AUCs determine for morphine-6-glucuronide ( M6 G ) and morphine-3-glucuronide ( M3 G ) after oral administration were approximately twice those obtained following rectal administration . The maximal concentration achieved was lower and the time to maximal concentration was longer following rectal administration for morphine , M6 G and M3 G . The relative mean arrival times following rectal administration were significantly longer for morphine and M3 G but not for M6 G . These findings suggest slower absorption but less first-pass metabolism of MST after rectal administration . No significant difference was noted between the oral and the rectal route in measurements on visual-analogue scales for pain or side effects . We recommend the rectal route as being suitable for MST administration when the oral route is no longer available . In changing from oral to rectal administration , the same dose and dose interval may be used , but dose adjustment may be needed & NA ; A controlled trial of diamorphine ( diacetylmorphine , heroin ) and morphine is reported in which the two drugs were administered regularly by mouth in individually determined effective analgesic doses . Elixirs contained cocaine hydrochloride 10 mg/dose ; other drugs were prescribed when indicated clinical ly . 699 patients entered the trial and , of these , 146 crossed from diamorphine to morphine , or vice versa , after about two weeks using an oral potency ratio of 1.5/1 determined in a pilot trial . Additional medication and survival were closely similar in both treatment groups . In the female crossover patients , no difference was noted in relation either to pain or the other symptoms evaluated . On the other h and , male crossover patients experienced more pain , and were more depressed , while receiving diamorphine . In these , the potency ratio of diamorphine to morphine appeared to be less than 1.5/1 . If this is allowed for , then the difference in mood is probably not significant . Compared with male patients , fewer females required a dose of 10 mg or more , but more were prescribed an anxiolytic . The ability to do without a 2 a.m. dose appeared to be related more to the size of the dose than to gender or treatment . It is concluded that , provided allowance is made for the difference in potency , morphine is a satisfactory substitute for orally administered diamorphine . However , when injections are necessary , the greater solubility of its hydrochloride gives diamorphine an important practical advantage over morphine , especially when large doses are required Immediate‐release oral morphine , given every four hours in individually titrated doses , is effective in the control of severe cancer pain . To evaluate the analgesic efficacy of a controlled‐release morphine sulfate preparation , MS Contin tablets ( MSC , Purdue Frederick , Toronto , Ontario , Canada ) , after a single dose and under steady‐state conditions , the authors compared MSC administered every 12 hours with morphine oral solution ( MOS ) administered every 4 hours in 17 adult cancer patients with chronic severe pain . In the single‐dose evaluation , in which the patients were r and omly assigned to receive MSC or MOS , there were no significant differences in analgesic efficacy or requirement for supplemental morphine between the two treatments . With both preparations , pain severity ratings increased toward the end of the 12‐hour , single‐dose observation period and were higher than the pain scores reported after dose titration . In the steady‐state evaluation , which was a r and omized crossover comparison , both preparations provided effective pain control with minimal side effects . There was no significant difference between MSC and MOS in overall pain scores or La pain scores analyzed by time of day and day of therapy . In conclusion , that an individualized twice‐daily regimen of MSC is as effective as 4‐hourly MOS for the control of chronic severe cancer pain . The twice‐daily regimen has several advantages : it allows an uninterrupted night ' sleep , it is substantially more convenient , and it can be expected to reduce both medication errors and noncompliance & NA ; Oral transmucosal fentanyl citrate ( OTFC ® ; Actiq ® ) is a drug delivery formulation used for management of breakthrough cancer pain . Previous studies with open‐label comparisons indicated OTFC was more effective than patients ’ usual opioid for breakthrough pain . The objective of this study was to compare OTFC and morphine sulfate immediate release ( MSIR ® ) for management of breakthrough pain in patients receiving a fixed scheduled opioid regimen . This double‐blind , double‐dummy , r and omized , multiple crossover study was conducted at 19 US university‐ and community‐based hospitals and clinics and comprised 134 adult ambulatory cancer patients . Patients were receiving a fixed scheduled opioid regimen equivalent to 60–1000 mg/day oral morphine or 50–300 & mgr;g/h transdermal fentanyl , were using a ‘ successful ’ MSIR dose ( 15–60 mg ) as defined by entry criteria , and were experiencing 1–4 episodes of breakthrough pain per day . In open‐label fashion , OTFC was titrated such that a single unit ( 200–1600 & mgr;g ) provided adequate pain relief with acceptable side effects . Successfully titrated patients entered the double‐blind phase of the study and received ten prenumbered sets of r and omized capsules and oral transmucosal units . Five sets were the successful OTFC dose paired with placebo capsules , and five sets were placebo OTFC paired with capsules containing the successful MSIR dose . Patients took one set of study medication for each episode of target breakthrough pain . Pain intensity ( PI ) , pain relief ( PR ) and global performance of medication ( GP ) scores were recorded . Pain intensity differences ( PID ) were calculated and 15‐min PID was the primary efficacy variable . Adverse events were recorded . Sixty‐nine percent of patients ( 93/134 ) found a successful dose of OTFC . OTFC yielded outcomes ( PI , PID , and PR ) at all time points that were significantly better than MSIR . GP also favored OTFC and more patients opted to continue with OTFC than MSIR following the study . Somnolence , nausea , constipation , and dizziness were the most common drug‐associated side effects . In conclusion , OTFC was more effective than MSIR in treating breakthrough cancer pain 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 Although the oral route is the preferred method of opioid therapy in patients with cancer pain , many patients will require an alternate route of analgesic administration at some point during the trajectory of their illness . This study compared the efficacy and safety of a novel , controlled-release suppository of morphine ( MSC-R ) and controlled-release morphine tablets ( MSC-T ) in patients with cancer pain . In a double-blind crossover study , 27 patients with cancer pain were r and omized to receive MSC-R or MSC-T every 12 hours for 7 days each , using a 1:1 analgesic equivalence ratio . Pain intensity was assessed using a visual analog scale ( VAS ) and the Present Pain Intensity Index of the McGill Pain Question naire . Nausea and sedation were also assessed with a VAS . Pharmacodynamic assessment s were made by the patient at 8:00 AM , 12:00 PM , 4:00 PM , and 8:00 PM and rescue morphine use recorded in a daily diary . There were no significant differences between MSC-R and MSC-T in overall scores for pain intensity VAS , ordinal pain intensity , and sedation . There was a small but significant difference in overall nausea VAS score in favor of MSC-R. Mean daily rescue analgesic use did not differ significantly during between treatment with MSC-R and MSC-T. MSC-R provides pain control comparable to that provided by MSC-T when given every 12 hours at a 1:1 dose ratio , and represents a reliable alternative method of pain control for patients unable to take oral opioid agents A new 72-hour transdermal fentanyl matrix patch has been design ed , which has a 35%-50 % reduction of the absolute fentanyl content compared with other currently available transdermal fentanyl patches that are using the matrix technology . The new patch has previously been shown to be pharmacokinetically bioequivalent to the marketed fentanyl patch . To determine noninferiority in efficacy in cancer patients and to compare safety , a clinical trial comparing the new fentanyl patch with st and ard oral or transdermal opioid treatment was planned . The design was an open , parallel group , multicenter trial , in which 220 patients were r and omized to receive either the fentanyl patch or st and ard opioid treatment for 30 days . The primary efficacy variable , pain intensity ( PI ) on a 0 - 10-point numerical rating scale , was recorded once daily . The primary endpoint was the relative area under the curve of PI expressed as a percentage of the maximum possible PI area under the curve . Any adverse events were recorded ; four tolerability endpoints , constipation , nausea , daytime drowsiness , and sleeping disturbances , were assessed daily . Noninferiority was shown ; the upper 95 % confidence interval limits of the mean difference in relative PI area under the curve between the fentanyl patch and st and ard opioid treatment were less than 10 % for both the intention-to-treat and per- protocol population s. Scores for the tolerability endpoints were similar in the treatment groups . The new fentanyl matrix patch with a lower drug load was found noninferior and as safe as established st and ard oral and transdermal opioid treatment The antinociceptive effect of morphine and oxycodone is mediated preferentially at μ and κ receptors , respectively . The aim of this study was to evaluate the analgesic profile of the combination of morphine and oxycodone in cancer pain , compared to the st and ard administration of morphine alone . Controlled-release formulations of oxycodone ( CRO ) and morphine ( CRM ) were compared in 26 patients . The study started with an open-label , r and omised titration phase to achieve stable pain control for 7 days , followed by a double-blind , r and omised crossover phase in two periods , 14 days each . At any point , patients were allowed to use oral immediate-release morphine ( IRM ) as needed , in order to keep visual analogue scale ⩽4 . Pain , satisfaction , adverse effects and number of daily rescue morphine tablets were assessed . A total of 22 patients were evaluated . The weekly upload consumption ratio in morphine/oxycodone was 1 : 1.8 ( 1.80 , 1.83 , 1.76 , 1.84 ) . The weekly IRM consumption was higher in patients having CRM compared to patients having CRO ( ratio morphine/oxycodone : 1.6 , 1.6 , 1.6 , 1.7 ) ( P<0.05 ) . Patients receiving oxycodone complained of less nausea and vomiting . The rescue morphine analgesic consumption was 38 % higher in patients receiving only morphine , compared to patients receiving both morphine and oxycodone . The results suggest that the combination of morphine/oxycodone ( opioids with differential preferential sites of action ) can be a useful alternative to morphine alone , result ing in a better analgesia profile and less emesis In a controlled double blind study of analgesics for the pain of gastrointestinal cancer , aspirin ( 650 mg ) was significantly more effective than placebo and superior to orally used codeine sulfate ( 60 mg ) . The effectiveness of aspirin was not specific for carcinoma of the pancreas , however , because the same pattern of pain relief was found in colonic carcinoma The administration of single oral doses of delta‐9‐tetrahydrocannabinol ( THC ) to patients with cancer pain demonstrated a mild analgesic effect . At a dose of 20 mg , however , THC induced side effects that would prohibit its therapeutic use including somnolence , dizziness , ataxia , and blurred vision . Alarming adverse reactions were also observed at this dose . THC , 10 mg , was well tolerated and , despite its sedative effect , may have analgesic potential Oxycodone is an opioid analgesic that closely resembles morphine . Oxymorphone , the active metabolite of oxycodone , is formed in a reaction catalyzed by CYP2D6 , which is under polymorphic genetic control . The role of oxymorphone in the analgesic effect of oxycodone is not yet clear . In this study , controlled-release ( CR ) oxycodone and morphine were examined in cancer pain . CR oxycodone and morphine were administered to 45 adult patients with stable pain for 3 - 6 days after open-label titration in a r and omized , double-blind , cross-over trial . Twenty patients were evaluable . Both opioids provided adequate analgesia . The variation in plasma morphine concentrations was higher than that of oxycodone , consistent with the lower bioavailability of morphine . Liver dysfunction affected selectively either oxycodone or morphine metabolism . Three patients with markedly aberrant plasma opioid concentrations are presented . Significant individual variation in morphine and oxycodone metabolism may account for abnormal responses during treatment of chronic cancer pain The purpose of this double-blind crossover study was to determine whether a sustained-release morphine sulfate ( SRMS ) tablet given orally every 12 hours could adequately replace immediate-release morphine sulfate solution ( IRMS ) given orally every 4 hours in hospitalized patients with chronic pain from advanced cancer . Of 33 patients entered , 27 completed the study and were included in the efficacy and safety analysis . Patients were initially r and omized to receive either 30-mg SRMS tablets every 12 hours or IRMS at the same mg/24 hours dose , every 4 hours . After 2 days , a crossover was performed , and patients received the alternate treatment for 3 days . Pain and side effects were assessed using a st and ard 100 mm visual analogue scale ( VAS ) . There were no statistically significant differences between the two treatment groups for mean VAS pain scores or scores for sleepiness , nausea , depression , and anxiety . The incidence of breakthrough pain was similar for both treatment groups , as was the incidence of confusion and constipation . The results demonstrated that SRMS is a safe , effective analgesic preparation for patients who require oral opioids for cancer pain . The data also support the conclusion that sustained-release morphine tablets administered every 12 hours can replace an immediate-release morphine solution administered every 4 hours The European Association for Palliative Care guidelines for treatment of cancer pain recommend a double dose ( DD ) of immediate-release morphine at bedtime instead of single doses ( SD ) repeated every four hours throughout the night . A previous open controlled study reported more side effects after DD than after SD . The present study was a r and omized , double-blind , crossover study comparison of DD and SD of immediate-release morphine during the night , followed by an open pharmacokinetic study . The primary outcome was average pain intensity during the night , as measured on an 11-point numerical rating scale . Secondary outcomes were morning pain , number of rescue medications , adverse effects ( nausea , xerostomia , tiredness , sleep quality , and number of awaking episodes ) and patient preference . Morphine and metabolites were quantified by a vali date d liquid chromatography-t and em mass spectrometry method . Nineteen patients completed the clinical study ; 13 participated in the pharmacokinetic follow up . Average pain during the night for DD vs. SD was close to statistical significance ( mean 0.8 and 1.4 , respectively , P=0.058 ; mean [ 95 % confidence interval ] for the difference was 0.50 [ 0.02 , 1.0 ] ) . A similar trend was observed for strongest night pain ( P=0.069 ) and sleep quality ( P=0.077 ) . Only two patients required rescue morphine . Four patients had no treatment preference ; nine and six favored DD and SD , respectively . DD patients displayed higher area under the curve for morphine and morphine-6-glucuronide during the first part of the night . Although DD tended to perform slightly better than SD , a difference in average pain during the night of 0.50 has little clinical significance , and the two procedures are , therefore , clinical ly equivalent . It is speculated whether the initial higher exposure to morphine-6-glucuronide may have clinical significance The MS Contin tablet 200 mg ( controlled release morphine sulphate ) provides an equivalent rate and extent of absorption to two MS Contin tablets 100 mg . The characteristics of controlled release from this higher strength formulation are also consistent with those of the 100 mg tablet . The level of analgesia provided during the early post-dosing period , at the end of the dosing period and overall over the twelve hour interval were also equivalent between the preparations . The addition of the MS Contin tablet 200 mg to the existing range will facilitate oral dosing in patients requiring large doses of morphine . This extension to the range will increase the choice available to the clinician and provide a natural progression for those patients requiring a step-up in the dose titration procedure As professionals , we want to use the best treatments ; as patients , we want to be given them . Knowing whether an intervention works ( or does not work ) is fundamental to clinical decision making . However , clinical decision making involves more than simply taking published results of research directly to the bedside . Physicians need to consider how similar their patients are to those in the published studies , to take the values and preferences of their patients into account , and to consider their own experience with a given test or treatment . Evidence from clinical research is becoming increasingly important in medical- practice decisions as more and better evidence is published . But when is the evidence strong enough to justify changing a practice ? Individual studies that involve only small numbers of patients may have results that are distorted by the r and om play of chance and thus lead to less than optimal decisions . As is clear from other papers in this series , systematic review s identify , critically appraise , and review all the relevant studies on a clinical question and are more likely to give a valid answer . They use explicit methods and quality st and ards to reduce bias . Their results are the closest we can come to reaching the truth given our current state of knowledge . The questions about an intervention that a systematic review should answer are the following : 1 . Does it work ? 2 . If it works , how well does it work in general and compared with placebo , no treatment , or other interventions that are currently in use ? 3 . Is it safe ? 4 . Will it be safe and effective for my patients ? Whereas the critical appraisal and qualitative synthesis provided by review articles can be interpreted directly , the numerical products of quantitative review s can be more difficult to underst and and apply in daily clinical practice . This paper provides guidance on how to interpret the numerical and statistical results of systematic review s , translate these results into more underst and able terms , and apply them directly to individual patients . Many of these principles can also be used to interpret the numerical results of individual clinical studies . They are particularly relevant to systematic review s , however , because such review s contain more information than do primary studies and often exert greater influence than do individual studies . Making Sense of the Numerical Results of Clinical Studies Although the results of clinical studies can be expressed in intuitively meaningful ways , such results do not always easily translate into clinical decision making . For example , results are frequently expressed in terms of risk , which is an expression of the frequency of a given outcome . ( Risks are probabilities , which can vary between 0.0 and 1.0 . A probability of 0.0 means that the event will never happen , and a probability of 1.0 means that it always happens . ) Consider a hypothetical study of the recurrence of migraine headaches in a control group receiving placebo and a treatment group receiving a new antimigraine preparation , drug M ( a secondary prevention trial ) . Suppose that at the end of the trial , migraines recurred in 30 % of the control group ( the risk for recurrence was 0.30 ) but in only 5 % of the drug M group ( risk of 0.05 ) ( Table 1 ) . Table 1 . Numerical Expression of Hypothetical Clinical Trial Results The outcomes of the study are clear enough for the two groups when they are examined separately . But clinicians and patients are more interested in the comparative results , that is , the outcome in one group relative to the outcome in the other group . This overall ( comparative ) result can be expressed in various ways . For example , the relative risk , which is the risk in the treatment group relative to that in the control group , is simply the ratio of the risks in the two groups . In other words , relative risk is the risk in the treatment group divided by that in the control group , 0.05 0.30 , or 0.17 . The comparison can also be expressed as the reduction in relative risk , which is the ratio between the decrease in risk ( in the treatment group ) and the risk in the control group , 0.25 0.30 , or 0.83 ( Table 1 ) . ( The relative risk reduction can also be calculated as 1 relative risk ) . Although the clinical meaning of relative risk ( and relative risk reduction ) is reasonably clear , relative risk has the distinct disadvantage that a given value ( for example , 0.17 ) is the same whether the risk with treatment decreases from 0.80 to 0.14 , from 0.30 to 0.05 , from 0.001 to 0.00017 , and so forth . The clinical implication s of these changes clearly differ from one another enormously and depend on the specific disease and intervention . An important alternate expression of comparative results , therefore , is the absolute risk reduction . Absolute risk reduction is determined by subtracting the risk in one group from the risk in the other ( for example , the risk in the treatment group is subtracted from the risk in the placebo group ) . In the case of our migraine study , the absolute risk reduction would be 0.30 0.05 , which equals 0.25 , or 25 percentage points . In contrast , for a study in which the risk decreased from 0.001 to 0.00017 , the absolute risk reduction would be only 0.00083 , or 0.083 percentage points , which is a trivial change in comparison ( Table 1 ) . This arithmetic emphasizes the difficulty of expressing the results of clinical studies in meaningful ways . Relative risk and relative risk reduction clearly give a quantitative sense of the effects of an intervention in proportional terms but provide no clue about the size of an effect on an absolute scale . In contrast , although it tells less about proportional effects , absolute risk says a great deal about whether an effect is likely to be clinical ly meaningful . Despite this benefit , even absolute risk is problematic because it is a dimensionless , abstract number ; that is , it lacks a direct connection with the clinical situation in which the patient and physician exist . However , another way of expressing clinical research results can provide that clinical link : the number needed to treat ( NNT ) . Number Needed To Treat The NNT for a given therapy is simply the reciprocal of the absolute risk reduction for that treatment [ 1 , 2 ] . In the case of our hypothetical migraine study ( in which risk decreased from 0.30 without treatment with drug M to 0.05 with treatment with drug M , for a relative risk of 0.17 , a relative risk reduction of 0.83 , and an absolute risk reduction of 0.25 ) , the NNT would be 1 0.25 , or 4 . In concrete clinical terms , an NNT of 4 means that you would need to treat four patients with drug M to prevent migraine from recurring in one patient . To emphasize the difference between the concepts embodied in NNT and relative risk , recall the various situations mentioned above , in all of which the relative risk was 0.17 but in which the absolute risk decreased from 0.80 to 0.14 in one case and from 0.001 to 0.00017 in another . Note that the corresponding NNTs in these two other cases are 1.5 and 1204 , respectively : that is , you would need to treat 1.5 and 1204 patients to obtain a therapeutic result in these two situations compared with 4 patients with drug M ( Table 1 ) . The NNT can be calculated easily and kept as a single numerical reminder of the effectiveness ( or , as we will see , the potential for harm ) of a particular therapy . As we suggested , the NNT has the crucial advantage of direct applicability to clinical practice because it shows the effort that is required to achieve a particular therapeutic target . The NNT has the additional advantage that it can be applied to any beneficial outcome or any adverse event ( when it becomes the number needed to harm [ NNH ] ) . The concept of NNT always refers to a comparison group ( in which patients receive placebo , no treatment , or some other treatment ) , a particular treatment outcome , and a defined period of treatment . In other words , the NNT is the number of patients that you will need to treat with drug or treatment A to achieve an improvement in outcome compared with drug or treatment B for a treatment period of C weeks ( or other unit of time ) . To be fully specified , NNT and NNH must always specify the comparator , the therapeutic outcome , and the duration of treatment that is necessary to achieve the outcome . Important Qualities of the Number Needed To Treat The NNT is treatment specific . It describes the difference between treatment and control in achieving a particular clinical outcome . Table 2 shows NNTs from a selection of systematic review s and large r and omized , controlled trials . Table 2 . Numbers Needed To Treat from Systematic Review s and R and omized , Controlled Trials A very small NNT ( that is , one that approaches 1 ) means that a favorable outcome occurs in nearly every patient who receives the treatment and in few patients in a comparison group . Although NNTs close to 1 are theoretically possible , they are almost never found in practice . However , small NNTs do occur in some therapeutic trials , such as those comparing antibiotics with placebo in the eradication of Helicobacter pylori infection or those examining the use of insecticide for head lice ( Table 2 ) . An NNT of 2 or 3 indicates that a treatment is quite effective . In contrast , such prophylactic interventions as adding aspirin to streptokinase to reduce 5-week vascular mortality rates after myocardial infa rct ion may have NNTs as high as 20 to 40 and still be considered clinical ly effective . Limitations of the Number Needed To Treat Although NNTs are powerful instruments for interpreting clinical effects , they also have important limitations . First , an NNT is generally expressed as a single number , which is known as its point estimate . As with all experimental measurements , however , the true value of the NNT can be higher or lower than the point estimate determined through clinical studies . The 95 % CIs of the NNT are useful in this regard because they provide an indication that CONTEXT R and omized trials with adequate sample size offer an opportunity to assess the safety of new medications in a controlled setting ; however , generalizable data on drug safety reporting are sparse . OBJECTIVE To scrutinize the completeness of safety reporting in r and omized trials . DESIGN , SETTING , AND PATIENTS Survey of safety reporting in 192 r and omized drug trials 7 diverse topics with sample sizes of at least 100 patients and at least 50 patients in a study arm ( N = 130074 patients ) . Trial reports were identified from comprehensive meta-analyses in 7 medical areas . MAIN OUTCOME MEASURES Adequate reporting of specific adverse effects and frequency and reasons for withdrawals due to toxic effects ; article space allocated to safety reporting and predictors of such reporting . RESULTS Severity of clinical adverse effects and laboratory-determined toxicity was adequately defined in only 39 % and 29 % of trial reports , respectively . Only 46 % of trials stated the frequency of specific reasons for discontinuation of study treatment due to toxicity . For these 3 parameters , there was significant heterogeneity in rates of adequate reporting across topics ( P = .003 , P<.001 , and P = .02 , respectively ) . Overall , the median space allocated to safety results was 0.3 page . A similar amount of space was devoted to contributor names and affiliations ( P = .16 ) . On average , the percentage of space devoted to safety in the results section was 9.3 % larger in trials involving dose comparisons than in those that did not ( P<.001 ) and 3.8 % smaller in trials reporting statistically significant results for efficacy outcomes ( P = .047 ) . CONCLUSIONS The quality and quantity of safety reporting vary across medical areas , study design s , and setting s but they are largely inadequate . Current st and ards for safety reporting in r and omized trials should be revised to address this inadequacy Objective : An examination of whether oxycodone/naloxone prolonged-release tablets ( OXN PR ) can improve constipation and maintain analgesia , compared with oxycodone prolonged-release tablets ( OxyPR ) in patients with moderate/severe cancer pain . Methods : R and omized , double-blind , active-controlled , double-dummy , parallel-group study in which 185 patients were r and omized to receive up to 120 mg/day of OXN PR or OxyPR over 4 weeks . Efficacy assessment s included Bowel Function Index ( BFI ) , Brief Pain Inventory Short-Form ( BPI-SF ) , laxative and rescue medication use . Quality of life ( QoL ) and safety assessment s were conducted . Results : After 4 weeks , mean BFI score was significantly lower with OXN PR ; mean total laxative intake was 20 % lower with OXN PR . Mean BPI-SF scores were similar for both treatments and the average rate of analgesic rescue medication use was low and comparable . QoL assessment s were stable and comparable with greater improvements in constipation-specific QoL assessment s with OXN PR . Overall , rates of adverse drug reactions were similar . Conclusions : OXN PR provides superior bowel function in cancer pain patients , compared with OxyPR , without compromising analgesic efficacy or safety . This study confirms that OXN PR is well tolerated and efficacious in cancer pain patients and results are in line with those seen in non-malignant pain patients Background Long-acting opioid formulations are advocated for maintaining pain control in chronic cancer pain . OROS ® hydromorphone is a sustained-release formulation of hydromorphone that requires dosing once daily to maintain therapeutic concentrations . The objective of this study was to demonstrate the clinical equivalence of immediate-release and sustained-release formulations of hydromorphone and morphine for chronic cancer pain . Methods 200 patients with cancer pain ( requiring ≤ 540 mg/d of oral morphine ) participated in this double-blind , parallel-group trial . Patients were r and omized to receive hydromorphone or morphine ( immediate-release for 2–9 days , sustained-release for 10–15 days ) . Efficacy was assessed with the Brief Pain Inventory ( BPI ) , investigator and patient global evaluations , Eastern Cooperative Oncology Group performance status , and the Mini-Mental State Examination . The primary endpoint was the ' worst pain in the past 24 hours ' item of the BPI , in both the immediate-release and sustained-release study phases , with treatments deemed equivalent if the 95 % confidence intervals ( CI ) of the between-group differences at endpoint were between -1.5 and 1.5 . No equivalence limits were defined for secondary endpoints . Results Least-squares mean differences ( 95 % CI ) between groups were 0.2 ( -0.4 , 0.9 ) in the immediate-release phase and -0.8 ( -1.6 , -0.01 ) in the sustained-release phase ( intent-to-treat population ) , indicating that the immediate-release formulations met the pre-specified equivalence criteria , but that the lower limit of the 95 % CI ( -1.6 ) was outside the boundary ( -1.5 ) for the sustained-release formulations . BPI ' pain now PM ' was significantly lower with OROS ® hydromorphone compared with controlled-release morphine ( least-squares mean difference [ 95 % CI ] , -0.77 [ -1.49 , -0.05 ] ; p = 0.0372 ) . Scores for other secondary efficacy variables were similar between the two sustained-release treatments . At endpoint , > 70 % of investigators and patients rated both treatments as good to excellent . The safety profiles of hydromorphone and morphine were similar and typical of opioid analgesics . Conclusion Equivalence was demonstrated for immediate-release formulations of hydromorphone and morphine , but not for the sustained-release formulations of OROS ® hydromorphone and controlled-release morphine . The direction of the mean difference between the treatments ( -0.8 ) and the out-of-range lower limit of the 95 % CI ( -1.6 ) were in favor of OROS ® hydromorphone . Trial registration Clinical Trials.gov : Reporting harms may cause more trouble and discredit than the fame and glory associated with successful reporting of benefits ( 1 ) . The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement , a checklist ( Table 1 ) flow diagram first published in 1996 and revised 5 years later ( 2 , 3 ) , is an effort to st and ardize , and thereby improve , published reports of r and omized , controlled trials ( RCTs ) . One of the additions to the 2001 revision was an item about reporting adverse events . This single item did not do full justice to the importance of harms-related issues . The CONSORT Group met in September 2001 to discuss how to correct this deficiency . We aim ed to provide evidence -based guidance on the reporting of harms in RCTs . First , we search ed MEDLINE , EMBASE , Web of Science , and the Cochrane Library using a wide array of terms related to harms and identified pertinent evidence . We also communicated with experts and review ed bibliographies of identified articles to find additional studies . At a meeting in Montebello , Quebec , Canada , in May 2003 , CONSORT Group members , including several journal editors and additional experts in related fields , held a structured discussion of recommendations about reporting of harms-related issues in RCTs . The discussion s led to a written document that we circulated among the team members for comment . The present manuscript describes our recommendations on the appropriate reporting of harms in RCTs . Table 1 . Original CONSORT Checklist The terminology of harms-related issues in RCTs is confusing and often misleading or misused ( see Glossary ) ( 4 , 5 ) . Safety is a reassuring term that may obscure the real and potentially major harms that drugs and other interventions may cause . We encourage authors to use the term harms instead of safety . In addition to misused terminology , reporting of harms in RCTs has received less attention than reporting of efficacy and effectiveness and is often inadequate ( 6 - 14 ) . In short , both scientific evidence and ethical necessity call for action to improve the quality of reporting of harms in RCTs ( 15 , 16 ) . Here , we present a set of recommendations and accompanying explanations for the proper reporting of harms in RCTs . These recommendations should complement the existing CONSORT statement ( Table 2 ) . Examples are presented on the Annals and CONSORT ( www.consort-statement.org ) Web sites . Table 2 . Checklist of Items To Include When Reporting Harms in R and omized , Controlled Trials Recommendations Title and Abstract Recommendation 1 . If the study collected data on harms and benefits , the title or abstract should so state . The title should mention harms if the study of harms was a key trial objective . Many phase I and phase II trials , some phase II/III trials , and most phase IV trials ( 17 , 18 ) target harms as primary outcomes . Yet , the title and abstract seldom contain the word harm . Among 375143 entries in the Cochrane Central Register of Controlled Trials ( Cochrane Library , issue 3 , 2003 ) , search ing titles with the search terms harm or harms yielded 337 references ( compared with 55374 for efficacy and 23415 for safety ) . Of the 337 , excluding several irrelevant articles on self-harm or harm reduction , only 3 trial reports and 2 abstract s contained the word harm in their titles . Authors should present information on harms in the abstract . If no important harms occurred , authors should so state . Explicit reference to the reporting of adverse events in the title or abstract is also important for appropriate data base indexing and information retrieval ( 19 ) . Introduction Background Recommendation 2 . If the trial addresses both harms and benefits , the introduction should so state . The introduction states the scientific background and rationale of an RCT . This requires a balanced presentation whereby the possible benefits of the intervention under investigation are outlined along with the possible harms associated with the treatment . R and omized , controlled trials that focus primarily on harms should clearly state this interest when describing the study objectives in the Introduction and in defining these objectives in the Methods . Methods Outcomes Recommendation 3 . List addressed adverse events with definitions for each ( with attention , when relevant , to grading , expected vs. unexpected events , reference to st and ardized and vali date d definitions , and description of new definitions ) . The Methods section should succinctly define the recorded adverse events ( clinical and laboratory ) . Authors should clarify whether the reported adverse events encompass all the recorded adverse events or a selected sample . They should explain how , why , and who selected adverse events for reporting . In trials that do not mention harms-related data , the Methods section should briefly explain the reason for the omission ( for example , the design did not include the collection of any information on harms ) . Authors should also be explicit about separately reporting anticipated and unexpected adverse events . Expectation may influence the incidence of reported or ascertained adverse events . Making participants aware in the consent form of the possibility of a specific adverse event ( priming ) may increase the reporting rate of the event ( 20 ) . Another example of priming is the finding that the rates of withdrawals due to adverse events and the rates of specific adverse events were significantly higher in trials of aspirin , diclofenac , or indomethacin with comparator drugs compared with placebo-controlled trials ( 21 ) . Presumably , participants were more eager to come forth and report an adverse event or to withdraw from treatment when they knew they could not be receiving inactive placebo . Authors should report whether they used st and ardized and vali date d measurement instruments for adverse events . Several medical fields have developed st and ardized scales ( 22 - 32 ) . Use of nonvali date d scales is common . The source document for well-established definitions and scales should be referenced . New definitions for adverse events should be explicit and clear . Authors should describe how they developed and vali date d new scales . For interventions that target healthy individuals ( for example , many preventive interventions ) , any harm , however minor , may be important to capture and report because the balance of harms and benefits may easily lean toward harms in a low-risk population . For other population s and for interventions that improve major outcomes ( for example , survival ) , severe and life-threatening adverse events may be the only ones that are important in the balance of benefits and harms . Recommendation 4 . Clarify how harms-related information was collected ( mode of data collection , timing , attribution methods , intensity of ascertainment , and harms-related monitoring and stopping rules , if pertinent ) . It is important to describe the question naires , interviews , and tests used to collect information on harms , as well as their timing during follow-up . Passive surveillance of harms leads to fewer recorded adverse events than active surveillance ( 4 ) . Open-ended questions may yield different information , both quantitatively and qualitatively , than structured question naires ( 33 ) . Studies of nonsteroidal , anti-inflammatory drugs ( NSAIDs ) exemplify how data collection methods can affect the detection and reporting of harms . When selective NSAIDs with fewer gastrointestinal adverse events became available , trials reported more than 10 times as many ulcers when comparing these drugs with older NSAIDs as when older NSAIDs were compared with placebo . In the newer trials , more ulcers were detected because participants had regular endoscopy , and the case definition of ulcers was more sensitive ( 34 ) . Authors should specify the time frame of surveillance for adverse events . Some investigators stop recording adverse events at the end of the intervention period or a certain number of days afterward ( for example , 30 days after discontinuation of drug therapy ) and miss events with long latency ( 35 ) . Surgical trials often capture only the adverse events that occur intraoperatively . Several important surgical complications are likely to occur later . Finally , in crossover trials , delayed events might occur while the patient is taking a subsequent assigned treatment . Attribution is the process of deciding whether an adverse event is related to the intervention . Whenever authors filter events through an attribution process , they should state who makes the attribution ( investigators , participants , sponsors , or combinations ) , whether the process is blinded to assigned treatment , and what definitions of adverse events they use ( 4 ) . Discontinuations and withdrawals due to adverse events are especially important because they reflect the ultimate decision of the participant and /or physician to discontinue treatment . Although treatment may occasionally be discontinued for mild or moderate adverse events , attributing discontinuation to a specific reason ( to toxicity , lack of efficacy , other reasons , or combinations of reasons ) may be difficult . For example , in psychopharmacology , dropouts may reflect treatment ineffectiveness as much as toxicity-related intolerance ( 36 ) . Trial reports should specify who gave the reasons for discontinuation ( participants or physicians ) and whether attribution was blinded to the assigned treatment . For example , even in blinded trials , participants and their clinicians are often unblinded before they decide whether to discontinue the intervention . It is important to report participants who are nonadherent or lost to follow-up because their actions may reflect their inability to tolerate the intervention . Moreover , authors should specify how they h and led withdrawals in the analyses of the data . R and omized , controlled trials should report any plan for monitoring for harms and rules for stopping the trial because of harms ( 37 ) . They should clarify whether stopping guidelines examine benefits and harms The single-dose pharmacokinetics and pharmacodynamics of oxycodone administered by the intravenous and rectal routes were determined in 12 adult cancer patients with moderate to severe cancer pain ( visual analog scale [ VAS ] score , approximately 5 ) . Oxycodone was administered by the intravenous and rectal routes with open drug administration and a cross-over design . After single-dose intravenous administration ( 7.9 + /- 1.5 mg , mean + /- SD ) , the mean ( + /- SD ) terminal half-life was 3.4 h ( + /- 1.1 ) , the mean ( + /- SD ) plasma clearance was 45.4 L/h ( + /- 10.1 ) , and the mean ( + /- SD ) volume of distribution in the terminal phase was 3.0 L/kg ( + /- 1.1 ) . After rectal oxycodone ( 30 mg ) , the mean ( + /- SD ) absorption lag time was 0.52 h ( + /- 0.29 ) and the mean ( + /- SD ) absolute bioavailability was 61.6 % ( + /- 30.2 % ) . Intravenous oxycodone was associated with a rapid onset of pain relief ( 5 - 8 min ) in contrast to the 0.5- to 1.0-h delay observed after rectal administration . However , rectal oxycodone provided analgesia of much longer duration ( approximate equals 8 - 12 h ) than did intravenous oxycodone ( approximate equals 4 h ) . There were no significant differences ( P > 0.05 ) in the incidence and severity of side effects between intravenous and rectal oxycodone . The marked interindividual variation observed in the pharmacokinetics and pharmacodynamics of oxycodone in this study emphasizes the need for individualized dosing regimens . ( Anesth Analg 1995;80:296 - 302 We compared the effects of controlled-release and immediate-release morphine preparations in adult patients with moderate-to-severe cancer pain and report method ologic approaches to pain evaluation . The study consisted of a two-phase r and omized crossover trial preceded by a titration phase ; all phases were conducted under double-blind conditions . To evaluate pain intensity , a visual analogue scale ( VAS ) and the Present Pain Intensity scale of the McGill Pain Question naire were used . Additional morphine solution for breakthrough pain was used as an outcome measure . Pain was evaluated nine times daily , which permitted correlation of pain scores with the pharmacokinetic patterns of the test drugs . Side effects were rated once daily , using a scale from 0 to 3 . To assess the relative importance of side effects , a toxicity index was design ed based on both the intensity and duration of each side effect . The overall VAS pain scores during treatment with controlled-release and immediate-release morphine were 1.3 ( SD = 0.1 ) and 1.4 ( SD = 0.2 ) , respectively . Use of supplemental morphine solution for breakthrough pain expressed as the percentage of the daily dose of the test drug was 5.5 % for the controlled-release drug and 10.9 % for the immediate-release drug . Differences in pain scores , side effects , and supplemental morphine requirement between the two groups were not significant . We discuss method ologic issues in double-blind clinical trials of analgesics , in particular the validity of " Patient Preference " as an outcome measure and problems related to the titration phase The efficacy , tolerability and 24-h duration of action of MXL ® capsules , a novel once-daily morphine preparation , were compared with twice-daily morphine tablets ( MST Continus ® tablets ) in patients with severe cancer pain . Eighty-five patients were recruited to this r and omized , double-blind , double-dummy , crossover study . There was no significant difference between the two treatment groups in the number of occasions that escape medication was required , the pain scores at each of three time points throughout the day , and the number of nights woken due to pain . Both preparations were well tolerated with no significant difference in the number or severity of reported symptoms and side-effects . Sixteen patients withdrew from the study , of whom 13 withdrew for nontreatment-related reasons . There was no difference between the preparations in terms of expressed treatment preference . MXL capsules were shown to provide effective analgesia over the 24-h dosing interval which was comparable to that of MST Continus tablets administered twice daily & NA ; A titration procedure using immediate‐release morphine given 4‐hourly is recommended during start of oral morphine for cancer pain . This recommendation is not based on evidence from controlled studies , and many physicians start morphine treatment with controlled‐release morphine . We included 40 patients with malignant disease and pain despite treatment with opioids for mild to moderate pain in a r and omized , double‐blind , double‐dummy , parallel‐group study comparing titration with immediate‐release morphine given 4‐hourly with titration with sustained‐release morphine given once daily . The primary end point was the time needed to achieve adequate pain relief Secondary end points were other symptoms ( nausea , tiredness , lack of sleep , vertigo , appetite and constipation ) , health related quality of life and patient satisfaction . The mean times needed for titration were 2.1 ( 95 % CI ; 1.4–2.7 ) days using immediate‐release morphine and 1.7 ( 95 % CI ; 1.1–2.3 ) days using sustained‐release morphine . Patients titrated with immediate‐release reported statistically significant more tiredness at the end of titration . We observed no other differences in adverse effects or health related quality of life functions between the two treatments . Similar global satisfactions with the morphine treatments were reported . In conclusion , a simplified titration using sustained‐release morphine once daily is equally effective as immediate‐release morphine given 4‐hourly PURPOSE To compare the effectiveness and side effects of methadone and morphine as first-line treatment with opioids for cancer pain . PATIENTS AND METHODS Patients in international palliative care clinics with pain requiring initiation of strong opioids were r and omly assigned to receive methadone ( 7.5 mg orally every 12 hours and 5 mg every 4 hours as needed ) or morphine ( 15 mg sustained release every 12 hours and 5 mg every 4 hours as needed ) . The study duration was 4 weeks . RESULTS A total of 103 patients were r and omly assigned to treatment ( 49 in the methadone group and 54 in the morphine group ) . The groups had similar baseline scores for pain , sedation , nausea , confusion , and constipation . Patients receiving methadone had more opioid-related drop-outs ( 11 of 49 ; 22 % ) than those receiving morphine ( three of 54 ; 6 % ; P = .019 ) . The opioid escalation index at days 14 and 28 was similar between the two groups . More than three fourths of patients in each group reported a 20 % or more reduction in pain intensity by day 8 . The proportion of patients with a 20 % or more improvement in pain at 4 weeks in the methadone group was 0.49 ( 95 % CI , 0.34 to 0.64 ) and was similar in the morphine group ( 0.56 ; 95 % CI , 0.41 to 0.70 ) . The rates of patient-reported global benefit were nearly identical to the pain response rates and did not differ between the treatment groups . CONCLUSION Methadone did not produce superior analgesic efficiency or overall tolerability at 4 weeks compared with morphine as a first-line strong opioid for the treatment of cancer pain This study compared the efficacy and the adverse effects of controlled-release morphine ( CRM ) suspension ( SAR 213 ) and CRM tablets ( Moscontin ) in the treatment of cancer pain . This multicenter , r and omized , double-blind , double-dummy , crossover study was carried out on 52 patients . Each patient received both study treatments given at an equivalent dosage of morphine during each of two 7-day periods . The primary outcome variable was the severity of pain assessed three times daily by means of a visual analogue scale . Secondary criteria of efficacy were the severity of pain assessed by verbal rating scale , the need for " rescue " doses of immediate-release morphine , treatment preference , and indices of quality of life ( activity , mood , sleep ) . There were no statistically significant differences in the parameters assessed when comparing the two groups . This study shows that , when prescribed at the same doses , CRM suspension and CRM tablets have similar efficacy and adverse effects , as well as the same duration of action . The results of this first clinical study carried out on CRM suspension are especially relevant for patients with cancer pain who have difficulty swallowing Recently a sustained-release morphine sulfate tablet ( MS Contin [ MSC ] ) was introduced in Canada . In a r and omized double-blind crossover trial we compared MSC given every 12 hours with a morphine sulfate solution ( MSS ) given every 4 hours to 17 patients suffering from chronic severe pain . After titration of the morphine dosage to optimize the analgesic effect , each patient received 10 days of therapy with either MSC or MSS , then 10 days of therapy with an equal daily dose of the other formulation . Both preparations provided effective pain control , with minimal side effects . There was no significant difference between MSC and MSS in pain scores on a visual analogue scale ( VAS ) , severity scores for tiredness and nausea , amount of supplemental morphine needed for break-through pain or patient preference . The plasma morphine concentrations tended to be greater during treatment with MSC . The study had an 89 % probability of detecting a clinical ly significant difference in VAS pain scores . We conclude that an individualized , twice-daily regimen of MSC is as effective as MSS given every 4 hours for control of severe pain . The twice-daily regimen has several advantages : it provides for an uninterrupted night 's sleep , it is substantially more convenient than the six doses per day required with MSS , and it should help reduce both medication errors and noncompliance In a double-blind , r and omised and parallel clinical trial , two oral doses of dipyrone ( 1 and 2 g ) administered every 8 h were compared with 10 mg of oral morphine given every 4 h for the relief of chronic cancer pain . A total of 121 patients with cancer pain without gastric involvement participated in a 7-day treatment course and were allocated to receive either dipyrone 1 g ( n = 41 ) , dipyrone 2 g ( n = 38 ) or morphine ( n = 42 ) . Drug efficacy was analysed according to the degree of pain relief using a 100-mm visual analogue scale , and the number of patients who decided to increase the dose of the analgesic drug on day 4 . The analgesic effect of dipyrone , 2 g every 8 h , was similar to that of morphine . The efficacy of both schedules was significantly greater than that of dipyrone , 1 g every 8 h. Dipyrone at either 1 or 2 g doses tended to be better tolerated than morphine , although the differences were not statistically significant UNLABELLED Comparison of TD-fentanyl with sustained-release morphine in the pain treatment of patients with lung cancer AIM The aim of this r and omized and controlled trial was to evaluate the analgesic efficacy of trans-dermal fentanyl ( TDF ) and sustained-release oral morphine ( SRM ) primarily and their side effects secondarily , in patients with chronic lung cancer-related pain . MATERIAL - METHODS According to three step analgesic guidelines recommended by the World Health Organization , 50 chronic lung cancer patients requiring third line therapy were enrolled and received either TDF patch ( Grup F , n=25 ) or SRM per orally ( Grup M , n=25 ) for 15 days . Patients were assessed in view to numeric rating scale of their pain , as well as the drugs ' side effects like constipation , nausea-vomiting , urinary retention and urticaria , hypoventilation . RESULTS Pain scores were similar for both groups at the beginning ( p>0.05 ) . While significantly lower pain scores were achieved on the 7th and 15th days compared to those of initial values in Group F and Group M patients ( p<0.001 ) ; these decreases did not reach statistical significance between the groups ( p>0.05 ) . Compared to Group M , constipation was significantly lower in Group F ( 14 patients and 64 % vs. 6 patients and 27 % , respectively ) ( p=0.03 ) . However , the frequencies of nausea-vomiting , urinary retention and urticaria were different between the groups ( p>0.5 ) . None of the patients developed hypoventilation . CONCLUSION Both TDF and SRM are safe and effective analgesics for the management of chronic cancer pain . However , TDF is associated with significantly less constipation rate than that of with SRM Thirty patients with cancer pain completed a double-blind crossover study comparing controlled-release ( CR ) and immediate-release ( IR ) oxycodone . In open-label titration ( 2 to 21 days ) , these patients were stabilized on IR oxycodone qid . They were then r and omized to double-blind treatment with CR oxycodone q12h or IR oxycodone qid for 3 to 7 days followed by crossover at the same daily dose . Mean ( + /- SD ) pain intensity ( 0 = none to 10 = severe ) decreased from a baseline of 6.0 + /- 2.2 to 2.7 + /- 1.1 after titration with IR oxycodone dosed qid . Pain intensity remained stable throughout double-blind treatment : 2.7 + /- 1.9 with CR oxycodone and 2.8 + /- 1.9 with IR oxycodone . Acceptability of therapy and pain scores correlated with plasma oxycodone concentrations for each interval and were similar for both medications ( IR and CR oxycodone ) . Adverse events were similar for both formulations . Following repeat dosing under double-blind conditions , oral CR oxycodone administered q12h provided analgesia comparable to IR oxycodone given qid Ciramadol is a new opioid agonist-antagonist analgesic with low potential for dependency . Forty-three patients with moderate to severe chronic pain from primary or metastatic malignancy of the bone or major organs were enrolled in a r and omized double-blind study that compared orally administered ciramadol ( 30 mg or 90 mg ) to codeine ( 60 mg ) and placebo . A single-dose , four-way crossover design , with a r and omized Latin-square treatment sequence , was used . Data for 40 patients who received the above four study medications were included in the final statistical analysis of efficacy . Analgesic efficacy was measured at 0 , 0.5 , 1.0 , 2.0 , 3.0 , 4.0 , 5.0 , and 6.0 hours , using st and ard visual and verbal pain relief and pain intensity scales . All active therapies provided greater pain relief than placebo ( P less than .05 ) . Ciramadol 30 mg and codeine 60 mg demonstrated equal analgesic activity , whereas ciramadol 90 mg was superior to both therapies . The predominant adverse experiences associated with ciramadol were nausea and drowsiness , which were apparently not dose related . Ciramadol appears to be an effective analgesic at the doses tested , with tolerable gastrointestinal central nervous system side effects at both the 30- and 90-mg dose levels PURPOSE This study was conducted to compare the relative analgesic efficacy and safety of an every-4-hour immediate-release oral morphine ( IRM ) solution with that of an every-12-hour sustained-release oral morphine ( SRM ) formulation . PATIENTS AND METHODS This was a double-blind , placebo-blinded , crossover study in 34 adult male and female out patients with pain due to advanced cancer . Baseline data were collected on day 1 . On days 2 and 3 , r and omly assigned patients received either placebo plus IRM ( Roxanol ; Roxane Laboratories , Inc , Columbus , OH ; 20 mg/mL ) at 2 , 6 , and 10 am , and 2 , 6 , and 10 pm , or alternatively SRM ( Oramorph SR ; Roxane Laboratories , Inc ; 30 mg ) at 10 AM and 10 PM . Patients were then crossed over to the alternate treatment for days 4 through 6 . Pain relief was measured using a conventional 100-mm visual analog scale ( VAS ) and by recording the incidence of breakthrough pain . Information on side effects was obtained from VAS scores for sedation , nausea , anxiety , and depression ; by directly question ing the patient as to mental confusion , bowel movements , and laxative use ; and from Karnofsky performance status scores . VAS data were analyzed using a linear statistical model . Breakthrough pain data were analyzed using analysis of variance ( ANOVA ) . RESULTS There were no statistically significant differences between IRM and SRM treatments with respect to VAS pain scores , side effect scores , or incidence of breakthrough pain data . Karnofsky performance scores remained stable for all patients throughout the study . CONCLUSION It was concluded that every-12-hour administration of SRM and every-4-hour administration of IRM provide similar analgesic effectiveness and side effect profiles in the treatment of chronic pain in cancer patients We assessed the quality of assessment and reporting of adverse effects in r and omized , double-blind clinical trials of single-dose acetaminophen or ibuprofen compared with placebo in moderate to severe postoperative pain . Reports were identified by systematic search ing of a number of bibliographic data bases ( e.g. , MEDLINE ) . Information on adverse effect assessment , severity and reporting , patient withdrawals , and anesthetic used was extracted . Compliance with former guidelines for adverse effect reporting was noted . Fifty-two studies were included ; two made no mention of adverse effects . No method of assessment was given in 19 studies . Twenty trials failed to report the type of anesthetic used , eight made no mention of patient withdrawals , and nine did not state the severity of reported adverse effects . Only two studies described the method of assessment of adverse effect severity . When all adverse effect data were pooled , significantly more adverse effects were reported with active treatment than with placebo . For individual adverse effects , there was no difference between active ( acetaminophen 1000 mg or ibuprofen 400 mg ) and placebo ; the exception was significantly more somnolence/drowsiness with ibuprofen 400 mg . Ninety percent of trials reporting somnolence/drowsiness with ibuprofen 400 mg were in dental pain . All studies published after 1994 complied with former guidelines for adverse effect reporting . Different methods of assessing adverse effects produce different reported incidence : patient diaries yielded significantly more adverse effects than other forms of assessment . We recommend guidelines for reporting adverse effect information in clinical trials The Brompton mixture is widely used as an effective method for controlling pain in cancer patients . In a double-blind crossover trial a st and ard Brompton mixture containing morphine , cocaine , ethyl alcohol , syrup BP and chloroform water was compared with morphine alone in a flavoured aqueous solution ; both were administered orally . Pain was measured by means of the pain intensity index of the McGill Pain Question naire . Ratings of confusion , nausea and drowsiness were obtained from both the patients and their nurses and relatives . The data showed that there was no significant difference between the Brompton mixture and morphine administered orally for any of the variables . Both relieved pain effectively in about 85 % of the patients Objetives The purpose of this study was to compare the analgesic efficacy and tolerability of opioids hydrocodone and tramadol in the relief of cancer pain . Methods One hundred and eighteen patients with chronic cancer pain participated in a double-blind , r and omized controlled trial . Sixty-two patients received hydrocodone and 56 patients received tramadol . Results Hydrocodone/acetaminophen was effective in relieving pain in 56.5 % of the patients at the starting dose of 25 mg/2500 mg/d . An additional 14.5 % of the patients responded to a double dose , and the remaining 29 % of patients did not experience any pain relief from hydrocodone administration . One dose of tramadol at 200 mg/d produced pain relief in 62 % of the patients and alleviated pain in another 11 % of patients at a dose of 400 mg/d , and remaining 27 % of patients did not experience pain relief from tramadol . No significant statistical difference in the analgesic efficacy of tramadol clorhydrate and hydrocodone/acetaminophen was found . The groups differed significantly in the incidence of side effects like nausea ( P=0.03 ; relative risk ( RR ) , 1.69 ; confidence interval ( IC ) 95 % , 1.03 - 2.77 ) , vomiting ( P=0.02 ; RR , 2.21 ; IC 95 % , 1.14 - 4.32 ) , dizziness ( P=0.03 ; RR , 2.12 ; IC 95 % , 1.17 - 3.86 ) , loss of appetite ( P=0.02 ; RR , 3.27 ; IC 95 % , 1.12 - 9.55 ) and weakness ( P=0.019 ; RR , 7.75 ; IC 95 % , 0.98 - 61.05 ) . Conclusions There was no superior analgesic efficacy with the administration of hydrocodone/acetaminophen when compared to patients receiving tramadol in the relief of cancer pain . Tramadol produced more mild side effects than hydrocodone This study was a prospect i ve , r and omized , open , crossover study comparing a double dose ( DD ) of normal-release ( NR ) morphine at bedtime with a single dose ( SD ) of NR morphine at bedtime and 4 h later . Twenty patients completed the study . Four patients required breakthrough analgesia during the SD phase of the study , whilst 11 patients required breakthrough analgesia during the DD phase of the study ( P=0.016 ) . Moreover , all of the pain scores were worse during the DD phase ( overnight pain , P < 0.01 ; morning pain , P<0.01 ) , and some of the opioid-related side effect scores were worse during the DD phase ( xerostomia , P=0.033 ; vivid dreams , P=0.05 ) . This study does not support the European Association for Palliative Care ( EAPC ) recommendations on the use of a double dose of NR morphine at bedtime SUMMARY Objective : This r and omised , multicentre , direct open comparative trial evaluated the efficacy , treatment convenience , tolerability and safety aspects of transdermal therapeutic system (TTS)-fentanyl and sustained-release oral morphine ( SRM ) in both opioid-naïve patients with moderate-to-severe cancer-related pain and in patients who had already been using opioids for mild-to-moderate pain . The two treatment groups were run in parallel . Special attention was paid to constipation , nausea/vomiting , drowsiness and respiratory depression . Patients and methods : The 131 enrolled patients started the 4-week treatment at low doses of opioid ( 25 μg/h TTS-fentanyl for 3 days or 30 mg SRM every 12 h ) and were individually titrated . Tolerability , efficacy and safety were assessed throughout the study period . Frequency of constipation was the primary study variable and accordingly the study was powered for this . Both patients and investigators made a global treatment evaluation . Results : TTS-fentanyl and SRM were shown to be equally effective . Pain control and sleep quality improved with both treatments . None of the patients developed respiratory depression . Statistically significantly more patients in the SRM treatment group discontinued the trial prematurely ( 59 % vs 27 % ; p < 0.001 ) , particularly due to adverse events ( 36 % vs 4 % ; p < 0.001 ) . Fewer patients in the TTS-fentanyl than in the SRM treatment group reported constipation during the trial . This finding was statistically significant after 1 week of treatment ( 27 % vs 57 % ; p = 0.003 ) . The favourable tolerability profile of TTS-fentanyl was also reflected in both the patient and the investigator global evaluation of the treatment . Patient assessment favoured TTS-fentanyl treatment in terms of a significantly lower rate of troublesome side-effects ( ‘ quite a bit ’ to ‘ very much ’ troublesome side-effects in 14 % vs 36 % of patients ; p = 0.003 ) and less interruption of daily activities ( absence of any interruption of daily activities in 88 % vs 63 % of patients ; p = 0.012 ) . Investigators scored TTS-fentanyl as significantly better with respect to ‘ side-effects ’ ( p = 0.039 ) and ‘ overall impression ’ ( p = 0.013 ) . Sub-analyses of opioid-naïve users gave similar results . Conclusion : These data indicate that TTS-fentanyl , when used as an opioid of first choice in the treatment of cancer-related pain , is as effective as , but better tolerated than , SRM , including in opioid-naïve patients Kadian/Kapanol ( K ) is a capsule formulation of morphine design ed for 12- or 24-hourly dosing . This double-blind study compared the efficacy and safety of K every 24 hr to K every 12 hr and MS Contin tablets ( MSC ) every 12 hr . One hundred fifty-two patients with cancer pain were titrated to adequate analgesia with immediate-release morphine ( IRM ) solution . Stabilized patients were r and onized to one of the three treatments for 7 + /- 1 days . Rescue medication was IRM tablets . Efficacy and safety were assessed by time to first remedication and total dose of rescue medication , pain scores , global assessment s , and incidence of morphine-related side effects . Fifty-four patients were treated with K every 24 hr . 45 with K every 12 hr . and 53 with MSC every 12 hr . Mean age was 61 years and mean total daily dose of morphine was 138 mg . Forty-six percent of the K every 24 hr patients , 51 % of the K every 12 hr patients , and 55 % of the MSC every 12 hr patients required rescue medication on the final day . Time to remedication was 16.0 hr for K every 24 hr , 9.1 hr for K every 12 hr and 8.7 hr for MSC every 12 hr ( P = 0.0010 ) . Patient global assessment significantly favored K every 24 hr over MSC every 12 hr ( P = 0.018 ) . There were no statistically significant differences among the treatments for any morphine-related side effects when adjusted for baseline . K had efficacy and safety profiles similar to MSC every 12 hr but had the advantage of 12- or 24-hourly administration In a double‐blind crossover study , morphine and oxycodone hydrochloride were administered to 20 patients who were experiencing severe cancer pain . The peroral doses were determined on the basis of patient‐controlled intravenous titration . The assumed oral bioavailability ratios were 44 % ( group 1 , first 10 patients ) and 33 % ( group 2 , last 10 patients ) for morphine and 66 % ( group 1 ) and 50 % ( group 2 ) for oxycodone hydrochloride , respectively . However , the patients were able to readjust their oral dosings . Equal analgesia was achieved with both drugs , but the intravenous dose of oxycodone hydrochloride needed was 30 % higher than that of morphine . The median calculated oral/intravenous ratios giving comparable analgesia were 0.31 for morphine and 0.70 for oxycodone hydrochloride . Morphine caused more nausea than oxycodone hydrochloride and hallucinations occurred only during morphine treatment . Otherwise , there were no major differences in the side effects between these two opioids The efficacy , safety , and pharmacokinetics of a novel once-daily morphine formulation ( OAD morphine ) and a 12-hourly formulation ( twice-daily CR morphine ) were compared in a double-blind , multi-centered crossover study . Chronic cancer pain patients ( n=25 ) were r and omized to OAD morphine ( mean 238 + /- 319 mg q24h ) or twice-daily CR morphine ( mean 119 + /- 159 mg q12h ) for one week . They then crossed over to the alternate drug , which also was taken for one week . There was no difference between treatments for evaluations of overall pain intensity , analgesic efficacy , or adverse events . However , whereas pain scores increased during the day on twice-daily CR morphine ( P=0.0108 ) , they remained stable on OAD morphine . Most patients ( 68 % ) chose once-daily dosing for continuing pain management ( P=0.015 ) . The AUC ratio was 100.3 % , indicating equivalent absorption . Fluctuation indices were 93.5 + /- 28.8 % and 179.3 + /- 41.3 % ( P=0.0001 ) for OAD morphine and twice-daily CR morphine , respectively . OAD morphine provides analgesia similar to twice-daily CR morphine with reduced fluctuation in plasma morphine concentration and more stable pain control Diurnal variation in pain perception is recognized . The question of whether opioid prescribing should be adjusted to account for diurnal variation can be tested with the advent of once-daily sustained-release morphine . The study recruited 45 people with opioid-responsive pain on stable doses of analgesics and advanced cancer from five regional palliative care programs in Australia . Each participant took one placebo and a 24-hourly dose of sustained-release morphine daily , 12 hours apart-active dose in the morning for one week and in the evening for the other week . The order of the weeks was r and omized in a double-blind manner . The primary outcome from the last two days ( steady state ) on both arms was averaged four-hourly pain scores while awake on a 100 mm visual analogue scale ( VAS ) . Secondary outcomes included VAS and categorical scales for other pain parameters , quality of sleep , nausea , vomiting , constipation , confusion , and somnolence . Twenty-six of 42 participants completed the study and provided adequate power for analysis . Mean VAS was 16 mm for morning dosing and 14 mm for evening dosing ( P=0.76 , difference of adjusted means 2 mm , 95 % confidence interval : -2 , 6 ) . No differences were found in pain control , pain during the day , pain disturbing sleep , or with breakthrough medication use . This study suggests that any difference between morning and evening dosing of once-daily sustained-release morphine in people with significant opioid-responsive pain and advanced cancer is small and unlikely to be clinical ly significant for most people SUMMARY Objective : To compare the analgesic efficacy and safety of oxymorphone extended release ( ER ) and oxycodone controlled release ( CR ) in patients with moderate to severe cancer pain . Research design and methods : This r and omized , multicenter , double-blind , 2-period crossover study included adult out patients ( ≥ 18 years of age ) with moderate or severe cancer pain who were first titrated for 3–10 days with open-label oxymorphone or oxycodone to achieve a stable dose that provided adequate analgesia with tolerable adverse events and no requirement for more than 2 doses of rescue medication per day . The subsequent double-blind treatment phase was a 7- to 10-day period of oxycodone CR or oxymorphone ER treatment followed by crossing over to the alternate medication for another 7–10 days . During the treatment phase , up to 2 doses per day of morphine sulfate 15-mg tablets were allowed as rescue . Main outcomes and measures : Assessment s included the Brief Pain Inventory , global evaluations , Karnofsky performance status , and clinical laboratory evaluations ( serum chemistry profile , complete blood count , urinalysis ) . Efficacy variables were analyzed using a mixed-effects model with treatment , sequence , and period as fixed effects and subject as a r and om effect . Results : Forty-seven patients entered the titration/stabilization phase , 44 received at least 1 dose of study drug , 42 completed the first double-blind phase , and 40 completed the second double-blind phase . Mean pain intensity scores and other efficacy parameters were comparable for the 2 groups . The mean daily dosage of oxycodone CR ( 91.9 mg ) was twice that of oxymorphone ER ( 45.9 mg ) , an equianalgesic dose ratio of 2:1 . Rescue medication use was low in both groups ( approximately 1 tablet of morphine sulfate 15 mg/day ) . No significant differences in opioid adverse events were observed between the groups . Conclusions : Adult patients with cancer who were taking oxycodone CR were readily converted to oxymorphone ER and required half the milligram dose to stabilize their pain . Within 72 h , most patients achieved a stable dose that provided adequate relief with similar opioid adverse events In order to determine the optimal pain treatment for patients with cancer involvement of the brachial or lumbar nerve plexuses , a prospect i ve comparative study was carried out using peroral opioid therapy ( SO ) , epidural opioid by a conventional tunnelled epidural catheter ( CE ) or an epidural catheter connected to an implanted injection port ( Port ) . Pain relief , measured by a visual analog scale ( VAS ) , was similar and adequate in every group already after the first 24 h. CNS side – effects were less frequent and the Karnofsky performance grade s slightly superior in the epidural groups . Occlusion and catheter disconnection complicated the pain therapy of five epidural port patients . Epidural dislocation occurred three times in the conventional epidural group . One local infection in the CE group and two in the Port group were recorded . However , no signs of epidural infection were seen at autopsy . The results suggest that due to a lower incidence of side – effects , epidural catheter techniques are superior to peroral opioid in treating pain in these patients . However , complete pain relief was not achieved in all patients , suggesting neurogenic , non – nociceptive pain components . Both epidural techniques seem suitable for long – term pain therapy . Technical improvements are needed in the epidural catheter and the port . The long – term epidural catheter does not seem to cause any major changes in the histology of the dura mater or the connective tissue of the epidural space A cross-over , single blind trial of MST and MSS in relieving pain of advanced cancer patients is described . Forty-nine cases completed the study . Both MST and MSS gave equally excellent pain relief in the patients as judged by the pain score of VAS and pain rating scale by a nurse , and the duration of sleep . The daily effective dose was 55.5 + /- 19.7 mg for MST and 61.0 + /- 11.0 mg of MSS The use of oxycodone to treat chronic cancer pain has been hampered by its short elimination half‐life , which necessitates administration every 4 hours . This study compared the clinical efficacy and safety of a novel oxycodone formulation with that of hydromorphone in the treatment of cancer pain The transdermal therapeutic system ( TTS ) for fentanyl is a drug-delivery system for use in patients with chronic pain who require an opioid analgesic . A multicentre , r and omized , double-blind , placebo-controlled study was performed to evaluate the efficacy and safety of TTS-fentanyl as an analgesic for chronic cancer pain . One hundred and thirty-eight patients entered a 15-day dose-titration period , followed by a 9-day double-blind period ( 95 patients ) with TTS-fentanyl or placebo . Fifty-five patients entered a follow-up period of indefinite duration . For the majority of patients , TTS-fentanyl 50 - 75 µg/h provided effective analgesia . Due to an unexpectedly high placebo response , it was not possible to show fentanyl to be statistically superior to placebo at the 5 % significance level . Nine patients treated with fentanyl and 13 treated with placebo were withdrawn from the study during the double-blind therapy because of insufficient efficacy ( not significant ) , while 66 % of fentanyl-treated patients experienced effective pain control compared with 48 % of placebo-treated patients ( p=0.071 ) . During the course of the double-blind therapy , the mean dose of rescue morphine increased slightly more in the placebo group than in the fentanyl group . At the end of the double-blind phase , the investigators rated trial medication as being ' good ' or ' excellent ' in 30 patients in the fentanyl group and 23 in the placebo group . TTS-fentanyl appeared to be well tolerated , with a low incidence of constipation , somnolence and nausea . Due to an unexpectedly high placebo response it was not possible to demonstrate fentanyl to be statistically superior to placebo . This may reflect the practical difficulties of performing clinical trials in cancer patients with great inter-individual variability . Copyright 1998 European Federation of Chapters of the International Association for the Study of Pain It is uncertain whether there exists a nociceptive component in malignant nerve pain responsive to NSAIDs and opioids . 20 patients with malignant nerve pain were r and omly assigned to treatment with naproxen 1500 mg versus slow-release morphine 60 mg daily during 1 week , followed by cross-over medication during the second week in a double-blind , double-dummy protocol . In the 16 evaluable patients , a significant ( P < 0.05 ) reduction of 26 % ( S.E. + /- 7.9 ) in pain intensity was reached at day 7 , compared to baseline pain . At day 7 , significant pain relief of 32 % ( P < 0.05 ) was observed in the naproxen group , but not in the morphine group ( 21 % , P = 0.14 ) . Patients using morphine needed approximately twice as much paracetamol rescue than patients using naproxen . Additional pain relief could be observed in 4/9 patients with cross-over medication . These data support the concept of a nociceptive component in malignant nerve pain responding to NSAIDs and opioids , and favour the combination of both an anti-inflammatory drug and an opioid for symptomatic pain relief PURPOSE The aim of this study was to compare the analgesic and adverse effects , doses , as well as cost of opioid drugs , supportive drug therapy and other analgesic drugs in patients treated with oral sustained-release morphine , transdermal fentanyl , and oral methadone . PATIENTS AND METHODS One hundred and eight cancer patients , no longer responsive to opioids for moderate pain , were selected to r and omly receive initial daily doses of 60 mg of oral sustained-release morphine , 15 mg of oral methadone , or 0.6 mg ( 25 microg/h ) of transdermal fentanyl . Oral morphine was used as breakthrough pain medication during opioid titration . Opioid doses , pain intensity , adverse effects , symptomatic drugs , were recorded at week intervals for 4 weeks . Costs of opioid therapy , supportive drugs , and other analgesic drugs were also evaluated . RESULTS Seventy patients completed the 4 weeks period of study . Five , five , and four patients , treated with oral morphine , transdermal fentanyl , and oral methadone , respectively , required opioid switching . No differences in pain and symptom intensity were observed . Opioid escalation index was significantly lower in patients receiving methadone ( p<0.0001 ) , although requiring up and down changes in doses . At the doses used , methadone was significantly less expensive ( p<0.0001 ) , while the use and costs of supportive drugs and other analgesics were similar in the three groups . No relevant differences in adverse effects were observed among the groups during either the titration phase and chronic treatment . CONCLUSION All the three opioids used as first-line therapy were effective , well tolerated , and required similar amounts of symptomatic drugs or co-analgesics . Methadone was significantly less expensive , but required more changes , up and down , of the doses , suggesting that dose titration of this drug requires major clinical expertise Nineteen cancer patients with chronic pain of moderate to severe intensity were r and omized in a double-blind manner to 5 days of either 8-hourly or 12-hourly administration of controlled-release morphine ( MS Contin , MSC ) , followed by the alternate schedule for 5 days . The control of pain , using an average dose of 303.4 + /- 254.4 mg/day of MSC , was good during both the 8-hourly and 12-hourly phases , and the mean daily pain intensity measured by visual analogue scale ( VAS ) , pain relief ( VAS ) , and global efficacy scores did not differ when compared by treatment schedule . The need for supplemental " rescue " morphine was infrequent and did not differ between treatment phases ( 8-hourly , 0.7 + /- 0.7 and 12-hourly , 0.6 + /- 0.6 doses per day , p = 0.6232 ) . The overall frequency and severity of adverse events did not differ between the two dosing schedules . A majority of patients ( 67 % ) reported that they believed that 12-hourly dosing was a moderate or great advantage over 8-hourly dosing Fifty‐one cancer pain patients with limited opioid exposure participated in a r and omized , double‐blind , repeated‐dose , parallel‐group comparison of two dosage strengths of the controlled‐release morphine preparation , MS Contin tablets ( The Purdue Frederick Company , Norwalk , CT ) . The patients were first stabilized on immediate‐release oral morphine 30 mg every 4 hours , with 15 mg available every 2 hours as needed for breakthrough pain ( “ rescue ” dose ) . Each patient then received either one 100 mg MS Contin tablet or three 30‐mg MS Contin tablets every 12 hours , with rescue medication as needed , for 3 days . Analysis of study power revealed sufficient sensitivity to detect clinical ly relevant differences in pain intensity and use of rescue medication . The two tablet strengths yielded similar pain relief , use of rescue medication , and frequency of side effects . In addition , pain and use of rescue medication did not change from the beginning to the end of the 12‐hour dosing intervals in either group . In the study population as a whole , pain intensity was lower and total morphine intake higher during the period on controlled‐release morphine . These data establish comparable analgesic efficacy and side effect potential of these two dosage strengths and confirm a 12‐hour duration of effect for both . The improved analgesia on the controlled‐release morphine may be attributable to increased consumption of drug result ing from improved compliance Controlled-release oral formulations of oxycodone and morphine are both suitable analgesics for moderate to severe pain . They were compared in cancer-pain patients r and omized to double-blind treatment with controlled-release oxycodone ( n = 48 ) or controlled-release morphine ( n = 52 ) every 12 h for up to 12 days . Stable analgesia was achieved by 83 % of controlled-release oxycodone and 81 % of controlled-release morphine patients in 2 days ( median ) . Following titration to stable analgesia , pain intensity ( 0=none to 3=severe ) decreased from baseline within each group ( p < /= 0.005 ) , from 1.9 ( 0.1 ) to 1.3 ( 0.1 ) , mean ( SE ) , with controlled-release oxycodone , and from 1.6 ( 0.1 ) to 1.0 ( 0.1 ) with controlled-release morphine ( no significant between-group differences ) . Typical opioid adverse experiences were reported in both groups . Hallucinations were reported only with controlled-release morphine ( n = 2 ) . Visual analog scores ( VAS ) for ' itchy ' and ' scratchin ' were lower with controlled-release oxycodone ( p < /= 0.044 ) , as was peak-to-trough fluctuation in steady-state plasma concentration ( p = 0.004 ) . The correlation between plasma concentration and dose was stronger ( p = 0.026 ) for oxycodone ( 0.7 ) than morphine ( 0.3 ) . The relationship between pain intensity ( VAS ) and plasma concentration was more positive for oxycodone ( p = 0.046 ) . There was a positive relationship between morphine-6-glucuronide concentrations and urea nitrogen and creatinine levels ( p = 0.001 ) . Controlled-release oxycodone was as effective as controlled-release morphine in relieving chronic cancer-related pain , and as easily titrated to the individual 's need for pain control . While adverse experiences were similar , controlled-release oxycodone was associated with less itching and no hallucinations . Controlled-release oxycodone provides a rational alternative to controlled-release morphine for the management of moderate to severe cancer-related pain PURPOSE The aim of this double-blind , double-dummy , crossover study was to compare the efficacy , tolerability , and time of onset of analgesia after the administration of 10 mg of morphine hydrochloride via the oral and rectal routes in opioid-naive cancer patients with pain . PATIENTS AND METHODS Thirty-four patients with cancer pain and no previous opioid treatment were r and omized to receive morphine hydrochloride 10 mg orally or rectally ( in the form of a microenema ) for 2 days . During days 3 and 4 , a crossover took place . The scores of pain , nausea , and sedation ( visual analog scale of 0 to 100 ) calculated as the percentage change from baseline ( before opioid administration ) were assessed at different intervals up to 240 minutes . The number of vomiting episodes was recorded . Parity tests and analysis of variance ( ANOVA ) were performed to compare the two administration routes . RESULTS A significant difference in pain intensity was achieved 10 minutes after rectal administration compared with 60 minutes after oral administration . There was still a significant reduction in pain via the rectal route after 180 minutes versus via the oral route after 120 minutes . No significant difference was observed in the intensity of sedation , nausea , or number of vomiting episodes between the oral and rectal routes . CONCLUSION A liquid solution of morphine is well absorbed via the rectal route . Rectal morphine is safe , effective , easy to manage , and inexpensive , with a rapid onset of action . Rectal morphine can be considered a valid alternative route for opioid administration and may also be used when rescue doses of morphine are required in patients regularly treated with oral or parenteral opioids PURPOSE How r and omized controlled trial results are reported may minimize concerns and detection of adverse side effects . We aim ed to describe the methods of reporting adverse events in these published trials . METHODS Five frequently cited journals were investigated : Annals of Internal Medicine , British Medical Journal , JAMA , The Lancet , and the New Engl and Journal of Medicine . For each journal , all r and omized controlled trials conducted on the use of a medication were selected from January 2000 through June 2003 . All issues of each journal were review ed manually . Information retrieved included any mention of adverse events in the abstract , methods , results , or discussion section of the article ; or inclusion of adverse events data in tables or figures . We also cataloged whether there was a separate subheading in the results section for reporting adverse events . Reports of trials that referred to methods described in a previous report were excluded . RESULTS There were 521 eligible articles . Explicit mention of adverse events was in 328 ( 63 % ) of abstract s ( range 47 - 66 % ) , 380 ( 73 % ) of methods ( range 51 - 81 % ) , 464 ( 89 % ) of results ( range 80 - 95 % ) , and 250 ( 48 % ) of tables ( range 31 - 49 % ) . There was a separate subheading for adverse events in 240 ( 46 % ) ( range 22 - 64 % ) of the eligible articles . CONCLUSION There is variation among authors and journals as to the location of reporting adverse events and the means by which it is done . Authors and editors should include specific information on adverse events when reporting the results of r and omized controlled trials . It would be ideal if there was more consistency among authors and journals as to how these adverse events are described Nineteen of 25 patients ( 14 female ) with advanced malignant disease completed a r and omized controlled trial of a new high-dose ( 200 mg ) tablet formulation of controlled-release morphine . Compared with the currently available 100-mg tablets there were no differences in pain severity or adverse effects with the new formulation . In four patients , full 12-hr plasma morphine concentration profiles at steady state were obtained and showed no significant differences between the same dose provided as 100-mg and 200-mg tablets in Cmax , tmax , or other pharmacokinetic indices & NA ; Controlled‐release ( CR ) formulations of oxycodone and morphine were compared in 45 patients with chronic cancer pain . The study was started with an open‐label , r and omised titration phase to achieve stable pain control for at least 48 h , followed by a double‐blind , r and omised , crossover phase in two periods , 3–6 days each . To blind the study using available tablet strengths , the dose ratio of oxycodone to morphine was set at 2:3 . A daily telephone contact was maintained between the patient and the investigator . The patients were asked to assess pain intensity four times a day and acceptability of therapy twice daily , and to record possible adverse effects . Pharmacodynamic evaluations were performed at the end of each double‐blind period . The patients were allowed to use escape analgesic ( respective opioid as oral solution ) as needed . Twenty‐seven patients were evaluable for both safety and efficacy . Pain was well‐controlled during both stable phases . When the period effect was taken into account the two opioids provided comparable analgesia . If the results of the two periods were combined , the patients consumed significantly more escape doses and the mean pain intensities were significantly greater with CR oxycodone . The total opioid consumption ratio of oxycodone to morphine was 2:3 when oxycodone was administered first , and 3:4 when oxycodone was administered after morphine . The total incidence of adverse experiences reported by the patients was similar , but significantly more vomiting occurred with morphine , whereas constipation was more common with oxycodone Purpose : Several sustained-release morphine ( SRM ) formulations are available internationally . This study compared 2 such products available in the United States , SR1 and SR2 . Patients and Methods : In an open-label study , patients with advanced cancer pain were r and omized to receive SR1 or SR2 every 12 hours around-the-clock ( ATC ) for 5 days , with immediate release ( IR ) liquid morphine for rescue dosing ( RD ) . Efficacy , safety , and patient acceptability were determined . Results : A total of 32 patients were evaluable for efficacy and toxicity . Pain scores , RD dosage , RD frequency over 5 days , RD within 3 hours before and after the scheduled SRM , and 8 of the 11 evaluated side effects were higher in the SR1 group . At presumed morphine steady state ( day 3 ) , pain scores ( P = .05 ) , RD dosage ( P = .07 ) , RD frequency ( P = .07 ) , and number of RD ±3 hours from scheduled SRM dose ( P = .05 ) were consistently greater in the SR1 group ( despite a higher median morphine dose in that group ) . There was a clinical ly important and directionally consistent trend that favored SR2 , although not all were statistically significant . Patient preference favored SR2 ( P < .05 ) . Neither group had difficulty swallowing SR1 or SR2 . Conclusions : This is the first study that directly compared two 12-hour SRM formulations . The data suggested , by multiple clinical ly important measures , that SR2 may provide superior analgesic efficacy and less toxicity compared to SR1 . It also supports the concept that it can not be assumed that different SR formulations of a given opioid are clinical ly equivalent . A larger study is needed to confirm our findings Summary Kapanol ™ is a capsule formulation of morphine design ed for 12- or 24-hourly administration . This multicentre , r and omised , open-label , parallel study compared the efficacy and tolerability of 12-hourly Kapanol ™ 1 with morphine sulfate controlled-release tablets ( MST ® 2 ) . Patients with severe chronic pain ( n = 165 ) of various origins ( 73.5 % nonmalignant ) were r and omised and titrated to adequate analgesia with Kapanol ™ or MST ® , respectively . Once stabilised , patients started the 2-week study period . Rescue medication was available as necessary ( immediate-release morphine 10 mg tablets ) . Efficacy and tolerability were assessed by a final physician assessment , rescue medication requirement , pain scores , quality of sleep , and incidence of morphine-related adverse effects . Although 112 patients completed the study , 22 of 91 ( 24.2 % ) patients on Kapanol ™ and 31 of 74 ( 41.9 % ) patients on MST ® withdrew prematurely . Inadequate efficacy was the reason for premature termination in 5 patients in the Kapanol ™ group and 13 patients in the MST ® group . Patient demographics were similar in the two groups . Kapanol was shown to be significantly better than MST ® , based on final physician assessment ( p = 0.02 ) , quality of sleep ( p = 0.05 ) , and effect on mood ( p < 0.05 ) . Morphine-specific adverse effects occurred with similar frequency in both groups . This study found that the continuous and sustained release of morphine achieved by the novel Kapanol ™ formulation was more effective than MST ® in managing severe chronic pain of both malignant and nonmalignant origin Eighteen of 27 patients with pain due to advanced cancer , completed a r and omised crossover comparison of4‐hourly aqueous morphine sulphate and twice daily controlled release morphine tablets . There was no difference between the two regimens in analgesic efficacy or adverse effects , but there was an apparent improvement in quality of sleep on the controlled release tablets . After completion of the study , 17 patients continued with the latter medication for periods that ranged from 2 days to 94 weeks ( median 6.5 weeks ) . Controlled release morphine tablets given twice daily provide a simpler and more convenient treatment regimen than a 4‐hourly opioid for patients with cancer pain , once they have been stabilised BACKGROUND The quality of care provided to patients with cancer who are dying in hospital and their families is suboptimum . The UK Liverpool Care Pathway ( LCP ) for patients who are dying was developed with the aim of transferring the best practice of hospices to hospitals . We therefore assessed the effectiveness of LCP in the Italian context ( LCP-I ) in improving the quality of end-of-life care for patients with cancer in hospitals and for their family . METHODS In this pragmatic cluster r and omised trial , 16 Italian general medicine hospital wards were r and omly assigned to implement the LCP-I programme or st and ard health-care practice . For each ward , we identified all patients who died from cancer in the 3 months before r and omisation ( preintervention ) and in the 6 months after the completion of the LCP-I training programme . The primary endpoint was the overall quality of care toolkit scale . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT01081899 . FINDINGS During the postintervention assessment , data were gathered for 308 patients who died from cancer ( 147 in LCP-I programme wards and 161 in control wards ) . 232 ( 75 % ) of 308 family members were interviewed , 119 ( 81 % ) of 147 with relatives cared for in the LCP-I wards ( mean cluster size 14·9 [ range eight to 22 ] ) and 113 ( 70 % ) of 161 in the control wards ( 14·1 [ eight to 22 ] ) . After implementation of the LCP-I programme , no significant difference was noted in the distribution of the overall quality of care toolkit scores between the wards in which the LCP-I programme was implemented and the control wards ( score 70·5 of 100 vs 63·0 of 100 ; cluster-adjusted mean difference 7·6 [ 95 % CI -3·6 to 18·7 ] ; p=0·186 ) . INTERPRETATION The effect of the LCP-I programme in our study is less than the effects noted in earlier phase 2 trials . However , if the programme is implemented well it has the potential to reduce the gap in quality of care between hospices and hospitals . Further research is needed to ascertain what components of the LCP-I programme might be effective and to develop and assess a wider range of approaches to quality improvement in hospital care for people at the end of their lives and for their families . FUNDING Italian Ministry of Health and Maruzza Lefebvre D'Ovidio Foundation-Onlus PURPOSE Use of oxycodone for chronic cancer pain has been hampered by its short elimination half-life . This study was design ed to compare the efficacy and safety of controlled-release formulations of oxycodone and morphine for cancer pain . PATIENTS AND METHODS Thirty-two adult patients with cancer pain and a > or = 3-day history of stable analgesia with oral opioids provided written informed consent and were r and omized to controlled-release oxycodone or controlled-release morphine for 7 days . To blind the study using available tablet strengths , the dose ratio of oxycodone to morphine was set at 1:1.5 . On day 8 , patients were crossed over to the alternate drug for 7 days . Pain intensity was assessed using a visual analog scale ( VAS 0 to 100 mm ) and a categorical scale ( CAT 0 to 4 ) . Side effects were assessed using a checklist ( four-point categorical severity ) and a nondirected question naire . Patients and investigators made blinded global ratings of efficacy and treatment preference . RESULTS Twenty-three patients completed the study ( 10 men , 13 women ) . The VAS and CAT scores were ( mean+/-SD ) 23+/-21 and 1.2+/-0.8 on controlled-release oxycodone , and 24+/-20 ( P=.43 ) and 1.3+/-0.7 ( P=.36 ) on controlled-release morphine . No period or carryover effect was detected . There were no significant differences in adverse effects ( P=.40 ) or ratings of efficacy and preference . The median oxycodone/morphine dose ratio was 1.5 and the maximum was 2.3 . CONCLUSION Controlled-release oxycodone is as safe and effective as controlled-release morphine in the treatment of cancer pain The relative analgesic potency of oral and intramuscular codeine was evaluated in a double-blind crossover comparison of grade d single doses in patients with chronic pain due to cancer . When both duration and intensity of analgesia are considered ( total effect ) , oral codeine was 6/10 as potent as the intramuscular form . This is a high oral/parenteral analgesic relative potency ratio compared with morphine , metopon and oxymorphone and correlates well with the results of recent studies which have determined the oral vs. intramuscular bioavailability of codeine in man . Oral and intramuscular oxycodone were also compared in a similar patient group . Like codeine , oxycodone retained at least 1/2 of its analgesic activity when administered orally . We hypothesize that the high oral/parenteral relative potency ratios of codeine and oxycodone relative to morphine and its congeners are not due to more efficient absorption after oral administration , but rather that methylation at position 3 in codeine and oxycodone protects these drugs from rapid first-pass metabolism Abstract Twenty‐four patients with severe pain related to cancer completed a r and omised , double‐blind , double‐dummy , crossover study examining morphine pharmacokinetics and pharmacodynamics when the same 24‐h morphine dose was administered using two modified release oral morphine formulations ; either one dose of KapanolTM ( a new sustained release polymer coated pellet formulation administered in capsule form , Glaxo Wellcome group of companies ) per 24 h , or MS Contin ® ( Purdue Frederick Company , Connecticut , USA ) administered at 12‐h intervals . The morphine dose was optimised for each patient using an immediate release morphine solution in the lead‐in period to provide the most favourable balance between pain relief and side‐effects . Patients were then r and omly allocated to receive their 24‐h morphine dose as either Kapanol or MS Contin in period 1 . Patients recorded daily measures of pain relief and morphine related side‐effects ( morphine pharmacodynamics ) in a diary . Patients were admitted to the Pain Management Unit on the morning of day 7 ( ±1 day ) and frequent blood sample s were collected for 24 h following the 10:00 h dose to fully characterise the pharmacokinetic profile for morphine and its metabolites at steady state . Morphine pharmacodynamics and the amount and timing of rescue medication ( dextromoramide ) were also recorded during this time . Period 2 , which commenced at 10:00 h on day 8 , was identical to period 1 except the modified release formulations were changed . The pharmacokinetic profile of Kapanol exhibited a significantly higher Cmin ( minimum plasma morphine concentration ) , less fluctuation in plasma morphine concentration throughout the dosing interval , a longer Tmax ( time associated with the maximum morphine concentration ) and a greater time that the plasma morphine concentration was ≥75 % of Cmax ( an index of the control the formulation exerts over the morphine release rate ) compared to that of MS Contin . Some of these pharmacokinetic differences ( e.g. , Cmin and fluctuation in plasma morphine concentration ) were surprising given that the dosing interval for Kapanol ( 24 h ) was double that of MS Contin ( 12 h ) . There was no significant difference between the Kapanol and MS Contin treatment phases in any of the pharmacodynamic parameters , morphine related side‐effects , the percentage of patients taking rescue medication as well as the amount or time to the first dose of rescue analgesia on day 7 in periods 1 and 2 , patient or investigator assessment s of global efficacy at the end of periods 1 and 2 , or patient treatment preference at the end of the study . Once a day Kapanol provided the same degree of pain relief and morphine related side‐effects as 12‐h MS Contin Two consecutive , r and omized , double‐blind trials were performed to test the analgesic properties of a synthetic nitrogen analog of tetrahydrocannabinol ( NIB ) . In the first trial , the test preparation was superior to placebo and approximately equivalent to 50 mg of codeine phosphate . In the second study , the tetrahydrocannabinol analog was superior to placebo and to 50 mg secobarbital . NIB is not useful clinical ly because of the frequency of side effects BACKGROUND Analgesics are an essential component of the treatment of cancer-associated pain . Pharmacologic treatment is usually begun with nonopioid analgesics , most frequently acetaminophen . If pain relief is not achieved , the so-called " weak " opioids , such as codeine and hydrocodone , may be used in combination with acetaminophen . Adverse effects ( AEs ) of the opioids include constipation , somnolence , nausea , and vomiting . Based on the results of a literature search , data comparing the effects of the opioids are lacking . OBJECTIVE The purpose of this study was to compare the analgesic efficacy and tolerability of codeine phosphate versus hydrocodone bitartrate in combination with acetaminophen in the relief of cancer-related pain . METHODS This 23-day , prospect i ve , double-blind , r and omized , parallel-group study was conducted at 3 Colombian centers : University Libre , Social Security Institute , and General Hospital of Medellín , Cali , Colombia . Out patients with cancer were eligible for the study if they were aged > -18 years and had chronic ( duration , > /= 3 months ) moderate to severe cancer-related pain ( score on 10-cm visual analog scale [ VAS ] , > 3 cm [ moderate ] ; score on a 4-point verbal pain-intensity scale , > 1 [ moderate ] ) . Eligible patients were r and omly assigned to receive 1 tablet of codeine/acetaminophen ( C/A ) 30/500 mg or hydrocodone/acetaminophen ( H/A ) 5/500 mg PO q4h ( total daily doses , 150/2500 and 25/2500 mg , respectively ) for 23 days . In both groups , if pain intensity was rated as > 3 on the VAS at week 1 or 2 , the dosage was doubled . The primary end point was the proportion of patients who achieved pain relief ( defined as a score of > 1 on a 5-point verbal rating scale [ VRS ] ( 0 = none ; 1 = a little ; 2 = some ; 3 = a lot ; and 4 = complete ) on study days 1 and 2 and weeks 1 , 2 , and 3 . The secondary end point was the proportion of patients in whom pain was decreased ( VAS score , < - 3 cm ) . AEs were self-reported on a 4-point VRS ( 0 = absent ; 1 = mild ; 2 = moderate ; and 3 = severe ) . RESULTS Of the 121 patients who participated , 59 received C/A and 62 received H/A. Of the total number of cases , 59 % were aged 60 to 89 years , and 55 % were men . At baseline , 88 % of the patients described their pain intensity as moderate ; 12 % , severe . Of the patients who received C/A , 58 % responded to the initial dosage of 150/2500 mg/d , and 8 % of the patients responded to the double dosage ; 34 % did not experience pain relief . In patients with H/A , pain was reported as absent or mild in 56 % of patients at the starting dosage of 25/2500 mg/d ; an additional 15 % of the patients responded to the double dosage ; the remaining 29 % of patients did not experience any pain relief . None of the between-group differences in response rates were significant . The most common AEs in the C/A and H/A groups were constipation ( 36 % and 29 % , respectively ) , dizziness ( 24 % and 19 % ) , vomiting ( 24 % and 16 % ) , and dry mouth ( 15 % and 18 % ) , with no significant differences between groups . CONCLUSION In this study , efficacy and tolerability were comparable between C/A and H/A over 23 days of treatment in these patients with moderate or severe , chronic , cancer-related pain This r and omized controlled trial compared intravenous route with oral route for initial dose titration of morphine in 62 patients with end-stage cancer and severe pain . Patients in the intravenous group received 1.5 mg intravenous bolus doses of morphine every ten minutes till pain relief was total or until they became drowsy . After that they got oral morphine at a dose equal to the total initial intravenous requirement four-hourly . Patients in the oral group got oral morphine 5 mg doses ( if opioid-naÖve ) or 10 mg ( if already on weak opioid ) four hourly . Patients in both groups had the option to receive rescue doses of their regular oral dose as and when needed , if necessary hourly . Twenty-seven of 31 in the intravenous group had either total or satisfactory pain relief by the end of one hour , whereas only eight of 31 in the oral group had a similar result . After 24 hours and later both groups had similar results . There was no immediate serious side effect in any of the patients . The late side effects were similar in the two groups . In the intravenous group , the ratio of initial intravenous dose requirement to the subsequent regular single oral dose after two days centred around 1:1 ( range 1:0.5 - 1:3.3 ) . This study found the intravenous method to be safe , effective and superior to the traditional method in providing immediate relief to severe cancer pain Abstract Over a period of 14 days , 54 patients with incurable chronic cancet pain were observed : 27 were r and omized for treatment with morphine per os and 27 with methadone per os . Data regarding daily dosage , analgesic effects , hours of sleep , hours st and ing , performance status ( PS ) and side effects were collected during both treatments . The results show overlapping analgesic efficacy and side effects for both drugs , and confirm the hypothesis that lower doses of methadone are required than morphine . In the treatment with methadone , the initial average dose was 18 mg , and this dose was maintained throughout the entire period , whereas the initial average daily dose of morphine was 72.74 mg ( ±39.25 ) , and the final average daily dose was 119.40 mg ( ±79.1 ) . The findings in this study show that methadone is a valid alternative to morphine in cancer pain treatment even though , as a result of its pharmaceutical cha rct eristics , it requires a differnt titration for the patient With the objective of comparing incidence of adverse events of the opioids codeine , hydrocodone , and tramadol in the relief of cancer pain , we conducted a r and omized controlled trial in which patients with cancer were r and omly assigned according to a computer-generated schedule to receive one of the three opioids . Of the 177 patients who participated , 62 patients received hydrocodone , 59 patients received codeine , and 56 patients received tramadol . The pain experienced by the participants originated most frequently from the stomach , breast , or prostate gl and and was classified as either somatic ( 33 % ) , visceral ( 52 % ) , mixed ( 6 % ) , or neuropathic ( 9 % ) . At the first visit , 60 % of the patients described their pain intensity as moderate ( 4 - 6/10 ) , with the remaining 40 % of the patients describing their pain as severe ( 7 - 10/10 ) . The symptoms most associated with pain were weakness , insomnia . and anorexia . In 77 % of the total number of cases , the patient was aware of his/her diagnosis prior to admittance to the palliative care unit . Of the total number of cases , 57 % fell in the age range of 60 - 89 years old and 50 % of the participants were female . No significant statistical difference in the analgesic efficacy of the three opioids was found ( p : 0.69 ; chi(2 ) : 0.73 ) . Use of tramadol produced higher rates of adverse events than codeine and hydrocodone : vomiting , dizziness , loss of appetite , and weakness ( p < 0.05 ) The authors report the data from two studies on the use of controlled-release morphine sulphate tablets for cancer pain relief . This preparation allows just two administrations per day , in comparison with immediate release oral aqueous morphine solution . The first study , a r and omized trial carried out on 70 patients suffering from advanced cancer pain , evaluated the analgesic efficacy and side effects of this drug . The second , an open study of 113 patients , assessed analgesic efficacy , incidence of side effects , and the effects of age on dose . The analgesia provided by controlled-release morphine administration proved to be superimposable to those of the oral aqueous morphine solution . Moreover , the use of controlled-release morphine was associated with a statistically significant reduction of some side effects . Ninety-one percent of patients needed controlled-release morphine every 12 hr , while 9 % required it every 8 hr PURPOSE This study compared the clinical efficacy of oxycodone hydrochloride controlled-release ( CR ) tablets administered every 12 hours with immediate-release ( IR ) oxycodone tablets administered four times daily in patients with cancer-related pain . PATIENTS AND METHODS Cancer patients who required therapy for moderate to severe pain were r and omized to CR oxycodone every 12 hours ( n=81 ) or IR oxycodone four times daily ( n=83 ) for 5 days in a multicenter , double-blind study . Pain intensity was assessed four times daily ( categorical scale of none , slight , moderate , and severe ) ; acceptability of therapy was assessed twice daily ( categorical scale of very poor , poor , fair , good , and excellent ) . RESULTS Pain intensity remained slight during the study , with mean oxycodone doses of 114 mg/d ( range , 20 to 400 mg/d ) for CR and 127 mg/d ( range , 40 to 640 mg/d ) for IR . Acceptability of therapy was fair to good with both treatments . While st and ard conversion ratios provided an acceptable dose for many patients , a protocol amendment that allowed initial titration and use of rescue medication reduced the discontinuation rate for lack of acceptable pain control ( from 34 % to 4 % with CR and from 31 % to 19 % with IR before and after amendment , respectively ) without increasing the discontinuation rate for adverse events ( from 8 % to 7 % with CR and from 13 % to 11 % with IR ) . Fewer adverse events were reported with CR ( 109 ) than with IR ( 186 ) oxycodone ( P=.006 ) . CONCLUSION CR oxycodone every 12 hours was as effective as IR oxycodone four times daily in managing moderate to severe cancer-related pain and was associated with fewer reports of adverse events Seventy-five patients with moderate to severe cancer pain were r and omly assigned in a double-blind fashion to receive first-dose ketorolac tromethamine 10 mg orally , acetaminophen 600 mg plus codeine 60 mg orally , or placebo , followed by subsequent doses of ketorolac or acetaminophen plus codeine four times daily for 7 days . Patient characteristics were similar among the treatment groups . The first-dose observation documented that both ketorolac and acetaminophen plus codeine produced an equivalent reduction in cancer pain and were superior to placebo as measured by pain intensity differences and pain relief . Multidose comparison documented a small but statistically significant advantage in mean daily pain relief favoring acetaminophen plus codeine , although there were no differences in mean daily ratings of overall effects for either study medication . Adverse symptoms were acceptable with both ketorolac and acetaminophen plus codeine . We conclude that ketorolac has significant analgesic activity in patients with cancer pain , although its precise role in the treatment regimen of these patients remains undefined Twenty‐three adult patients with chronic pain due to cancer completed a double‐blind , r and omized , two‐phase crossover trial comparing plasma morphine concentrations and analgesic efficacy of oral morphine sulfate solution ( MSS ) and controlled‐release morphine sulfate tablets ( MS Contin [ MSC ] , Purdue Frederick , Inc. , Toronto , Ontario , Canada ) . MS Contin was given every 12 hours to all patients except those whose daily morphine dose could not be equally divided into two 12‐hour doses with the tablet strengths available . MSS was given every 4 hours . Patients received both of the test drugs for at least 5 days , and , on the final day of each phase , peripheral venous blood sample s for morphine analysis were obtained . Eighteen patients received MSC every 12 hours , and five received it every 8 hours . The same total daily morphine dose was given in both phases . In the 18 patients who received MSC every 12 hours , the daily morphine dose was 183.9 ± 140.0 mg ( mean ± SD ) . In this group , the mean area under the curve ( AUC ) with MSC was 443.6 ± 348.4 ng/ml/hour , compared with 406.8 ± 259.7 ng/ml/hour for MSS ( P > 0.20 ) . Mean maximum morphine concentrations ( Cmax ) for MSC and MSS were 67.9 ± 42.1 and 58.8 ± 30.3 ng/ml , respectively ( P > 0.05 ) . Mean minimum morphine concentrations ( Cmin ) were 17.0 ± 17.7 and 18.3 ± 15.0 , respectively ( P > 0.30 ) . There was a significant difference ( P < 0.001 ) between the two drugs in time required to reach maximum morphine concentration ( Tmsx ) . Mean Tmax after MSC occurred at 3.6 ± 2.3 hours . After MSS , it occurred at 1.3 ± 0.4 hours . In the five patients who received MSC every 8 hours , the findings paralleled those in the principal group , with no significant differences between MSC and MSS in Cmax or Cmin . and a highly significant difference between the two in Tmax . However , in this small group of patients , the AUC with MSC was significantly ( P = 0.04 ) greater than that with MSS . All patients had very good pain control throughout the study and both formulations were well tolerated . There were no significant differences between MSC and MSS in pain scores or side effects . Under the conditions of this study there was no clinical ly significant difference in bioavailability between MSC and oral MSS . When given on a 12‐hourly basis in individually titrated doses , the MSC provided therapeutic plasma morphine concentrations throughout the dosing interval Two separate trials compared controlled-release ( CR ) oral oxycodone ( administered every 12 hours ) with immediate-release ( IR ) oxycodone ( 4 times a day ) to determine whether patients with chronic pain could be titrated to stable pain control as readily with the CR as with the IR formulation . In one study , 48 patients with cancer pain were r and omized to open-label titration with either CR or IR oxycodone ( maximum dose , 400 mg/day ) for a period of up to 21 days . In a study of similar design , 57 patients with low back pain were titrated with either CR or IR oxycodone ( maximum dose , 80 mg/day ) for a period of up to 10 days . The majority of patients in both studies were converted to oxycodone from other opioid analgesics . Results of both studies showed no difference between CR and IR oxycodone with respect to both the percentage of patients achieving stable pain control , the time to achieve stable pain control , and the degree of pain control achieved . Among cancer patients , 85 % achieved stable analgesia , 92 % with the CR formulation and 79 % with the IR formulation . Among noncancer patients , 91 % achieved stable pain control , 87 % with the CR formulation and 96 % with the IR formulation . The most commonly reported adverse effects in both studies were similar for the two formulations and were those anticipated with opioids : nausea , vomiting , constipation , somnolence , dizziness , and pruritus . Nausea and vomiting were the most frequently cited reasons for treatment discontinuations . These studies suggest that dose titration can be accomplished as readily with oral CR oxycodone as with IR oxycodone in patients with chronic , moderate to severe pain Objective According to experimental findings , oxycodone ( OX ) could have some advantages over morphine ( MO ) in clinical models of visceral pain . It was hypothesized that OX could have some advantages over MO in terms of efficacy and dose escalation in pancreatic cancer pain . Methods Sixty patients with pancreatic cancer with a pain intensity rating of 4/10 who required opioids were included in the study . Patients were r and omized to receive 30 mg/d of sustained release oral MO or sustained release oral OX ( 20 mg/d ) . Opioid doses were increased according to the clinical needs . Daily doses of opioids , pain and symptom intensity were recorded at admission ( T0 ) and at weekly intervals for the subsequent 4 weeks ( T1 , T2 , T3 , and T4 ) , with an extension at 8 weeks ( T8 ) . Opioid escalation index ( OEI ) as percentage ( OEI % ) and in mg ( OEI mg ) was calculated . Results Nineteen and 20 patients in groups OX and MO , respectively , were followed for the entire period of study ( T4 ) . No differences between groups were found in age ( P=0.400 ) , Karnofsky ( P=0.667 ) , or escalation indexes at T4 and T8 ( OEImg , P=0.945 and OEI % , P=0.295 ) . No statistical differences in pain and symptoms intensity between the groups were observed . Conclusion OX and MO provided similar analgesia and adverse effects with similar escalating doses in patients with pancreatic cancer pain , resembling observations reported in the general cancer pain population . The experimental hypothesis that OX would be superior to MO in the clinical model of pancreatic cancer pain was not confirmed Oncology nursing is concerned with pain relief and overall Quality of Life ( QOL ) . The purpose of this study was to determine the effects of controlled-release morphine on QOL for patients with cancer . Eighty-three subjects were r and omly assigned in a clinical trial of short-acting versus controlled-release analgesia ( MS Contin , Purdue Frederick Co. , Norwalk , CT ) . Data was collected in a repeated measures design every 2 weeks for 6 weeks yielding a total of 240 visits . Five instruments were used to assess QOL , pain , and functional status . Study findings indicate improved pain management with controlled-release MS Contin and important nursing implication s for the management of analgesia-induced gastrointestinal symptoms . Through appropriate pain management with pain therapies such as controlled-release analgesia , nurses can greatly enhance QOL for the patient with cancer CONTEXT Recently , a new oral prolonged-release formulation of morphine sulfate for once-daily dosing has been developed based on an injection-molded matrix ( abuse-deterrent , prolonged-release erodible matrix [ ADPREM ] ) . OBJECTIVES The objective of this double-blind , r and omized , exploratory crossover study was to assess the efficacy and safety of once-daily ADPREM compared with twice-daily controlled-release morphine ( CRM ; MST ContinusNapp Pharmaceuticals , Cambridge , UK ) . METHODS Thirty-eight adult cancer pain patients participated in the study , which consisted of a run-in period for stabilization and two consecutive fixed-dose treatment periods of two weeks ' duration each . Rescue medication , immediate-release morphine sulfate , was available during the entire study for treatment of breakthrough pain ( BTP ) . RESULTS There was no difference between the treatments in use of rescue medication . The medians of the average number of rescue doses per day were 1.0 and 0.7 during the ADPREM and CRM treatment periods , respectively , with an estimated median difference of 0.07 dose/day ( 95 % confidence interval : -0.21 , 0.29 ) . Likewise , no differences between treatments were found for the number of BTP episodes per day or morning and evening ratings of pain intensity ( current , average , minimum , and maximum ) . Median assessment of the drugs was " good " for both treatments , and neither of the treatments was preferred . Steady-state trough concentrations of morphine and its metabolites in plasma before morning dosing were similar after either treatment period . The adverse events were as expected in an opioid-treated cancer population and showed no differences between ADPREM and CRM . CONCLUSION In this study , dosing with ADPREM at intervals of 24 hours was therapeutically equivalent to CRM dosed at intervals of 12 hours Abstract Healthy university students and hospital staff taking no medications were surveyed by question naire to obtain data on the occurrence of many symptoms often listed as side effects of drugs Abstract R and omised controlled trials ( RCTs ) alone are unlikely to provide reliable estimates of the incidence of rare events because of their limited size . Cohort , case control , and other observational studies have large numbers but are vulnerable to various kinds of bias . Wanting to estimate the risk of death from bleeding or perforated gastroduodenal ulcers with chronic usage of non‐steroidal anti‐inflammatory drugs ( NSAIDs ) with greater precision , we developed a model to quantify the frequency of rare adverse events which follow a biological progression . The model combined data from both RCTs and observational studies . We search ed systematic ally for any report of chronic ( ≥2 months ) use of NSAIDs which gave information on gastroduodenal ulcer , bleed or perforation , death due to these complications , or progression from one level of harm to the next . Fifteen RCTs ( 19 364 patients exposed to NSAIDs for 2–60 months ) , three cohort studies ( 215 076 patients redeeming a NSAID prescription over a 3–12 month period ) , six case‐control studies ( 2957 cases ) and 20 case series ( 7406 ) , and case reports ( 4447 ) were analysed . In RCTs the incidence of bleeding or perforation in 6822 patients exposed to NSAIDs was 0.69 % ; two deaths occurred . Of 11 040 patients with bleeding or perforation with or without NSAID exposure across all reports , 6–16 % ( average 12 % ) died ; the risk was lowest in RCTs and highest in case reports . Death from bleeding or perforation in all controls not exposed to NSAIDs occurred in 18 out of 849 489 ( 0.002 % ) . From these numbers we calculated the number‐needed‐to‐treat for one patient to die due to gastroduodenal complications with chronic ( ≥2 months ) NSAIDs as 1/((0.69 × {6–16 % , average 12%})−0.002%))=909–2500 ( average 1220 ) . On average 1 in 1200 patients taking NSAIDs for at least 2 months will die from gastroduodenal complications who would not have died had they not taken NSAIDs . This extrapolates to about 2000 deaths each year in the UK The role of opioids for moderate pain ( so-called " weak " opioids ) in the second step of the World Health Organization 's analgesic ladder has been investigated in a prospect i ve r and omized study . Sixteen patients were administered dextropropoxyphene ( DPP ) in a dosage ranging from 120 mg to 240 mg daily ( group 1 ) , and 16 patients were administered the lowest doses ( 20 mg daily ) of commercially available controlled-release morphine ( group 2 ) . Equianalgesic doses of oral morphine , pain relief , and symptoms during the first 10 days of therapy and during the last 4 weeks before death were assessed . Three of 16 patients maintained DPP until death , whereas three patients in group 2 were switched to DPP due to the occurrence of intolerable side effects . Intensity and frequency of nausea and vomiting , drowsiness , and dry mouth were higher in group 2 than in group 1 during the initial treatment . These results stress the role of " weak " opioids during the induction of opioid therapy in opioid-naive cancer patients Nineteen patients with pain from advanced cancer stabilised on oral 4‐hourly aqueous morphine who were to be converted to twice daily controlled‐release morphine tablets ( MST Continus ) completed this study . Patients were r and omised to receive either their usual 4‐hourly morphine dose or placebo with the first dose of MST tablets . There were no significant differences between the treatment groups in ratings of pain intensity , pain relief or side effects , or in any of the measured pharmacokinetic parameters . No patients in the placebo group experienced any breakthrough pain , and nursing staff were unable to identify which patients had received the active dose of morphine elixir . We conclude that there is no need for a loading dose when aqueous morphine is changed to MST tablets Abstract Objective : This phase 3 study evaluated the efficacy and safety of tapentadol extended release ( ER ) compared with oxycodone controlled release ( CR ) for the management of moderate to severe , chronic malignant tumor-related cancer pain . Research design and methods : This r and omized , double-blind , active-controlled study included Japanese and Korean patients with moderate to severe , chronic malignant tumor-related pain . Patients were r and omized ( 1:1 ) to receive oral tapentadol ER ( 25–200 mg bid ) or oral oxycodone HCl CR ( 5–40 mg bid ) for 4 weeks of double-blind treatment . Clinical Trials.gov identifier : Clinical Trials.gov identifier : NCT01165281 . Main outcome measures : This study was design ed to evaluate the non-inferiority of the efficacy provided by tapentadol ER versus oxycodone CR , based on the mean change in average pain intensity ( 11 point numerical rating scale ) from baseline to the last 3 days of study drug administration . Treatment-emergent adverse events ( TEAEs ) were recorded throughout the study . Results : Of the 374 patients who were screened , 343 were r and omized and 236 completed treatment . The least-squares mean difference in the change in pain intensity from baseline to the last 3 days of study treatment between tapentadol ER and oxycodone CR was −0.06 ( 95 % confidence interval [ CI ] , −0.506 to 0.383 ) . The upper limit of the 95 % CI was < 1 ( the predefined threshold value for non-inferiority ) , indicating that tapentadol ER provided analgesic efficacy that was non-inferior to that of oxycodone CR . The percentage of patients reporting at least one TEAE was similar in the tapentadol ER ( 87.5 % [ 147/168 ] ) and oxycodone CR ( 90.1 % [ 155/172 ] ) treatment groups , but the incidence of gastrointestinal TEAEs was lower in the tapentadol ER group ( 55.4 % [ 93/168 ] ) than in the oxycodone CR group ( 67.4 % [ 116/172 ] ) . Conclusions : Tapentadol ER ( 25–200 mg bid ) provides analgesic efficacy that is non-inferior to that provided by oxycodone HCl CR ( 5–40 mg bid ) for the management of moderate to severe , chronic malignant tumor-related pain , and is well tolerated overall , with a better gastrointestinal tolerability profile than oxycodone CR The relative analgesic potency of single grade d intramuscular doses of oxycodone and morphine was evaluated in a double-blind study in patients with chronic pain due to cancer . When both intensity and duration of analgesia are considered ( total analgesic effect ) , oxycodone was 2/3 to 3/4 as potent as morphine , while in terms of peak analgesia , it was 8/10 to equipotent . In doses producing equivalent peak effect , oxycodone had a shorter duration of action than morphine . Intramuscular oxycodone was also compared to intramuscular codeine in a similar patient group . In terms of total analgesic effect , oxycodone was 10 times as potent as codeine , while in terms of peak analgesia it was 12 times as potent . These relative potency relationships of oxycodone , taken in conjunction with the oral/parenteral potency ratios of codeine and oxycodone established in the previous paper and several previous relative potency assays involving morphine , oxymorphone and codeine , demonstrate a highly consistent pattern of analgesic structure-activity relationships encompassing morphine , oxymorphone , codeine and oxycodone . The results of these studies do not appear to support the hypothesis that , in man , the analgesic activity of codeine is due to its O-demethylation to morphine |
12,977 | 23,076,918 | The potential benefit of antibiotics in the treatment of clinical ly diagnosed acute rhinosinusitis needs to be seen in the context of a high prevalence of adverse events .
Taking into account antibiotic resistance and the very low incidence of serious complications , we conclude that there is no place for antibiotics for the patient with clinical ly diagnosed , uncomplicated acute rhinosinusitis . | BACKGROUND In primary care setting s , the diagnosis of rhinosinusitis is generally based on clinical signs and symptoms .
Technical investigations are not routinely performed , nor recommended .
Individual trials show a trend in favour of antibiotics , but the balance of benefit versus harm is unclear . | CONTEXT Evidence to support antibiotic treatment for acute rhinosinusitis is limited , yet antibiotics are commonly used . OBJECTIVE To determine the incremental effect of amoxicillin treatment over symptomatic treatments for adults with clinical ly diagnosed acute rhinosinusitis . DESIGN , SETTING , AND PARTICIPANTS A r and omized , placebo-controlled trial of adults with uncomplicated , acute rhinosinusitis were recruited from 10 community practice s in Missouri between November 1 , 2006 , and May 1 , 2009 . INTERVENTIONS Ten-day course of either amoxicillin ( 1500 mg/d ) or placebo administered in 3 doses per day . All patients received a 5- to 7-day supply of symptomatic treatments for pain , fever , cough , and nasal congestion to use as needed . MAIN OUTCOME MEASURES The primary outcome was improvement in disease-specific quality of life after 3 to 4 days of treatment assessed with the Sinonasal Outcome Test-16 ( minimally important difference of 0.5 units on a 0 - 3 scale ) . Secondary outcomes included the patient 's retrospective assessment of change in sinus symptoms and functional status , recurrence or relapse , and satisfaction with and adverse effects of treatment . Outcomes were assessed by telephone interview at days 3 , 7 , 10 , and 28 . RESULTS A total of 166 adults ( 36 % male ; 78 % with white race ) were r and omized to amoxicillin ( n = 85 ) or placebo ( n = 81 ) ; 92 % concurrently used 1 or more symptomatic treatments ( 94 % for amoxicillin group vs 90 % for control group ; P = .34 ) . The mean change in Sinonasal Outcome Test-16 scores was not significantly different between groups on day 3 ( decrease of 0.59 in the amoxicillin group and 0.54 in the control group ; mean difference between groups of 0.03 [ 95 % CI , -0.12 to 0.19 ] ) and on day 10 ( mean difference between groups of 0.01 [ 95 % CI , -0.13 to 0.15 ] ) , but differed at day 7 favoring amoxicillin ( mean difference between groups of 0.19 [ 95 % CI , 0.024 to 0.35 ] ) . There was no statistically significant difference in reported symptom improvement at day 3 ( 37 % for amoxicillin group vs 34 % for control group ; P = .67 ) or at day 10 ( 78 % vs 80 % , respectively ; P = .71 ) , whereas at day 7 more participants treated with amoxicillin reported symptom improvement ( 74 % vs 56 % , respectively ; P = .02 ) . No between-group differences were found for any other secondary outcomes . No serious adverse events occurred . CONCLUSION Among patients with acute rhinosinusitis , a 10-day course of amoxicillin compared with placebo did not reduce symptoms at day 3 of treatment . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00377403 In this double-blind , parallel-group , multicenter study , 169 patients with symptoms of maxillary sinusitis but without radiographically confirmed empyema ( pus ) were r and omly assigned to receive either 500 mg azithromycin once daily for 3 days ( 87 patients ) or placebo daily for 3 days ( 82 patients ) . Nasal secretion , maxillary tenderness and pain , nasal obstruction , general malaise , and hyposmia were assessed at the start of the study and on days 4 , 11 , and 25 of treatment . After 11 days 58 % of the patients in the azithromycin group were cured versus 31 % in the placebo group ; after 25 days the cure rate was 79 % versus 67 % , respectively . When both cure and improvement were considered , the corresponding figures after day 25 were 90 % and 88 % , respectively . Adverse events , predominantly gastrointestinal , occurred in 24 ( 27 % ) of the azithromycin-treated patients and in 15 ( 18 % ) of those treated with placebo , but the difference was not statistically significant . There was a difference in efficacy in favor of azithromycin in the treatment of rhinitis with symptoms of maxillary sinusitis but without radiological signs of empyema ( pus ) . Antibiotics should only be used to alleviate symptoms in patients with moderate to severe symptoms , as the results after 25 days for both improvement and cure are equal . In the treatment of acute rhinitis with symptoms and signs of maxillary sinusitis but without empyema , treatment with azithromycin seems to result in a better cure rate after 10–12 days when compared with placebo OBJECTIVE To compare the efficacy of amoxicillin vs placebo in patients with an acute upper respiratory tract infection and purulent rhinorrhea . STUDY DESIGN Double-blind r and omized placebo-controlled trial . POPULATION The 416 patients included from 69 family practice s were 12 years or older , presenting with acute upper respiratory complaints , and having a history of purulent rhinorrhea and no signs of complications of sinusitis . OUTCOMES MEASURED Therapy success ( disappearance of symptoms that most greatly affected the patient 's health ) at day 10 and duration of general illness , pain , and purulent rhinorrhea . RESULTS Therapy was successful in 35 % of patients with amoxicillin and in 29 % of patients with placebo ( relative risk [ RR ] 1.14 , 95 % confidence interval [ CI ] , 0.92 - 1.42 ) . There was no effect on duration of general illness or pain . Duration of purulent rhinorrhea was shortened by amoxicillin ( 9 days vs 14 for clearing of purulent rhinorrhea in 75 % of patients ; P = .007 ) . Diarrhea was more frequent with amoxicillin ( 29 % vs 19 % , RR 1.28 , 95 % CI , 1.05 - 1.57 ) . No complications were reported . One patient ( 0.5 % ) receiving amoxicillin and 7 ( 3.4 % ) receiving placebo discontinued trial therapy because of exacerbation of symptoms ( RR 0.25 , 95 % CI 0.04 - 1.56 , P = .07 ) . All 8 patients recovered with antibiotic therapy . CONCLUSIONS Amoxicillin has a beneficial effect on purulent rhinorrhea caused by an acute infection of the nose or sinuses but not on general recovery . The practical implication is that all such patients , whatever the suspected diagnosis , can be safely treated with symptomatic therapy and instructed to return if symptoms worsen CONTEXT Acute sinusitis is a common clinical problem that usually results in a prescription for antibiotics but the role of antibiotics is debated . Anti-inflammatory drugs such as topical steroids may be beneficial but are under research ed . OBJECTIVE To determine the effectiveness of amoxicillin and topical budesonide in acute maxillary sinusitis . DESIGN , SETTING , AND PATIENTS A double-blind , r and omized , placebo-controlled factorial trial of 240 adults ( aged > or = 16 years ) with acute nonrecurrent sinusitis ( had > or = 2 diagnostic criteria : purulent rhinorrhea with unilateral predominance , local pain with unilateral predominance , purulent rhinorrhea bilateral , presence of pus in the nasal cavity ) at 58 family practice s ( 74 family physicians ) between November 2001 and November 2005 . Patients were r and omized to 1 of 4 treatment groups : antibiotic and nasal steroid ; placebo antibiotic and nasal steroid ; antibiotic and placebo nasal steroid ; placebo antibiotic and placebo nasal steroid . INTERVENTION A dose of 500 mg of amoxicillin 3 times per day for 7 days and 200 mug of budesonide in each nostril once per day for 10 days . MAIN OUTCOME MEASURES Proportion clinical ly cured at day 10 using patient symptom diaries and the duration and severity of symptoms . RESULTS The proportions of patients with symptoms lasting 10 or more days were 29 of 100 ( 29 % ) for amoxicillin vs 36 of 107 ( 33.6 % ) for no amoxicillin ( adjusted odds ratio , 0.99 ; 95 % confidence interval , 0.57 - 1.73 ) . The proportions of patients with symptoms lasting 10 or more days were 32 of 102 ( 31.4 % ) for topical budesonide vs 33 of 105 ( 31.4 % ) for no budesonide ( adjusted odds ratio , 0.93 ; 95 % confidence interval , 0.54 - 1.62 ) . Secondary analysis suggested that nasal steroids were significantly more effective in patients with less severe symptoms at baseline . CONCLUSION Neither an antibiotic nor a topical steroid alone or in combination was effective as a treatment for acute sinusitis in the primary care setting . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N60825437 BACKGROUND Sinusitis is the fifth most common reason for patients to visit primary care physicians , yet clinical outcomes relevant to patients are seldom studied . OBJECTIVE To determine whether patients with purulent rhinitis , " sinusitis-type symptoms , " improved with antibiotics . Second , to examine a clinical prediction rule to provide preliminary validation data . METHODS Prospect i ve clinical trial , with double-blinded placebo controlled r and omization . The setting was a suburb of Washington , DC , from Oct 1 , 2001 , to March 31 , 2003 . All participants were 18 years or older , presenting to a family practice clinic with a complaint of sinusitis and with pus in the nasal cavity , facial pressure , or nasal discharge lasting longer than 7 days . The main outcome measures were resolution of symptoms within a 14-day follow-up period and the time to improvement ( days ) . RESULTS After exclusion criteria , 135 patients were r and omized to either placebo ( n=68 ) or amoxicillin ( n=67 ) for 10 days . Intention-to-treat analyses showed that 32 ( 48 % ) of the amoxicillin group vs 25 ( 37 % ) of the placebo group ( P=.26 ) showed complete improvement by the end of the 2-week follow-up period ( relative risk=1.3 ; 95 % confidence interval [ CI ] , 0.87 - 1.94 ] ) . Although the rates of improvement were not statistically significantly different at the end of 2 weeks , the amoxicillin group improved significantly earlier , in the course of treatment , a median of 8 vs 12 days , than did the placebo group ( P=.039 ) . CONCLUSION For most patients with sinusitis-type complaints , no improvement was seen with anti-biotics over placebo . For those who did improve , data suggested there is a subgroup of patients who may benefit from antibiotics Objective . Although antimicrobial treatment for children with acute sinusitis is used commonly , it is unclear whether it offers significant clinical benefit . The purpose of this study was to evaluate the effectiveness of antimicrobial treatments for acute sinusitis as they are used in community pediatric practice . Methods . We conducted a r and omized , placebo-controlled trial in 3 community pediatric practice s in St Louis , Missouri . A total of 188 patients who were between the ages of 1 and 18 years and who had had 10 to 28 days of persistent sinus symptoms and a clinical diagnosis of acute sinusitis were r and omized to receive 14 days of amoxicillin ( 40 mg/kg/d in 3 daily doses ) , amoxicillin-clavulanate ( amoxicillin 45 mg/kg/d in 2 daily doses ) , or placebo . Change in sinus symptoms was assessed both by a quantitative symptom score ( the S5 score ) and subjectively by the parent . Secondary outcomes included adverse effects of treatment and recurrence or relapse of sinus symptoms . Outcomes were assessed by telephone interviews over a 2-month period . Results . Of the 161 patients who were included in the analysis , 58 received amoxicillin , 48 received amoxicillin-clavulanate , and 55 received placebo . Day 14 improvement rates were 79 % , 81 % , and 79 % , respectively . There were no differences in the 14-day change in S5 score among treatment groups . The rates of adverse events ( amoxicillin , 19 % ; amoxicillin-clavulanate , 11 % ; placebo , 10 % ) , relapse ( amoxicillin , 12 % ; amoxicillin-clavulanate , 13 % ; placebo , 13 % ) , and recurrence ( amoxicillin , 9 % ; amoxicillin-clavulanate , 13 % ; placebo , 13 % ) of sinus symptoms were similar among treatment groups . Conclusion . Neither amoxicillin nor amoxicillin-clavulanate offered any clinical benefit compared with placebo for children with clinical ly diagnosed acute sinusitis Summary In 50 adults with bacterial sinusitis , cyclacillin ( 1500 mg . per day for 7 days ) proved significantly more effective than placebo in eliminating the signs and symptoms and in eradicating the causative microorganisms , ( Staphylococcus aureus , Proteus mirabilis , and Staph , epidermidis were most frequently isolated in this series ) . Sixty percent of the cultures in the cyclacillin series were sterilized , compared with only 10 % in the placebo series . Globally , 93 % of the cyclacillin-treated patients and only 55 % of the placebo-treated patients were considered improved . Of the P. mirabilis strains encountered , 72 % were eradicated by cyclacillin ( only 40 % by placebo ) despite the relatively high cyclacillin M.I.C.s for this microorganism ( 50 to 100 μg/ml . ) . Cyclacillin was much more effective in treating human sinusitis than would have been anticipated from the M.I.C.s alone Sc and J Prim Health Care 2003;21:00 - 00 . ISSN 0281 - 34323 Objectives r - r To compare antibiotics and placebo in patients with clinical ly diagnosed acute maxillary sinusitis ( AMS ) . To study whether sinus ultrasound examination would help to detect those patients who benefit from antibiotic therapy . Design r - r A double-blind , r and omised , placebo-controlled multicentre trial . Setting r - r Nine primary care sites in Finl and . Subjects r - r 150 adult patients ( mean age 39.7 years ) with a clinical diagnosis of sinusitis . Intervention r - r Antibiotics ( amoxicillin 750 mg 2 2 , doxycycline 100 mg 2 2 or penicillin V 1500 mg 2 2 ) or placebo twice daily for 7 days ; all patients were examined with sinus ultrasound after r and omisation . Main outcome measure r - r Clinical success ( patients ' report of recovery ) in telephone interview at 2 weeks . Results r - r A total of 146 patients completed the 2-week follow-up . Patients receiving antibiotics achieved a slightly higher rate of clinical success than patients receiving placebo ( 80 % vs 66 % ; p=0.068 ) . Conclusions r - r Antibiotics hasten symptom relief in AMS . Yet many patients recover in 2 weeks without antimicrobial treatment . Only half of patients with a clinical diagnosis of AMS have sinusitis in ultrasound examination Abstract Objective : To compare the effectiveness of penicillin V and amoxycillin with placebo in treatment of adult patients with acute sinusitis . Design : R and omised , double blind , placebo controlled trial . Setting : Norwegian general practice . Subjects : 130 adult patients with a clinical diagnosis of acute sinusitis confirmed by computed tomography . Main outcome measures : Subjective status after three and 10 days of treatment , difference in clinical severity score between day 0 and day 10 as evaluated by the general practitioner , difference in score from computed tomography on day 0 and day 10 , and duration of sinusitis . Results : Amoxycillin and penicillin V led to significantly faster and better recovery than placebo . By day 10 , 71 patients receiving antibiotic treatment ( 86 % ) considered themselves to be recovered or much better compared with 25 ( 57 % ) receiving placebo . The mean ( 95 % confidence interval ) reductions in clinical severity scores by day 10 were 5.4 ( 5.0 to 5.8 ) for penicillin V , 5.5 ( 4.9 to 6.0 ) for amoxycillin , and 3.4 ( 2.8 to 4.0 ) for placebo . For the antibiotic groups combined the number of patients with the greatest degree of improvement on computed tomography ( scale 0 - 16)—that is , score 5 - 16 on day 10—was 31/83 ( 37 % ) compared with 10/44 ( 23 % ) receiving placebo . The median duration of the sinusitis was nine days in the amoxycillin group , 11 days in the penicillin V group , and 17 days in the placebo group . Conclusion : Penicillin V and amoxycillin are significantly more effective than placebo in the treatment of acute sinusitis . Key messages The median duration of sinusitis with different treatment was nine days for amoxycillin , 11 days for penicillin V , and 17 days for placebo More than half of the patients receiving antibiotic treatment reported side effects but few gave severe discomfort Half of the patients receiving placebo tablets felt restored or much better after 10 BACKGROUND Acute rhinosinusitis is one of the most common reasons for prescribing antibiotics in primary care . However , it is not clear whether antibiotics improve the outcome for patients with clinical ly diagnosed acute rhinosinusitis . We evaluated the effect of a combination product of amoxicillin-potassium clavulanate on adults with acute rhinosinusitis that was clinical ly diagnosed in a general practice setting . METHODS We conducted a r and omized , placebo-controlled , double-blind trial with 252 adults recruited at 24 general practice s and 2 outpatient clinics . Each patient had a history of purulent nasal discharge and maxillary or frontal pain for at least 48 hours . Patients were given amoxicillin , 875 mg , and clavulanic acid , 125 mg , or placebo twice daily for 6 days . Main outcome measures were time to cure ( primary outcome ) , number of days during which rhinosinusitis restricted activities at home or work , and frequency of adverse effects ( secondary outcomes ) . RESULTS The adjusted hazard ratio for the effect of amoxicillin-clavulanate was 0.99 ( 95 % confidence interval [ CI ] , 0.68 - 1.45 ) on time to cure and 1.28 ( 95 % CI , 0.80 - 2.05 ) in the prespecified subgroup of patients with a positive rhinoscopy result . At 7 days the mean difference between amoxicillin-clavulanate and placebo was -0.29 ( 95 % CI , -0.93 to 0.34 ) in the number of days with restrictions due to rhinosinusitis and -0.60 ( 95 % CI , -1.41 to 0.21 ) in patients with a positive rhinoscopy result . At 7 days patients who took amoxicillin-clavulanate were more likely to have diarrhea ( odds ratio , 3.89 ; 95 % CI , 2.09 - 7.25 ) . CONCLUSIONS Adult patients in general practice with clinical ly diagnosed acute rhinosinusitis experience no advantage with antibiotic treatment with amoxicillin-clavulanate and are more likely to experience adverse effects Aim : To evaluate the efficacy of antibiotic treatment in children who presented in medical care with respiratory infection and had imaging evidence of sinusitis . Methods : Eighty‐two children ( 4–10 y ) with acute respiratory symptoms and ultrasonography findings suggestive of acute rhinosinusitis were enrolled in a r and omized , double‐blind trial . The sinus findings were confirmed with plain radiographs . The children received either cefuroxime axetil in 125‐mg capsules twice a day for 10 d or placebo . Main outcome measures were complete cure in 2 wk and absence of prolonged symptoms or complications . Results : A total of 72 children ( 88 % ) completed follow‐up . The sinusitis findings in the ultrasound could be confirmed with plain radiographs in 65 of the 72 patients ( 90 % ) . The proportion of children completely cured by day 14 was similar in both groups ( difference 6 % , 95 % confidence interval −16 % to 29 % ) . Similarly , there was no significant difference in the proportions of children who escaped prolonged disease and complications between the groups ( difference 7 % , −9 % to 24 % ) We compared the efficacy of penicillin V and amoxycillin treatment with placebo in 70 adult patients from Norwegian family practice with a clinical diagnosis of acute sinusitis and mucosal thickening on CT , but without fluid level or total opacification . The study was r and omized and double-blind . Three different outcomes were evaluated ; subjective status after 10 days of treatment , difference in clinical score between day 0 and day 10 , and duration of the illness episode . Amoxycillin and penicillin V gave no better response to treatment than placebo , evaluated by all three outcome measures . The median duration of the sinusitis episode was 10 days in the amoxycillin- and placebo groups and 13 days in the penicillin-V group . In patients with a clinical diagnosis of acute sinusitis , fluid level and total opacification on CT are good criteria to differentiate between groups of patients that need or do not need antibiotic treatment A minority of patients with upper respiratory tract infections ( URTI ) have a bacterial infection and may benefit from antibiotherapy . In previous investigations we showed that in patients suffering from acute rhinosinusitis associated with the presence of Streptococcus pneumoniae , Haemophilus influenzae or Moraxella catarrhalis in their nasopharygeal secretions , resolution of symptoms was significantly improved by antibiotic treatment . The present analysis was performed to determine whether specific clinical symptoms or signs observed during careful endoscopic examination of the nasal cavities could help the clinician to identify a subset of patients with moderate forms of acute rhinosinusitis infected with pathogenic bacteria . Detailed clinical histories were obtained and medical examinations performed in 265 patients ( 138 females , 127 males ; mean age 35 years ) presenting with a < 4-week history of URTI symptoms but who did not require immediate antibiotic therapy for severe rhinosinusitis . The presence of three pathogenic bacteria ( S. pneumoniae , H. influenzae and M. catarrhalis ) was determined in all patients by culture of nasopharyngeal secretions . Azithromycin ( 500 mg day for 3 days ; n = 133 ) or placebo ( n = 132 ) were r and omly given to all patients in a double-blind manner . Pathogenic bacteria were found in 77 patients ( 29 % ) . The clinical signs and symptoms significantly associated in a multivariate model with the presence of bacteria included colored nasal discharge ( p < 0.003 ) , facial pain ( p < 0.032 ) and radiologically determined maxillary sinusitis ( complete opacity , air-fluid level or mucosal thickening>10 mm ) ( p < 0.001 ) . This best predictive model had a sensitivity of 69 % and a specificity of 64 % and therefore could not be used either as a screening tool or as a diagnostic criterion for bacterial rhinosinusitis . In the group of patients with positive bacterial cultures , resolution of symptoms at Day 7 was observed in 73 % of patients treated with azithromycin and in 47 % of patients in the placebo group ( p < 0.007 ) . We conclude that signs and symptoms of acute rhinosinusitis in patients with mild-to-moderate clinical presentations are poor predictors of the presence of bacteria Abstract The aim of the present study was to assess the hypothesis that , when present in nasopharyngeal secretions , Streptococcus pneumoniae , Haemophilus influenzae , and Moraxella catarrhalis play a pathogenic role early in the course of an upper respiratory tract infection . Adults with a clinical diagnosis of acute sinusitis or common cold were enrolled . Participants were r and omly assigned in a double-blind manner to receive azithromycin 500 mg daily or placebo for 3 days . The effect of treatment on symptom evolution in the predefined subset of patients with Streptococcus pneumoniae , Haemophilus influenzae , or Moraxella catarrhalis in their nasopharyngeal secretions was assessed . Of 265 patients enrolled , 132 received placebo and 133 azithromycin . Streptococcus pneumoniae , Haemophilus influenzae , or Moraxella catarrhalis was identified in nasopharyngeal secretions of 77 patients ( 29 % ) . In this predefined subgroup of patients with Streptococcus pneumoniae , Haemophilus influenzae , or Moraxella catarrhalis , resolution of symptoms by day 7 occurred in 73 % of those treated with azithromycin compared with 47 % of those who received placebo ( P=0.007 ) . The median time before resolution of symptoms was 5 days in the azithromycin group compared to 7 days in the placebo group . Respiratory complications requiring antibiotic treatment occurred in 19 % of patients in the placebo group and in 3 % of the azithromycin group ( P=0.025 ) . In the remaining 188 patients without Streptococcus pneumoniae , Haemophilus influenzae , or Moraxella catarrhalis , resolution of symptoms by day 7 was similar in both groups ( 69 % in the placebo group vs. 64 % in the azithromycin group [ P=0.75 ] ) . Antibiotic treatment is of clinical benefit for patients with acute sinusitis or common cold when Streptococcus pneumoniae , Haemophilus influenzae , or Moraxella catarrhalis is present in nasopharyngeal secretions . This observation provides new insights into the pathogenic role of these bacteria in the early stage of the common cold BACKGROUND Acute sinusitis-like complaints are very common and are usually treated with antibiotics in spite of the lack of evidence for the effectiveness of antibiotic therapy and the increasing number of resistant strains . AIM To assess the effectiveness of doxycycline in adults with acute sinusitis-like complaints in general practice . METHOD The effects of doxycycline in a placebo-controlled , double-blind , r and omized trial were assessed in adults consulting their general practitioner ( GP ) with complaints after a common cold or influenza , pain in the head when bending forward , purulent nasal discharge , predominantly unilateral maxillary pain , toothache , or pain when chewing . Primary outcome events were the resolution of facial pain and the resumption of daily activities . Treatment differences were assessed by means of Kaplan-Meier curves and hazard ratios . The follow-up period was 42 days . RESULTS No significant difference was found in time to recover between the doxycycline-treated group and the placebo-treated group . However , the adjusted hazard ratio for the group receiving doxycycline was 1.17 ( 95 % CI = 0.87 - 1.57 ) for the resolution of pain and 1.31 ( 95 % CI = 0.96 - 1.78 ) for the resumption of daily activities . After 10 days , 85 % of all patients reported improvement and 60 % were completely cured . Side effects were reported by 17 % of the doxycycline-treated group , with two patients withdrawing because of side effects . CONCLUSIONS Data from this study indicate that doxycycline does not add to the effectiveness of decongestive nose drops and steam inhalation in treating acute sinusitis-like complaints in general practice adults OBJECTIVES To evaluate the efficacy and safety of moxifloxacin in the treatment of acute bacterial rhinosinusitis ( ABRS ) . STUDY DESIGN Prospect i ve , multicenter , r and omized , double-blind , phase III trial . METHODS Patients with ABRS defined by clinical , radiologic , and bacteriologic criteria were recruited to the study . Study treatments were 400 mg of oral moxifloxacin or a matching placebo daily for 5 days . The primary end point was clinical response at test-of-cure , 1 to 3 days after the end of therapy in the modified intent-to-treat ( mITT ) population ( patients with positive culture for one of five prespecified pathogens ) . Secondary efficacy variables included patient-reported symptom improvement measured using the Sino-Nasal Outcome Test-16 ( SNOT-16 ) , and concomitant medication use . RESULTS The mITT population consisted of 118 patients ( moxifloxacin , n = 73 ; placebo , n = 45 ) . Clinical success rates were numerically higher for moxifloxacin ( 78.1 % , 57/73 ) versus placebo ( 66.7 % , 30/45 ) ; ( P = .189 ) . Significantly greater mean reductions in SNOT-16 scores occurred in moxifloxacin- versus placebo-treated patients ( -17.54 vs. -12.83 ; P = .032 ) . Overall concomitant medication use was lower in moxifloxacin versus placebo patients ( 38.4 % , 28/73 vs. 55.6 % , 25/45 respectively ) . Premature discontinuation due to insufficient therapeutic effect was significantly lower in moxifloxacin- versus placebo-treated patients ( 8.2 % , 6/73 vs. 22.2 % , 10/45 ; P = .031 ) . The rate of treatment-emergent adverse events in the ITT population was similar between arms ( moxifloxacin 38.2 % , 96/251 ; placebo 40.7 % , 50/123 ) . CONCLUSIONS Although moxifloxacin 5-day therapy for ABRS was not statistically superior to placebo for the primary end point , patients who received moxifloxacin had significantly greater improvements in health outcomes and used fewer concomitant medicines than patients treated with placebo , while experiencing no increase in adverse events This study compared the relative effectiveness of two antimicrobial preparations , amoxicillin and amoxicillin-clavulanate potassium ( Augmentin ) , in the treatment of acute maxillary sinusitis in children 2 to 16 years of age . Of 171 children with persistent ( ten to 30 days ' duration ) nasal discharge or daytime cough or both , 136 ( 80 % ) had abnormal maxillary sinus radiographs . These children were stratified by age and severity of symptoms and r and omly assigned to receive either amoxicillin , amoxicillin-clavulanate potassium , or placebo . After the exclusion of 28 children with throat cultures positive for group A Streptococcus and 15 who did not complete their medication , the remaining 93 children were evaluated : 30 received amoxicillin , 28 received amoxicillin-clavulanate potassium , and 35 received placebo . Clinical assessment was performed at three and ten days . On each occasion , children treated with an antibiotic were more likely to be cured than children receiving placebo ( P less than .01 at three days , P less than .05 at ten days ) . The overall cure rate was 67 % for amoxicillin , 64 % for amoxicillin-clavulanate potassium , and 43 % for placebo INTRODUCTION The aim of the study was to compare the effectiveness of penicillin V with placebo in the treatment of adult patients with acute maxillary sinusitis ( in general practice ) . MATERIAL AND METHODS The study was design ed as a r and omised , double-blind , placebo-controlled trial in 26 Danish general practice s. The participants were 133 adult patients with acute maxillary sinusitis clinical ly diagnosed on maxillary pain and raised values of either C-reactive protein ( CRP ) or the erythrocyte sedimentation ( ESR ) rate . Main outcome measures were pain score and illness score , and CRP and ESR values after initiation of treatment . RESULTS Penicillin V led to a better recovery than placebo . The difference in pain reduction was statistically significant three days after initiation of treatment , whereas no significant difference was found in the reduction in the sense of illness . At the end of the study , significantly more patients in the penicillin group were completely free of pain than in the placebo group . This difference was found only in patients with an initial pain score of more than three . The cure rate was 71 % in the penicillin group and 37 % in the placebo group . Significantly more patients treated with penicillin achieved normal CRP values than those receiving placebo , respectively 88 % and 75 % . CONCLUSION Penicillin V is more effective than placebo in the treatment of acute maxillary sinusitis in adults in general practice , but only in patients with pronounced pain BACKGROUND The value of antibiotics in acute rhinosinusitis is uncertain . Although maxillary sinusitis is commonly diagnosed and treated in general practice , no effectiveness studies have been done on unselected primary -care patients . We used a r and omised , placebo-controlled design to test the hypothesis that there would be an improvement associated with amoxycillin treatment for acute maxillary sinusitis patients presenting to general practice . METHODS Adult patients with suspected acute maxillary sinusitis were referred by general practitioners for radiographs of the maxillary sinus . Those with radiographic abnormalities ( n = 214 ) were r and omly assigned treatment with amoxycillin ( 750 mg three times daily for 7 days ; n = 108 ) or placebo ( n = 106 ) . Clinical course was assessed after 1 week and 2 weeks , and reported relapses and complications were recorded during the following year . FINDINGS After 2 weeks , symptoms had improved substantially or disappeared in 83 % of patients in the study group and 77 % of patients taking placebo . Amoxycillin did not influence the clinical course of maxillary sinusitis nor the frequency of relapses during the 1-year follow-up . Radiographs had no prognostic value , nor were they an effect modifier . Side-effects were recorded in 28 % of patients given amoxycillin and in 9 % of those taking placebo ( p < 0.01 ) . The occurrence of relapses was similar in both groups ( 21 vs 17 % ) during the follow-up year . INTERPRETATION Antibiotic treatment did not improve the clinical course of acute maxillary sinusitis presenting to general practice . For these patients , an initial radiographic examination is not necessary and initial management can be limited to symptomatic treatment . Whether antibiotics are necessary in more severe cases warrants further study Very few investigations comparing the results of different therapeutic measures in acute sinusitis have been reported . The present investigation is an attempt to evaluate objective ly the clinical course in treated acute maxillary sinusitis by the aid of radiological registration of the sinus state . Difficulties were encountered in establishing a radiological gradation corresponding to the clinical state in the diseased sinus . A radiological gradation is suggested . A group treated with nasal decongestant only , may be regarded as a control group . The results of the treatment by nasal decongestant combined with irrigation or penicillin V or lincomycin respectively were similar and significantly better than in the control group . The patient 's evaluation of the treatment after 5 days did not correlate with the radiological state but did so after 10 days OBJECTIVE To compare the effectiveness of penicillin V with placebo in the treatment of adult patients with acute maxillary sinusitis in general practice . DESIGN R and omised , double blind , placebo controlled trial . SETTING 26 Danish general practice s. PATIENTS 133 adult patients with a clinical diagnosis of acute maxillary sinusitis based on maxillary pain and raised values of either C-reactive protein ( CRP ) or erythrocyte sedimentation rate ( ESR ) . MAIN OUTCOME MEASURES Pain score and illness score as well as measurement of CRP and ESR values after initiation of treatment . RESULTS Penicillin V led to a better recovery than did placebo . The difference was statistically significant 3 days after the initiation of treatment with regard to pain reduction , whereas no significant difference was found with regard to the reduction in the sense of illness . At the end of the study , significantly more patients in the penicillin group were completely free of pain compared to the placebo group . This difference was only found in patients with an initial pain score of more than three . The cure rate was 71 % in the penicillin group and 37 % in the placebo group . Significantly more patients achieved normal CRP values when treated with penicillin ( 88 % ) as opposed to placebo ( 75 % ) . CONCLUSION Penicillin V is more effective than placebo in the treatment of acute maxillary sinusitis in adults in general practice , but only in patients with pronounced pain Sixty-one patients , 39 females and 22 males , with bacterial and sterile acute maxillary sinusitis were subjected to study in order to decide whether or not an oral antibiotic is necessary in the treatment of this condition when it is administered simultaneously with irrigation and nose drops . Using a double-blind method , one group of patients were given doxicycline and one group a placebo . Changes in secretion were followed macroscopically and changes in the ostial patency , rhinomanometrically . Significant differences between the recovery time of patients belonging to the doxicycline and placebo groups were not observed , neither did the sensitivity of bacteria from the secretion to doxicycline correlate with the speed of recovery in either group . The results do not indicate that recovery time in acute maxillary sinusitis can be shortened with oral administration of doxicycline |
12,978 | 31,959,857 | Use of a rush treatment phase and targeting a higher maintenance dose were associated with a higher risk and frequency of epinephrine use , while using co-treatments in addition to POIT was associated with a lower risk of treatment discontinuation due to adverse events .
While adverse events to POIT are common , this study provides promising explorative evidence that certain modifications to existing treatment protocol s could significantly improve treatment outcomes | While peanut oral immunotherapy ( POIT ) represents a promising treatment for peanut allergies in children , safety concerns remain a common barrier to widespread adoption .
We aim ed to systematic ally assess available evidence to determine the risk and frequency of adverse events occurring during POIT , and examine study -level characteristics associated with their occurrence and severity . | BACKGROUND Peanut allergy is a major public health problem that affects 1 % of the population and has no effective therapy . OBJECTIVE To examine the safety and efficacy of oral desensitization in peanut-allergic children in combination with a brief course of anti-IgE mAb ( omalizumab [ Xolair ] ) . METHODS We performed oral peanut desensitization in peanut-allergic children at high risk for developing significant peanut-induced allergic reactions . Omalizumab was administered before and during oral peanut desensitization . RESULTS We enrolled 13 children ( median age , 10 years ) , with a median peanut-specific IgE level of 229 kU(A)/L and a median total serum IgE level of 621 kU/L , who failed an initial double-blind placebo-controlled food challenge at peanut flour doses of 100 mg or less . After pretreatment with omalizumab , all 13 subjects tolerated the initial 11 desensitization doses given on the first day , including the maximum dose of 500 mg peanut flour ( cumulative dose , 992 mg , equivalent to > 2 peanuts ) , requiring minimal or no rescue therapy . Twelve subjects then reached the maximum maintenance dose of 4000 mg peanut flour per day in a median time of 8 weeks , at which point omalizumab was discontinued . All 12 subjects continued on 4000 mg peanut flour per day and subsequently tolerated a challenge with 8000 mg peanut flour ( equivalent to about 20 peanuts ) , or 160 to 400 times the dose tolerated before desensitization . During the study , 6 of the 13 subjects experienced mild or no allergic reactions , 5 subjects had grade 2 reactions , and 2 subjects had grade 3 reactions , all of which responded rapidly to treatment . CONCLUSIONS Among children with high-risk peanut allergy , treatment with omalizumab may facilitate rapid oral desensitization and qualitatively improve the desensitization process Background : Oral immunotherapy ( OIT ) is an effective experimental food allergy treatment that is limited by treatment withdrawal and the frequent reversibility of desensitization if interrupted . Newly diagnosed preschool children may have clinical and immunological characteristics more amenable to treatment . Objective : We sought to test the safety , effectiveness , and feasibility of early OIT ( E‐OIT ) in the treatment of peanut allergy . Methods : We enrolled 40 children aged 9 to 36 months with suspected or known peanut allergy . Qualifying subjects reacted to peanut during an entry food challenge and were block‐r and omized 1:1 to receive E‐OIT at goal maintenance doses of 300 or 3000 mg/d in a double‐blinded fashion . The primary end point , sustained unresponsiveness at 4 weeks after stopping early intervention oral immunotherapy ( 4‐SU ) , was assessed by double‐blinded , placebo‐controlled food challenge either upon achieving 4 prespecified criteria , or after 3 maintenance years . Peanut‐specific immune responses were serially analyzed . Outcomes were compared with 154 matched st and ard‐care controls . Results : Of 40 consented subjects , 3 ( 7.5 % ) did not qualify . Overall , 29 of 37 ( 78 % ) in the intent‐to‐treat analysis achieved 4‐SU ( 300‐mg arm , 17 of 20 [ 85 % ] ; 3000 mg , 12 of 17 [ 71 % ] , P = .43 ) over a median of 29 months . Per‐ protocol , the overall proportion achieving 4‐SU was 29 of 32 ( 91 % ) . Peanut‐specific IgE levels significantly declined in E‐OIT‐treated children , who were 19 times more likely to successfully consume dietary peanut than matched st and ard‐care controls , in whom peanut‐specific IgE levels significantly increased ( relative risk , 19.42 ; 95 % CI , 8.7‐43.7 ; P < .001 ) . Allergic side effects during E‐OIT were common but all were mild to moderate . Conclusions : At both doses tested , E‐OIT had an acceptable safety profile and was highly successful in rapidly suppressing allergic immune responses and achieving safe dietary re introduction Background : Peanut oral immunotherapy is a promising approach to peanut allergy , but reactions are frequent , and some patients can not be desensitized . The anti‐IgE medication omalizumab ( Xolair ; Genentech , South San Francisco , Calif ) might allow more rapid peanut updosing and decrease reactions . Objective : We sought to evaluate whether omalizumab facilitated rapid peanut desensitization in highly allergic patients . Methods : Thirty‐seven subjects were r and omized to omalizumab ( n = 29 ) or placebo ( n = 8) . After 12 weeks of treatment , subjects underwent a rapid 1‐day desensitization of up to 250 mg of peanut protein , followed by weekly increases up to 2000 mg . Omalizumab was then discontinued , and subjects continued on 2000 mg of peanut protein . Subjects underwent an open challenge to 4000 mg of peanut protein 12 weeks after stopping study drug . If tolerated , subjects continued on 4000 mg of peanut protein daily . Results : The median peanut dose tolerated on the initial desensitization day was 250 mg for omalizumab‐treated subjects versus 22.5 mg for placebo‐treated subject . Subsequently , 23 ( 79 % ) of 29 subjects r and omized to omalizumab tolerated 2000 mg of peanut protein 6 weeks after stopping omalizumab versus 1 ( 12 % ) of 8 receiving placebo ( P < .01 ) . Twenty‐three subjects receiving omalizumab versus 1 subject receiving placebo passed the 4000‐mg food challenge . Overall reaction rates were not significantly lower in omalizumab‐treated versus placebo‐treated subjects ( odds ratio , 0.57 ; P = .15 ) , although omalizumab‐treated subjects were exposed to much higher peanut doses . Conclusion : Omalizumab allows subjects with peanut allergy to be rapidly desensitized over as little as 8 weeks of peanut oral immunotherapy . In the majority of subjects , this desensitization is sustained after omalizumab is discontinued . Additional studies will help clarify which patients would benefit most from this approach BACKGROUND Peanut oral immunotherapy , using a variety of approaches , has been previously shown to induce desensitization in peanut-allergic subjects , but no products have been approved for clinical use by regulatory agencies . OBJECTIVE We performed the first phase 2 multicentered study to assess the safety and efficacy of AR101 , a novel oral biologic drug product . METHODS A r and omized , double-blind , placebo-controlled trial was conducted at 8 US centers . Eligible subjects were 4 to 26 years old , sensitized to peanut , and had dose-limiting symptoms to ≤143 mg of peanut protein in a screening double-blind , placebo-controlled food challenge ( DBPCFC ) . Subjects were r and omized 1:1 to daily AR101 or placebo and gradually up-dosed from 0.5 to 300 mg/day . The primary endpoint was the proportion of subjects in each arm able to tolerate ≥443 mg ( cumulative peanut protein ) at exit DBPCFC with no or mild symptoms . RESULTS Fifty-five subjects ( 29 AR101 , 26 placebo ) were enrolled . In the intention-to-treat analysis , 23 of 29 ( 79 % ) and 18 of 29 ( 62 % ) AR101 subjects tolerated ≥443 mg and 1043 mg at exit DBPCFC , respectively , versus 5 of 26 ( 19 % ) and 0 of 26 ( 0 % ) placebo subjects ( both P < .0001 ) . Compared with placebo , AR101 significantly reduced symptom severity during exit DBPCFCs and modulated peanut-specific cellular and humoral immune responses . Gastrointestinal ( GI ) symptoms were the most common treatment-related adverse events ( AEs ) in both groups , with 6 AR101 subjects ( 21 % ) withdrawing , 4 of those due primarily to recurrent GI AEs . CONCLUSIONS In this study , AR101 demonstrated an acceptable safety profile and demonstrated clinical activity as a potential immunomodulatory treatment option in peanut-allergic children over the age of 4 , adolescents , and young adults BACKGROUND Although promising results have emerged regarding oral immunotherapy ( OIT ) and sublingual immunotherapy ( SLIT ) for the treatment of peanut allergy ( PA ) , direct comparisons of these approaches are limited . OBJECTIVE This study was conducted to compare the safety , efficacy , and mechanistic correlates of peanut OIT and SLIT . METHODS In this double-blind study children with PA were r and omized to receive active SLIT/placebo OIT or active OIT/placebo SLIT . Doses were escalated to 3.7 mg/d ( SLIT ) or 2000 mg/d ( OIT ) , and subjects were rechallenged after 6 and 12 months of maintenance . After unblinding , therapy was modified per protocol to offer an additional 6 months of therapy . Subjects who passed challenges at 12 or 18 months were taken off treatment for 4 weeks and rechallenged . RESULTS Twenty-one subjects aged 7 to 13 years were r and omized . Five discontinued therapy during the blinded phase . Of the remaining 16 , all had a greater than 10-fold increase in challenge threshold after 12 months . The increased threshold was significantly greater in the active OIT group ( 141- vs 22-fold , P = .01 ) . Significant within-group changes in skin test results and peanut-specific IgE and IgG4 levels were found , with overall greater effects with OIT . Adverse reactions were generally mild but more common with OIT ( P < .001 ) , including moderate reactions and doses requiring medication . Four subjects had sustained unresponsiveness at study completion . CONCLUSION OIT appeared far more effective than SLIT for the treatment of PA but was also associated with significantly more adverse reactions and early study withdrawal . Sustained unresponsiveness after 4 weeks of avoidance was seen in only a small minority of subjects Background : Reports on oral immunotherapy ( OIT ) for anaphylactic food allergy are lacking . We investigated the efficacy and safety of peanut OIT for anaphylactic patients . Methods : We enrolled 22 peanut anaphylactic patients who underwent OIT between 2011 and 2013 , all of whom demonstrated anaphylaxis during a baseline double-blind , placebo-controlled food challenge . After starting in-hospital OIT , participants gradually increased ingestion to 795 mg of peanut protein per day at home and then took a maintenance dose ( 795 mg ) daily . After 3 asymptomatic months , participants underwent an oral food challenge ( OFC ) of 795 mg after 2 weeks of peanut avoidance to confirm sustained unresponsiveness . The historical control group consisted of 11 patients with anaphylaxis by OFC and underwent the second OFC after 2 years . Results : All patients ( 22/22 ) achieved desensitization by 8 months after starting OIT and completed the protocol within 2 years . Two years later , 15/22 patients ( 68.1 % ) in the OIT group achieved sustained unresponsiveness , whereas only 2 ( 18.1 % ) in the control group passed the second OFC . After 2 years , the median peanut-specific IgE had significantly decreased ( from 38.5 to 12.4 kUA/L ) in the OIT group , but not in the control group . Median peanut- and Ara h 2-specific IgG4 in the OIT group had significantly increased from baseline after 1 month . The adverse reaction rate per ingestion was 43 % in hospital and 5 % at home . Three patients received adrenaline at the hospital and 2 at home . Conclusions : These data suggest that for patients with peanut anaphylaxis , OIT can increase the threshold and support achieving sustained unresponsiveness with relative safety Background Peanut allergy is severe and rarely resolves BACKGROUND Open-label oral immunotherapy ( OIT ) protocol s have been used to treat small numbers of patients with peanut allergy . Peanut OIT has not been evaluated in double-blind , placebo-controlled trials . OBJECTIVE To investigate the safety and effectiveness of OIT for peanut allergy in a double-blind , placebo-controlled study . METHODS In this multicenter study , children ages 1 to 16 years with peanut allergy received OIT with peanut flour or placebo . Initial escalation , build-up , and maintenance phases were followed by an oral food challenge ( OFC ) at approximately 1 year . Titrated skin prick tests ( SPTs ) and laboratory studies were performed at regular intervals . RESULTS Twenty-eight subjects were enrolled in the study . Three peanut OIT subjects withdrew early in the study because of allergic side effects . During the double-blind , placebo-controlled food challenge , all remaining peanut OIT subjects ( n = 16 ) ingested the maximum cumulative dose of 5000 mg ( approximately 20 peanuts ) , whereas placebo subjects ( n = 9 ) ingested a median cumulative dose of 280 mg ( range , 0 - 1900 mg ; P < .001 ) . In contrast with the placebo group , the peanut OIT group showed reductions in SPT size ( P < .001 ) , IL-5 ( P = .01 ) , and IL-13 ( P = .02 ) and increases in peanut-specific IgG(4 ) ( P < .001 ) . Peanut OIT subjects had initial increases in peanut-specific IgE ( P < .01 ) but did not show significant change from baseline by the time of OFC . The ratio of forkhead box protein 3 (FoxP3)(hi ) : FoxP3(intermediate ) CD4 + CD25 + T cells increased at the time of OFC ( P = .04 ) in peanut OIT subjects . CONCLUSION These results conclusively demonstrate that peanut OIT induces desensitization and concurrent immune modulation . The current study continues and is evaluating the hypothesis that peanut OIT causes long-term immune tolerance BACKGROUND Coadministration of a bacterial adjuvant with oral immunotherapy ( OIT ) has been suggested as a potential treatment for food allergy . OBJECTIVE To evaluate a combined therapy comprising a probiotic together with peanut OIT . METHODS We performed a double-blind , placebo-controlled r and omized trial of the probiotic Lactobacillus rhamnosus CGMCC 1.3724 and peanut OIT ( probiotic and peanut oral immunotherapy [ PPOIT ] ) in children ( 1 - 10 years ) with peanut allergy . The primary outcome was induction of sustained unresponsiveness 2 to 5 weeks after discontinuation of treatment ( referred to as possible sustained unresponsiveness ) . Secondary outcomes were desensitization , peanut skin prick test , and specific IgE and specific IgG4 measurements . RESULTS Sixty-two children were r and omized and stratified by age ( ≤5 and > 5 years ) and peanut skin test wheal size ( ≤10 and > 10 mm ) ; 56 reached the trial 's end . Baseline demographics were similar across groups . Possible sustained unresponsiveness was achieved in 82.1 % receiving PPOIT and 3.6 % receiving placebo ( P < .001 ) . Nine children need to be treated for 7 to achieve sustained unresponsiveness ( number needed to treat , 1.27 ; 95 % CI , 1.06 - 1.59 ) . Of the subjects , 89.7 % receiving PPOIT and 7.1 % receiving placebo were desensitized ( P < .001 ) . PPOIT was associated with reduced peanut skin prick test responses and peanut-specific IgE levels and increased peanut-specific IgG4 levels ( all P < .001 ) . PPOIT-treated participants reported a greater number of adverse events , mostly with maintenance home dosing . CONCLUSION This is the first r and omized placebo-controlled trial evaluating the novel coadministration of a probiotic and peanut OIT and assessing sustained unresponsiveness in children with peanut allergy . PPOIT was effective in inducing possible sustained unresponsiveness and immune changes that suggest modulation of the peanut-specific immune response . Further work is required to confirm sustained unresponsiveness after a longer period of secondary peanut elimination and to clarify the relative contributions of probiotics versus OIT Summary Background Small studies suggest peanut oral immunotherapy ( OIT ) might be effective in the treatment of peanut allergy . We aim ed to establish the efficacy of OIT for the desensitisation of children with allergy to peanuts . Methods We did a r and omised controlled crossover trial to compare the efficacy of active OIT ( using characterised peanut flour ; protein doses of 2–800 mg/day ) with control ( peanut avoidance , the present st and ard of care ) at the NIHR/Wellcome Trust Cambridge Clinical Research Facility ( Cambridge , UK ) . R and omisation ( 1:1 ) was by use of an audited online system ; group allocation was not masked . Eligible participants were aged 7–16 years with an immediate hypersensitivity reaction after peanut ingestion , positive skin prick test to peanuts , and positive by double-blind placebo-controlled food challenge ( DBPCFC ) . We excluded participants if they had a major chronic illness , if the care provider or a present household member had suspected or diagnosed allergy to peanuts , or if there was an unwillingness or inability to comply with study procedures . Our primary outcome was desensitisation , defined as negative peanut challenge ( 1400 mg protein in DBPCFC ) at 6 months ( first phase ) . Control participants underwent OIT during the second phase , with subsequent DBPCFC . Immunological parameters and disease-specific quality -of-life scores were measured . Analysis was by intention to treat . Fisher 's exact test was used to compare the proportion of those with desensitisation to peanut after 6 months between the active and control group at the end of the first phase . This trial is registered with Current Controlled Trials , number IS RCT N62416244 . Findings The primary outcome , desensitisation , was recorded for 62 % ( 24 of 39 participants ; 95 % CI 45–78 ) in the active group and none of the control group after the first phase ( 0 of 46 ; 95 % CI 0–9 ; p<0·001 ) . 84 % ( 95 % CI 70–93 ) of the active group tolerated daily ingestion of 800 mg protein ( equivalent to roughly five peanuts ) . Median increase in peanut threshold after OIT was 1345 mg ( range 45–1400 ; p<0·001 ) or 25·5 times ( range 1·82–280 ; p<0·001 ) . After the second phase , 54 % ( 95 % CI 35–72 ) tolerated 1400 mg challenge ( equivalent to roughly ten peanuts ) and 91 % ( 79–98 ) tolerated daily ingestion of 800 mg protein . Quality -of-life scores improved ( decreased ) after OIT ( median change −1·61 ; p<0·001 ) . Side-effects were mild in most participants . Gastrointestinal symptoms were , collectively , most common ( 31 participants with nausea , 31 with vomiting , and one with diarrhoea ) , then oral pruritus after 6·3 % of doses ( 76 participants ) and wheeze after 0·41 % of doses ( 21 participants ) . Intramuscular adrenaline was used after 0·01 % of doses ( one participant ) . Interpretation OIT successfully induced desensitisation in most children within the study population with peanut allergy of any severity , with a clinical ly meaningful increase in peanut threshold . Quality of life improved after intervention and there was a good safety profile . Immunological changes corresponded with clinical desensitisation . Further studies in wider population s are recommended ; peanut OIT should not be done in non-specialist setting s , but it is effective and well tolerated in the studied age group . Funding MRC-NIHR partnership Background : Peanut allergy is the leading cause of food-related anaphylaxis , and accidental exposures are common . Oral immunotherapy ( OIT ) has been posited as a potential treatment . Methods : Patients aged 3–65 years with peanut-specific IgE ≥7 kU/l and /or a positive skin prick test with a history of an allergic reaction to peanut were recruited to undergo an OIT protocol . All adverse reactions were recorded by research staff or patients in real time . Results : Twenty-four patients received 6,662 doses . Symptoms were mostly mild ( 84 % ) , and only 3 severe gastrointestinal reactions required the administration of epinephrine . Abdominal pain was the most common reaction , followed by oropharyngeal and lip pruritus . Respiratory symptoms were rare . Conclusions : In this trial of OIT in adults and children , most reactions were mild BACKGROUND Oral immunotherapy ( OIT ) offers a promising therapeutic option for peanut allergy . Given that during OIT an allergic patient ingests an allergen that could potentially cause a serious reaction , the safety of OIT is of particular concern . OBJECTIVE The purpose of this study was to examine safety during the initial escalation day , buildup phase , and home dosing phase in subjects enrolled in a peanut OIT study . METHODS Skin , upper respiratory tract , chest , and abdominal symptoms were recorded with initial escalation day and buildup phase dosings . Subjects also maintained daily diaries detailing symptoms after each home dosing . A statistical analysis of these data was performed . RESULTS Twenty of 28 patients completed all phases of the study . During the initial escalation day , upper respiratory tract ( 79 % ) and abdominal ( 68 % ) symptoms were the most likely symptoms experienced . The risk of mild wheezing during the initial escalation day was 18 % . The probability of having any symptoms after a buildup phase dose was 46 % , with a risk of 29 % for upper respiratory tract symptoms and 24 % for skin symptoms . The risk of reaction with any home dose was 3.5 % . Upper respiratory tract ( 1.2 % ) and skin ( 1.1 % ) symptoms were the most likely after home doses . Treatment was given with 0.7 % of home doses . Two subjects received epinephrine after 1 home dose each . CONCLUSIONS Subjects were more likely to have significant allergic symptoms during the initial escalation day when they were in a closely monitored setting than during other phases of the study . Allergic reactions with home doses were rare Between 1973 and 1985 , 114 children , aged 2 to 14 years , underwent double-blind , placebo-controlled , food challenge ( DBPCFC ) to peanut . Thirty-two of 46 children with symptoms produced by DBPCFC to peanut were included in this longitudinal evaluation . Contact was made with the 32 subjects 2 to 14 years after their positive DBPCFC to peanut . All 32 subjects had exhibited a positive puncture skin test to peanut at the time of the original evaluation . Sixteen subjects had experienced symptoms caused by accidental peanut ingestion in the year before contact . Eight subjects had reacted to accidental ingestion in more than 1 year but less than 5 years before contact . Eight subjects had completely avoided peanut since the original evaluation and positive DBPCFC . No subjects could be demonstrated to have " outgrown " their peanut reactivity . All subjects tested continued to have skin reactivity to a puncture skin test with peanut extract . It appears uncommon for peanut-sensitive patients to lose their clinical reactivity , even after many years have elapsed . In addition , data were collected concerning reactions to other legumes and other ( nonlegume ) nuts . Only two patients with DBPCFC to peanut reacted on DBPCFC to soy or pea ( one each ) . None of the subjects with a positive DBPCFC to peanut reacted to nonlegume nuts BACKGROUND Oral immunotherapy ( OIT ) has been thought to induce clinical desensitization to allergenic foods , but trials coupling the clinical response and immunologic effects of peanut OIT have not been reported . OBJECTIVE The study objective was to investigate the clinical efficacy and immunologic changes associated with OIT . METHODS Children with peanut allergy underwent an OIT protocol including initial day escalation , buildup , and maintenance phases , and then oral food challenge . Clinical response and immunologic changes were evaluated . RESULTS Of 29 subjects who completed the protocol , 27 ingested 3.9 g peanut protein during food challenge . Most symptoms noted during OIT resolved spontaneously or with antihistamines . By 6 months , titrated skin prick tests and activation of basophils significantly declined . Peanut-specific IgE decreased by 12 to 18 months , whereas IgG(4 ) increased significantly . Serum factors inhibited IgE-peanut complex formation in an IgE-facilitated allergen binding assay . Secretion of IL-10 , IL-5 , IFN-gamma , and TNF-alpha from P BMC s increased over a period of 6 to 12 months . Peanut-specific forkhead box protein 3 T cells increased until 12 months and decreased thereafter . In addition , T-cell microarrays showed downregulation of genes in apoptotic pathways . CONCLUSION Oral immunotherapy induces clinical desensitization to peanut , with significant longer-term humoral and cellular changes . Microarray data suggest a novel role for apoptosis in OIT BACKGROUND The aim was to study the clinical efficacy and safety of rush oral immunotherapy ( OIT ) for severe peanut-allergic children and to measure the antibody responses . METHODS Eighteen Japanese children were enrolled after a positive double-blind , placebo-controlled food challenge ( DBPCFC ) . The patients ingested peanuts up to 3 - 5 times a day every 30 min , increasing the dose by 20 % every time . The goal dose was 3.5 - 7 g. IgE , IgG , and IgG4 antibody levels to peanut , and peanut allergen components were measured during up to 3 yr of maintenance treatment . RESULTS Two children dropped out due to side effects . Sixteen patients ( 14 boys and two girls , median : 9 yr range : 5 - 14 yr ) achieved the goal dose after a median of 11 days ( range : 4 - 19 days ) . Their median threshold dose at DBPCFC was 0.20 g ( range : 0.015 - 1.0 g ) . All were sensitized to Ara h 2 . Fourteen of them had a history of previous anaphylaxis . In total , 173 adverse events were observed during the treatment ( 27 % of the total ingestions ) of which 74 needed medications . The median IgE , IgG , and IgG4 antibody levels to peanut increased during rush OIT . The IgG4 levels were high during the whole maintenance phase . IgE and IgG4 antibodies to Ara h 2 dominated the serological response during the treatment . CONCLUSIONS The present rush OIT protocol for children with severe peanut allergy was effective and relatively safe . A sustained Ara h 2-specific IgG4 antibody response characterized the treatment BACKGROUND Only 2 small placebo-controlled trials on peanut oral immunotherapy ( OIT ) have been published . OBJECTIVE We examined the efficacy , safety , immunologic parameters , quality of life ( QOL ) , and burden of treatment ( BOT ) of low-dose peanut OIT in a multicenter , double-blind , r and omized placebo-controlled trial . METHODS A total of 62 children aged 3 to 17 years with IgE-mediated , challenge-proven peanut allergy were r and omized ( 1:1 ) to receive peanut OIT with a maintenance dose of 125 to 250 mg peanut protein or placebo . The primary outcome was the proportion of children tolerating 300 mg or more peanut protein at oral food challenge ( OFC ) after 16 months of OIT . We measured the occurrence of adverse events ( AEs ) , immunologic changes , and QOL before and after OIT and BOT during OIT . RESULTS Twenty-three of 31 ( 74.2 % ) children of the active group tolerated at least 300 mg peanut protein at final OFC compared with 5 of 31 ( 16.1 % ) in the placebo group ( P < .001 ) . Thirteen of 31 ( 41.9 % ) children of the active versus 1 of 31 ( 3.2 % ) of the placebo group tolerated the highest dose of 4.5 g peanut protein at final OFC ( P < .001 ) . There was no significant difference between the groups in the occurrence of AE-related dropouts or in the number , severity , and treatment of objective AEs . In the peanut-OIT group , we noted a significant reduction in peanut-specific IL-4 , IL-5 , IL-10 , and IL-2 production by P BMC s compared with the placebo group , as well as a significant increase in peanut-specific IgG4 levels and a significant improvement in QOL ; 86 % of children evaluated the BOT positively . DISCUSSION Low-dose OIT is a promising , effective , and safe treatment option for peanut-allergic children , leading to improvement in QOL , a low BOT , and immunologic changes showing tolerance development Background Peanut allergy , for which there are no approved treatment options , affects patients who are at risk for unpredictable and occasionally life‐threatening allergic reactions . Methods In a phase 3 trial , we screened participants 4 to 55 years of age with peanut allergy for allergic dose‐limiting symptoms at a challenge dose of 100 mg or less of peanut protein ( approximately one third of a peanut kernel ) in a double‐blind , placebo‐controlled food challenge . Participants with an allergic response were r and omly assigned , in a 3:1 ratio , to receive AR101 ( a peanut‐derived investigational biologic oral immunotherapy drug ) or placebo in an escalating‐dose program . Participants who completed the regimen ( i.e. , received 300 mg per day of the maintenance regimen for approximately 24 weeks ) underwent a double‐blind , placebo‐controlled food challenge at trial exit . The primary efficacy end point was the proportion of participants 4 to 17 years of age who could ingest a challenge dose of 600 mg or more , without dose‐limiting symptoms . Results Of the 551 participants who received AR101 or placebo , 496 were 4 to 17 years of age ; of these , 250 of 372 participants ( 67.2 % ) who received active treatment , as compared with 5 of 124 participants ( 4.0 % ) who received placebo , were able to ingest a dose of 600 mg or more of peanut protein , without dose‐limiting symptoms , at the exit food challenge ( difference , 63.2 percentage points ; 95 % confidence interval , 53.0 to 73.3 ; P<0.001 ) . During the exit food challenge , the maximum severity of symptoms was moderate in 25 % of the participants in the active‐drug group and 59 % of those in the placebo group and severe in 5 % and 11 % , respectively . Adverse events during the intervention period affected more than 95 % of the participants 4 to 17 years of age . A total of 34.7 % of the participants in the active‐drug group had mild events , as compared with 50.0 % of those in the placebo group ; 59.7 % and 44.4 % of the participants , respectively , had events that were grade d as moderate , and 4.3 % and 0.8 % , respectively , had events that were grade d as severe . Efficacy was not shown in the participants 18 years of age or older . Conclusions In this phase 3 trial of oral immunotherapy in children and adolescents who were highly allergic to peanut , treatment with AR101 result ed in higher doses of peanut protein that could be ingested without dose‐limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo . ( Funded by Aim mune Therapeutics ; PALISADE Clinical Trials.gov number , NCT02635776 . BACKGROUND Oral immunotherapy ( OIT ) can lead to desensitization to food allergens , but patients can experience treatment-related symptoms of allergic reactions that cause anxiety and treatment dropout . Interventions to improve OIT for patients are needed . OBJECTIVE To determine whether fostering the mindset that non-life-threatening symptoms during OIT can signal desensitization improves treatment experience and outcomes . METHODS In a r and omized , blinded , controlled phase II study , 50 children/adolescents ( 28 % girls , aged 7 - 17 years , M = 10.82 , st and ard deviation = 3.01 ) completed 6-month OIT for peanut allergies . Patients and their parent(s ) had monthly clinic visits at the Sean N. Parker Center for Allergy and Asthma Research between January 5 , 2017 , and August 3 , 2017 . All families received identical symptom management training . In a 1:1 approach , 24 patients and their families were informed that non-life-threatening symptoms during OIT were unfortunate side effects of treatment , and 26 patients and their families were informed that non-life-threatening symptoms could signal desensitization . Families participated in activities to reinforce these symptom mindsets . RESULTS Compared with families informed that symptoms are side effects , families informed that symptoms can signal desensitization were less anxious ( B = -0.46 , 95 % confidence interval [ CI ] : -0.76 to -0.16 ; P = .003 ) , less likely to contact staff about symptoms ( 5/24 [ 9.4 % ] vs 27/154 [ 17.5 % ] instances ; P = .036 ) , experienced fewer non-life-threatening symptoms as doses increased ( BInteraction = -0.54 , 95 % CI : -0.83 to -0.27 ; P < .001 ) , less likely to skip/reduce doses ( 1/26 [ 4 % ] vs 5/24 [ 21 % ] patients ; P = .065 ) , and showed a greater increase in patient peanut-specific blood IgG4 levels ( BInteraction = 0.76 , 95 % CI : 0.36 to 1.17 ; P < .001 ) . CONCLUSIONS Fostering the mindset that symptoms can signal desensitization improves OIT experience and outcomes . Changing how providers inform patients about non-life-threatening symptoms is a promising avenue for improving treatment |
12,979 | 32,046,735 | Pre-emptive avoidance of RGBs during the initial testing of an intervention may diminish the voltage drop between pilot and larger efficacy/effectiveness trials and enhance the odds of successful translation | BACKGROUND Preliminary evaluations of behavioral interventions , referred to as pilot studies , pre date the conduct of many large-scale efficacy/effectiveness trial .
The ability of a pilot study to inform an efficacy/effectiveness trial relies on careful considerations in the design , delivery , and interpretation of the pilot results to avoid exaggerated early discoveries that may lead to subsequent failed efficacy/effectiveness trials . "
Risk of generalizability biases ( RGB ) " in pilot studies may reduce the probability of replicating results in a larger efficacy/effectiveness trial .
We aim ed to generate an operational list of potential RGBs and to evaluate their impact in pairs of published pilot studies and larger , more well-powered trial on the topic of childhood obesity . | Pilot studies for phase III trials - which are comparative r and omized trials design ed to provide preliminary evidence on the clinical efficacy of a drug or intervention - are routinely performed in many clinical areas . Also commonly know as " feasibility " or " vanguard " studies , they are design ed to assess the safety of treatment or interventions ; to assess recruitment potential ; to assess the feasibility of international collaboration or coordination for multicentre trials ; to increase clinical experience with the study medication or intervention for the phase III trials . They are the best way to assess feasibility of a large , expensive full-scale study , and in fact are an almost essential pre-requisite . Conducting a pilot prior to the main study can enhance the likelihood of success of the main study and potentially help to avoid doomed main studies . The objective of this paper is to provide a detailed examination of the key aspects of pilot studies for phase III trials including : 1 ) the general reasons for conducting a pilot study ; 2 ) the relationships between pilot studies , proof-of-concept studies , and adaptive design s ; 3 ) the challenges of and misconceptions about pilot studies ; 4 ) the criteria for evaluating the success of a pilot study ; 5 ) frequently asked questions about pilot studies ; 7 ) some ethical aspects related to pilot studies ; and 8) some suggestions on how to report the results of pilot investigations using the CONSORT format OBJECTIVE To test the feasibility , acceptability , and potential efficacy of after-school dance classes and a family-based intervention to reduce television viewing , thereby reducing weight gain , among African-American girls . DESIGN Twelve-week , 2-arm parallel group , r and omized controlled trial . SETTING Low-income neighborhoods . PARTICIPANTS Sixty-one 8 - 10-year-old African-American girls and their parents/guardians . INTERVENTIONS The treatment intervention consisted of after-school dance classes at 3 community centers , and a 5-lesson intervention , delivered in participants ' homes , and design ed to reduce television , videotape , and video game use . The active control intervention consisted of disseminating newsletters and delivering health education lectures . MAIN OUTCOME MEASURES Implementation and process measures , body mass index , waist circumference , physical activity measured by accelerometry , self-reported media use , and meals eaten with TV . RESULTS Recruitment and retention goals were exceeded . High rates of participation were achieved for assessment s and intervention activities , except where transportation was lacking . All interventions received high satisfaction ratings . At follow up , girls in the treatment group , as compared to the control group , exhibited trends toward lower body mass index ( adjusted difference = -.32 kg/m2 , 95 % confidence interval [ CI ] -.77 , .12 ; Cohen 's d = .38 st and ard deviation units ) and waist circumference ( adjusted difference = -.63 cm , 95 % CI -1.92 , .67 ; d = .25 ) ; increased after-school physical activity ( adjusted difference = 55.1 counts/minute , 95 % CI -115.6 , 225.8 ; d = .21 ) ; and reduced television , videotape , and video game use ( adjusted difference = -4.96 hours/week , 95 % CI -11.41 , 1.49 ; d = .40 ) . The treatment group reported significantly reduced household television viewing ( d = .73 , P = .007 ) and fewer dinners eaten while watching TV ( adjusted difference = -1.60 meals/week , 95 % CI -2.99 , -.21 ; d = .59 ; P = .03 ) . Treatment group girls also reported less concern about weight ( d = .60 ; P = .03 ) , and a trend toward improved school grade s ( d = .51 ; P = .07 ) . CONCLUSIONS This study confirmed the feasibility , acceptability , and potential efficacy of using dance classes and a family-based intervention to reduce television viewing , thereby reducing weight gain , in African-American girls To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results Developing an evidence base for making public health decisions will require using data from evaluation studies with r and omized and nonr and omized design s. Assessing individual studies and using studies in quantitative research syntheses require transparent reporting of the study , with sufficient detail and clarity to readily see differences and similarities among studies in the same area . The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement provides guidelines for transparent reporting of r and omized clinical trials . We present the initial version of the Transparent Reporting of Evaluations with Nonr and omized Design s ( TREND ) statement . These guidelines emphasize the reporting of theories used and descriptions of intervention and comparison conditions , research design , and methods of adjusting for possible biases in evaluation studies that use nonr and omized design OBJECTIVE The objective of the current study was to examine the effectiveness of a multidisciplinary weekly family-based behavioral group delivered via telemedicine to rural areas , compared with a st and ard physician visit intervention . METHODS A r and omized controlled trial was conducted with 58 rural children and their families comparing a family-based behavioral intervention delivered via telemedicine to a structured physician visit condition . Outcome measures included child body mass index z-score ( BMI z ) , 24-hr dietary recalls , accelerometer data , Child Behavior Checklist , Behavioral Pediatrics Feeding Assessment Scale , and feasibility and fidelity . RESULTS Child BMI z outcomes were not statistically different between the 2 groups ( F = 0.023 , p = .881 ) . Improvements in BMI z , nutrition , and physical activity were seen for both groups . CONCLUSIONS Both telemedicine and structured physician visit may be feasible and acceptable methods of delivering pediatric obesity treatment to rural children Summary Background Although childhood overweight and obesity prevalence has increased substantially worldwide in the past three decades , scarce evidence exists for effective preventive strategies . We aim ed to establish whether a school-based intervention for children aged 9–10 years would prevent excessive weight gain after 24 months . Methods This pragmatic cluster r and omised controlled trial of the Healthy Lifestyles Programme ( HeLP ) , a school-based obesity prevention intervention , was done in 32 schools in southwest Engl and . All state-run primary and junior schools in Devon and Plymouth ( UK ) with enough pupils for at least one year-5 class were eligible . Schools were assigned ( 1:1 ) using a computer-generated sequence to either intervention or control , stratified by the number of year-5 classes ( one vs more than one ) and the proportion of children eligible for free school meals ( < 19 % [ the national average ] vs ≥19 % ) . HeLP was delivered to year-5 children ( ages 9–10 years ) over 1 year , and included dynamic and interactive activities such as physical activity workshops , education sessions delivered by teachers with short homework tasks , drama sessions , and setting goals to modify behaviour ( with parental support and one-to-one discussion s with HeLP coordinators ) . The primary outcome was change in body-mass index ( BMI ) st and ard deviation score ( SDS ) between baseline and 24 months , analysed in children with BMI data available for both timepoints . This study is registered with the International St and ard R and omised Controlled Trial register , number IS RCT N15811706 , and the trial status is complete . Findings Between March 21 , 2012 , and Sept 30 , 2013 , 32 eligible schools with 1324 children were recruited , of which 16 schools ( 676 children ) were r and omly assigned to the HeLP intervention and 16 schools ( 648 children ) to control . All schools that began the trial completed the intervention , and 1244 children ( 628 in intervention group and 616 in control group ) had BMI data at both baseline and 24 months for the primary outcome analysis . Mean BMI SDS was 0·32 ( SD 1·16 ) at baseline and 0·35 ( 1·25 ) at 24 months in the intervention group , and 0·18 ( 1·14 ) at baseline and 0·22 ( 1·22 ) at 24 months in the control group . With adjustment for school-level clustering , baseline BMI scores , sex , cohort , and number of year-5 classes and socioeconomic status of each school , the mean difference in BMI SDS score ( intervention – control ) at 24 months was −0·02 ( 95 % CI −0·09 to 0·05 ) , p=0·57 . One parent reported an adverse event related to their child 's eating and activity behaviours , but agreed for the child to continue trial participation after discussion with the chief investigator . Interpretation Despite a theoretically informed and extensively piloted intervention that achieved high levels of engagement , follow-up , and fidelity of delivery , we found no effect of the intervention on preventing overweight or obesity . Although schools are an ideal setting in which to deliver population -based interventions , school-based interventions might not be sufficiently intense to affect both the school and the family environment , and hence the weight status of children . Future research should focus on more upstream determinants of obesity and use whole-systems approaches . Funding UK National Institute for Health Research , Public Health Research Programme Background The bias toward immediate gratification is associated with maladaptive eating behaviors and has been cross-sectionally and prospect ively related to obesity . Engaging in episodic future thinking , which involves mental self-projection to pre-experience future events , reduces this bias and energy intake in overweight/obese adults and children . To examine how episodic future thinking can be incorporated into clinical interventions , a Web-based system was created to provide training for adults and children in their everyday lives . Objective Our study examined the technical feasibility , usability , and acceptability of a Web-based system that is accessible by mobile devices and adapts episodic future thinking for delivery in family-based obesity interventions . Methods We recruited 20 parent-child dyads ( N=40 ) from the surrounding community and r and omized to episodic future thinking versus a nutritional information thinking control to test the feasibility of a 4-week Web-based intervention . Parents were 44.1 ( SD 7.8 ) years of age with BMI of 34.2 ( SD 6.8 ) kg/m2 . Children were 11.0 ( SD 1.3 ) years of age with BMI percentile of 96.0 ( SD 1.8 ) . Families met weekly with a case manager for 4 weeks and used the system daily . Adherence was collected through the Web-based system , and perceived acceptance of the Web-based system was assessed postintervention . Measurements of body composition and dietary intake were collected at baseline and after the 4 weeks of intervention . Results All 20 families completed the intervention and attended all sessions . Results showed parents and children had high adherence to the Web-based system and perceived it to be easy to use , useful , and helpful . No differences between conditions were found in adherence for parents ( P=.65 ) or children ( P=.27 ) . In addition , results suggest that basic nutrition information along with episodic future thinking delivered through our Web-based system may reduce energy intake and weight . Conclusions We showed that our Web-based system is an accepted technology and a feasible utility . Furthermore , results provide initial evidence that our system can be incorporated into family-based treatments targeting behaviors related to weight control . These results show promising utility in using our Web-based system in interventions This study explored a community-based after-school program ’s effect on obesity in minority children . Study participants included 178 third through fifth grade rs ( 47 % Latino , 25 % Asian , and 18 % African-American ) enrolled in America SCORES Bay Area . Outcomes were attendance , change in fitness ( 20-meter shuttle test ) , and body mass index ( BMI ) z-score over eight months . At baseline , 52 percent of children were overweight or obese . Children attended SCORES > 4 days/week and fitness significantly improved ( p < 0.01 ) . BMI z-score decreased by 0.04 ( p = 0.10 ) overall , and by 0.05 ( p = 0.08 ) among obese children , but increased among African-American children . These results suggest that SCORES increases fitness and may improve BMI in some minority children . Effect modification by race may relate to differential growth patterns or engagement in SCORES . These findings suggest community-based programs could effectively address obesity . A r and omized trial of the SCORES program is warranted to rigorously examine this type of after-school program ’s impact on child health To assess the feasibility of conducting empirically supported family-based paediatric obesity group treatment via TeleMedicine . Seventeen families were r and omly assigned to one of two conditions ( physician visit , TeleMedicine ) . Measures included feasibility , satisfaction and intervention outcome measures such as BMI percentile , and nutrition and activity behaviours . Measures were completed at baseline , post-treatment and at 1-year follow-up . Analyses indicate that both feasibility and satisfaction data regarding the TeleMedicine intervention were positive . Intervention outcome indicates no change in BMI percentile or nutrition and activity behaviours for either treatment group . A behavioural family-based weight loss intervention delivered via TeleMedicine was well received by both parents and providers . Due to the small sample size , null findings regarding intervention outcome should be interpreted with caution . Future research should focus on methods to increase the impact of this intervention on key outcome variables Background To address the public health crisis of overweight and obese preschool-age children , the Nutrition And Physical Activity Self Assessment for Child Care ( NAP SACC ) intervention was delivered by nurse child care health consultants with the objective of improving child care provider and parent nutrition and physical activity knowledge , center-level nutrition and physical activity policies and practice s , and children ’s body mass index ( BMI ) . Methods A seven-month r and omized control trial was conducted in 17 licensed child care centers serving predominantly low income families in California , Connecticut , and North Carolina , including 137 child care providers and 552 families with racially and ethnically diverse children three to five years old . The NAP SACC intervention included educational workshops for child care providers and parents on nutrition and physical activity and consultation visits provided by trained nurse child care health consultants . Demographic characteristics and pre - and post-workshop knowledge surveys were completed by providers and parents . Blinded research assistants review ed each center ’s written health and safety policies , observed nutrition and physical activity practice s , and measured r and omly selected children ’s nutritional intake , physical activity , and height and weight pre- and post-intervention . Results Hierarchical linear models and multiple regression models assessed individual- and center-level changes in knowledge , policies , practice s and age- and sex-specific st and ardized body mass index ( z BMI ) , controlling for state , parent education , and poverty level . Results showed significant increases in providers ’ and parents ’ knowledge of nutrition and physical activity , center-level improvements in policies , and child-level changes in children ’s z BMI based on 209 children in the intervention and control centers at both pre- and post-intervention time points . Conclusions The NAP SACC intervention , as delivered by trained child health professionals such as child care health consultants , increases provider knowledge , improves center policies , and lowers BMI for children in child care centers . More health professionals specifically trained in a nutrition and physical activity intervention in child care are needed to help reverse the obesity epidemic . Trial registration National Clinical Trials Number BACKGROUND Effective programmes to help children manage their weight are required . ' Families for Health ' focuses on a parenting approach , design ed to help parents develop their parenting skills to support lifestyle change within the family . Families for Health version 1 showed sustained reductions in mean body mass index ( BMI ) z-score after 2 years in a pilot project . OBJECTIVE The aim was to evaluate its effectiveness and cost-effectiveness in a r and omised controlled trial ( RCT ) . DESIGN The trial was a multicentre , investigator-blind RCT , with a parallel economic and process evaluation , with follow-up at 3 and 12 months . R and omisation was by family unit , using a 1 : 1 allocation by telephone registration , stratified by three sites , with a target of 120 families . SETTING Three sites in the West Midl and s , Engl and , UK . PARTICIPANTS Children aged 6 - 11 years who were overweight ( ≥ 91st centile BMI ) or obese ( ≥ 98th centile BMI ) , and their parents/carers . Recruitment was via referral or self-referral . INTERVENTIONS Families for Health version 2 is a 10-week , family-based community programme with parallel groups for parents and children , addressing parenting , lifestyle , social and emotional development . Usual care was the treatment for childhood obesity provided within each locality . MAIN OUTCOME MEASURES Joint primary outcome measures were change in children 's BMI z-score and incremental cost per quality -adjusted life-year ( QALY ) gained at 12 months ' follow-up ( QALYs were calculated using the European Quality of Life-5 Dimensions Youth version ) . Secondary outcome measures included changes in children 's waist circumference , percentage body fat , physical activity , fruit/vegetable consumption and quality of life . Parents ' BMI and mental well-being , family eating/activity , parent-child relationships and parenting style were also assessed . The process evaluation documented recruitment , reach , dose delivered , dose received and fidelity , using mixed methods . RESULTS The study recruited 115 families ( 128 children ; 63 boys and 65 girls ) , with 56 families r and omised to the Families for Health arm and 59 to the ' usual-care ' control arm . There was 80 % retention of families at 3 months ( Families for Health , 46 families ; usual care , 46 families ) and 72 % retention at 12 months ( Families for Health , 44 families ; usual care , 39 families ) . The change in BMI z-score at 12 months was not significantly different in the Families for Health arm and the usual-care arm [ 0.114 , 95 % confidence interval ( CI ) -0.001 to 0.229 ; p = 0.053 ] . However , within-group analysis showed that the BMI z-score was significantly reduced in the usual-care arm ( -0.118 , 95 % CI -0.203 to -0.034 ; p = 0.007 ) , but not in the Families for Health arm ( -0.005 , 95 % CI -0.085 to 0.078 ; p = 0.907 ) . There was only one significant difference between groups for secondary outcomes . The economic evaluation , taking a NHS and Personal Social Services perspective , showed that mean costs 12 months post r and omisation were significantly higher for Families for Health than for usual care ( £ 998 vs. £ 548 ; p < 0.001 ) . The mean incremental cost-effectiveness of Families for Health was estimated at £ 552,175 per QALY gained . The probability that the Families for Health programme is cost-effective did not exceed 40 % across a range of thresholds . The process evaluation demonstrated that the programme was implemented , as planned , to the intended population and any adjustments did not deviate widely from the h and book . Many families waited more than 3 months to receive the intervention . Facilitators ' , parents ' and children 's experiences of Families for Health were largely positive and there were no adverse events . Further analysis could explore why some children show a clinical ly significant benefit while others have a worse outcome . CONCLUSIONS Families for Health was neither effective nor cost-effective for the management of obesity in children aged 6 - 11 years , in comparison with usual care . Further exploration of the wide range of responses in BMI z-score in children following the Families for Health and usual-care interventions is warranted , focusing on children who had a clinical ly significant benefit and those who showed a worse outcome with treatment . Further research could focus on the role of parents in the prevention of obesity , rather than treatment . TRIAL REGISTRATION Current Controlled Trials IS RCT N45032201 . FUNDING This project was funded by the National Institute for Health Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 21 , No. 1 . See the NIHR Journals Library website for further project information The goal of evidence -based medicine is ultimately to improve patient outcomes and quality of care . Systematic review s of the available published evidence are required to identify interventions that lead to improvements in behavior , health , and well-being . Authoritative literature review s depend on the quality of published research and research reports . The Consoli date d St and ards for Reporting Trials ( CONSORT ) Statement ( www.consort-statement.org ) was developed to improve the design and reporting of interventions involving r and omized clinical trials ( RCTs ) in medical journals . We describe the 22 CONSORT guidelines and explain their application to behavioral medicine research and to evidence -based practice . Additional behavioral medicine-specific guidelines ( e.g. , treatment adherence ) are also presented . Use of these guidelines by clinicians , educators , policymakers , and research ers who design , report , and evaluate or review RCTs will strengthen the research itself and accelerate efforts to apply behavioral medicine research to improve the processes and outcomes of behavioral medicine practice Background : Previous studies have shown that choice and self-initiated behavior change are important for increasing intrinsic motivation and physical activity ( PA ) , however , little of this research has focused on underserved adolescents . Purpose : This study examined the effects of a 4-week student-centered intervention on increasing PA in underserved adolescents . Methods : Twenty-eight students in the intervention school were matched ( on race , percentage on free or reduced-price lunch program , gender , and age ) with 20 students from another school who served as the comparison group ( 30 girls , 18 boys ; ages 10–12 years ; 83 % African American ; 83 % on free or reduced-price lunch ) . The student-centered intervention was consistent with self-determination ( motivation ) theory and social cognitive theory in that it emphasized increasing intrinsic motivation and behavioral skills for PA . Intervention adolescents took ownership in selecting a variety of PA activities in which to participate , and they generated coping strategies for making effective PA behavior changes . Results : Intervention participants showed greater increases in accelerometer estimates of time spent in moderate PA , moderate-to-vigorous PA , and vigorous PA from baseline to Week 4 of the intervention than the comparison group . Intervention participants also showed greater increases in PA motivation and positive self-concept for PA than comparison adolescents . Conclusions : This study provides preliminary evidence that increasing adolescent involvement and choice of activities may be important in developing future PA interventions for underserved adolescents To evaluate the intervention effects of r and omized controlled trials ( RCT ) involved in theoretical efficacy and actual clinical outcome ( effectiveness ) . Pragmatic-Explanatory Continuum Indicator Summary ( PRECIS ) is a tool to help research ers make decisions in study design which is consistent with the intended purpose of their trial which can be used in the design of RCT to balance the internal validity and external validity . The role of PRECIS has been gradually recognized in the practice of design ing clinical trials . To ensure that the design choices are concordant with the intention and the facilitation of use set by patients , clinicians and policy makers , a new PRECIS-2 tool has been developed by mangy international team experts under modification and upgrading the existing PRECIS . The PRECIS-2 tool mainly focuses on trial design choices which determining the applicability of a trial . PRECIS-2 has nine domains , with each of them intends to help the research ers consider the consequences of that design decision in terms of the applicability of the results under particular setting . The purpose of this paper is to introduce the development , basic principle , characteristics and application of PRECIS-2 for the design ers and decision makers when working on clinical trials In 2015 , YMCA-operated afterschool programs ( ASPs ) across South Carolina pledged to achieve the national st and ard that calls for every child to accumulate 30 min/day of moderate-to-vigorous physical activity ( MVPA ) during program time . This study shares the first-year findings related to the dissemination , implementation , and outcomes associated with the statewide intervention to achieve the MVPA St and ard . Twenty ASPs were sample d from all YMCA-operated ASPs ( N = 97 ) and visited at baseline ( spring 2015 ) and first-year follow-up ( spring 2016 ) . Programs were provided st and ardized professional development training to increase the MVPA children accumulated while attending ASPs . The training focused on extending the scheduled time for activity opportunities and modifying commonly played games to increase MVPA . The RE- AIM framework was used to evaluate the statewide intervention . Accelerometer-derived MVPA was the primary outcome . Implementation was evaluated via direct observation . Intent-to-treat ( ITT ) and as-treated comparisons were conducted in summer 2016 . Reach/adoption was variable , with attendance at trainings ranging from 0 to 100 % across ASPs . Effectiveness of the intervention using ITT models indicated no changes from baseline in the percentage of programs meeting the MVPA st and ard for boys or girls . Implementation levels also varied and were related to increases in both boys ’ and girls ’ MVPA for moderate and high implementers . Findings indicate improvements in MVPA can be made from attending the trainings and implementing some or all of the training components . Additional work is necessary to identify ways to ensure staff attend trainings to implement strategies and to identify which specific factors contributed to increases in MVPA There is currently a lot of interest in pilot studies conducted in preparation for r and omised controlled trials . This paper focuses on sample size requirements for external pilot studies for cluster r and omised trials . We consider how large an external pilot study needs to be to assess key parameters for input to the main trial sample size calculation when the primary outcome is continuous , and to estimate rates , for example recruitment rates , with reasonable precision . We used simulation to provide the distribution of the expected number of clusters for the main trial under different assumptions about the natural cluster size , intra-cluster correlation , eventual cluster size in the main trial , and various decisions made at the piloting stage . We chose intra-cluster correlation values and pilot study size to reflect those commonly reported in the literature . Our results show that estimates of sample size required for the main trial are likely to be biased downwards and very imprecise unless the pilot study includes large numbers of clusters and individual participants . We conclude that pilot studies will usually be too small to estimate parameters required for estimating a sample size for a main cluster r and omised trial ( e.g. the intra-cluster correlation coefficient ) with sufficient precision and too small to provide reliable estimates of rates for process measures such as recruitment or follow-up rates Background Many adolescent girls do not engage in sufficient physical activity ( PA ) . This study examined the feasibility of conducting a cluster r and omized controlled trial ( RCT ) to evaluate an after-school dance program to increase PA among 11–12 year old girls in Bristol , UK . Methods Three-arm , cluster RCT . Three secondary schools were assigned to intervention arm . Intervention participants received a 9-week dance program with 2 , 90-minute dance classes per week . Participants at 2 control schools received incentives for data collection . Participants at 2 additional control schools received incentives and a delayed dance workshop . Accelerometer data were collected at baseline ( time 0 ) , during the last week of the dance program ( time 1 ) and 20 weeks after the start of the study ( time 2 ) . Weekly attendance , enjoyment and perceived exertion were assessed in intervention participants . Post- study qualitative work was conducted with intervention participants and personnel . Results 40.1 % of girls provided consent to be in the study . The mean number of girls attending at least one dance session per week ranged from 15.4 to 25.9 . There was greater number of participants for whom accelerometer data were collected in control arms . The mean attendance was 13.3 sessions ( maximum = 18 ) . Perceived exertion ratings indicated that the girls did not find the sessions challenging . The dance teachers reported that the program content would benefit from revisions including less creative task time , a broader range of dance genres and improved behavioral management policies . At time 2 , the 95 % confidence intervals suggest between 5 and 12 minutes more weekday MVPA in the intervention group compared with the control incentives only group , and between 6 minutes fewer and 1 minute more compared with the control incentives plus workshop group . Between 14 and 24 schools would be required to detect a difference of 10 minutes in mean weekday MVPA between intervention and control groups . Conclusions It is possible to recruit 11–12 year old girls to participate in an after-school dance study . An after-school dance intervention has potential to positively affect the PA levels of 11–12 year old girls but an adequately powered RCT is required to test this intervention approach Background Screen-based activities , such as watching television ( TV ) , playing video games , and using computers , are common sedentary behaviors among young people and have been linked with increased energy intake and overweight . Previous home-based sedentary behaviour interventions have been limited by focusing primarily on the child , small sample sizes , and short follow-up periods . The SWITCH ( Screen-Time Weight-loss Intervention Targeting Children at Home ) study aim ed to determine the effect of a home-based , family-delivered intervention to reduce screen-based sedentary behaviour on body composition , sedentary behaviour , physical activity , and diet over 24 weeks in overweight and obese children . Methods A two-arm , parallel , r and omized controlled trial was conducted . Children and their primary caregiver living in Auckl and , New Zeal and were recruited via schools , community centres , and word of mouth . The intervention , delivered over 20 weeks , consisted of a face-to-face meeting with the parent/caregiver and the child to deliver intervention content , which focused on training and educating them to use a wide range of strategies design ed to reduce their child ’s screen time . Families were given Time Machine TV monitoring devices to assist with allocating screen time , activity packages to promote alternative activities , online support via a website , and monthly newsletters . Control participants were given the intervention material on completion of follow-up . The primary outcome was change in children ’s BMI z-score from baseline to 24 weeks . Results Children ( n = 251 ) aged 9 - 12 years and their primary caregiver were r and omized to receive the SWITCH intervention ( n = 127 ) or no intervention ( controls ; n = 124 ) . There was no significant difference in change of z BMI between the intervention and control groups , although a favorable trend was observed ( -0.016 ; 95 % CI : -0.084 , 0.051 ; p = 0.64 ) . There were also no significant differences on secondary outcomes , except for a trend towards increased children ’s moderate intensity physical activity in the intervention group ( 24.3 min/d ; 95 % CI : -0.94 , 49.51 ; p = 0.06 ) . Conclusions A home-based , family-delivered intervention to reduce all leisure-time screen use had no significant effect on screen-time or on BMI at 24 weeks in overweight and obese children aged 9 - 12 years . Trial registration Australian New Zeal and Clinical Trials RegistryWebsite : http://www.anzctr.org.auTrial registration number : Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials OBJECTIVE To test a 2-year community- and family-based obesity prevention program for low-income African American girls : Stanford GEMS ( Girls ' health Enrichment Multi-site Studies ) . DESIGN R and omized controlled trial with follow-up measures scheduled at 6 , 12 , 18 , and 24 months . SETTING Low-income areas of Oakl and , California . PARTICIPANTS African American girls aged 8 to 10 years ( N=261 ) and their parents or guardians . INTERVENTIONS Families were r and omized to one of two 2-year , culturally tailored interventions : ( 1 ) after-school hip-hop , African , and step dance classes and a home/family-based intervention to reduce screen media use or ( 2 ) information-based health education . MAIN OUTCOME MEASURE Changes in body mass index ( BMI ) . RESULTS Changes in BMI did not differ between groups ( adjusted mean difference [ 95 % confidence interval ] = 0.04 [ -0.18 to 0.27 ] per year ) . Among secondary outcomes , fasting total cholesterol level ( adjusted mean difference , -3.49 [ 95 % confidence interval , -5.28 to -1.70 ] mg/dL per year ) , low-density lipoprotein cholesterol level ( -3.02 [ -4.74 to -1.31 ] mg/dL per year ) , incidence of hyperinsulinemia ( relative risk , 0.35 [ 0.13 to 0.93 ] ) , and depressive symptoms ( -0.21 [ -0.42 to -0.001 ] per year ) decreased more among girls in the dance and screen time reduction intervention . In exploratory moderator analysis , the dance and screen time reduction intervention slowed BMI gain more than health education among girls who watched more television at baseline ( P = .02 ) and /or those whose parents or guardians were unmarried ( P = .01 ) . CONCLUSIONS A culturally tailored after-school dance and screen time reduction intervention for low-income , preadolescent African American girls did not significantly reduce BMI gain compared with health education but did produce potentially clinical ly important reductions in lipid levels , hyperinsulinemia , and depressive symptoms . There was also evidence for greater effectiveness in high-risk subgroups of girls Background : The best outcomes for treating childhood obesity have come from comprehensive family-based programmes . However there are questions over their generalizability . Objective : To examine the acceptability and effectiveness of ‘ family-based behavioural treatment ’ ( FBBT ) for childhood obesity in an ethnically and socially diverse sample of families in a UK National Health Service ( NHS ) setting . Methods : In this parallel group , r and omized controlled trial , 72 obese children were r and omized to FBBT or a waiting-list control . Primary outcomes were body mass index ( BMI ) and BMI s.d . scores ( SDSs ) . Secondary outcomes were weight , weight SDSs , height , height SDSs , waist , waist SDSs , FM index , FFM index , blood pressure ( BP ) and psychosocial measures . The outcomes were assessed at baseline and after treatment , with analyses of 6-month data performed on an intent-to-treat ( ITT ) basis . Follow-up anthropometric data were collected at 12 months for the treatment group . Results : ITT analyses included all children with baseline data ( n=60 ) . There were significant BMI SDS changes ( P<0.01 ) for the treatment and control groups of −0.11 ( 0.16 ) and −0.10 ( 1.6 ) . The treatment group showed a significant reduction in systolic BP ( −0.24 ( 0.7 ) , P<0.05 ) and improvements in quality of life and eating attitudes ( P<0.05 ) , with no significant changes for the control group . However the between-group treatment effects for BMI , body composition , BP and psychosocial outcomes were not significant . There was no overall change in BMI or BMI SDSs from 0–12 months for the treatment group . No adverse effects were reported . Conclusions : Both treatment and control groups experienced significant reductions in the level of overweight , but with no significant difference between them . There were no significant group differences for any of the secondary outcomes . This trial was registered at http://www.controlled-trials.com/ under IS RCT N 51382628 Objective To investigate the effectiveness of a school based intervention to increase physical activity , reduce sedentary behaviour , and increase fruit and vegetable consumption in children . Design Cluster r and omised controlled trial . Setting 60 primary schools in the south west of Engl and . Participants Primary school children who were in school year 4 ( age 8 - 9 years ) at recruitment and baseline assessment , in year 5 during the intervention , and at the end of year 5 ( age 9 - 10 ) at follow-up assessment . Intervention The Active for Life Year 5 ( AFLY5 ) intervention consisted of teacher training , provision of lesson and child-parent interactive homework plans , all material s required for lessons and homework , and written material s for school newsletters and parents . The intervention was delivered when children were in school year 5 ( age 9 - 10 years ) . Schools allocated to control received st and ard teaching . Main outcome measures The pre-specified primary outcomes were accelerometer assessed minutes of moderate to vigorous physical activity per day , accelerometer assessed minutes of sedentary behaviour per day , and reported daily consumption of servings of fruit and vegetables . Results 60 schools with more than 2221 children were recruited ; valid data were available for fruit and vegetable consumption for 2121 children , for accelerometer assessed physical activity and sedentary behaviour for 1252 children , and for secondary outcomes for between 1825 and 2212 children for the main analyses . None of the three primary outcomes differed between children in schools allocated to the AFLY5 intervention and those allocated to the control group . The difference in means comparing the intervention group with the control group was –1.35 ( 95 % confidence interval –5.29 to 2.59 ) minutes per day for moderate to vigorous physical activity , –0.11 ( –9.71 to 9.49 ) minutes per day for sedentary behaviour , and 0.08 ( –0.12 to 0.28 ) servings per day for fruit and vegetable consumption . The intervention was effective for three out of nine of the secondary outcomes after multiple testing was taken into account : self reported time spent in screen viewing at the weekend ( –21 ( –37 to –4 ) minutes per day ) , self reported servings of snacks per day ( –0.22 ( –0.38 to –0.05 ) ) , and servings of high energy drinks per day ( –0.26 ( –0.43 to –0.10 ) ) were all reduced . Results from a series of sensitivity analyses testing different assumptions about missing data and from per protocol analyses produced similar results . Conclusion The findings suggest that the AFLY5 school based intervention is not effective at increasing levels of physical activity , decreasing sedentary behaviour , and increasing fruit and vegetable consumption in primary school children . Change in these activities may require more intensive behavioural interventions with children or upstream interventions at the family and societal level , as well as at the school environment level . These findings have relevance for research ers , policy makers , public health practitioners , and doctors who are involved in health promotion , policy making , and commissioning services . Trial registration Current Controlled Trials IS RCT N50133740 Objective : Physical activity associates with mental health and neurocognitive function , showing potential for addressing ADHD symptoms . As a preliminary assessment of this potential , the authors piloted a before-school physical activity intervention for young children . Method : Seventeen children ( Grade s K-3 ) exhibiting four or more hyperactivity/impulsivity symptoms on the Disruptive Behavior Disorders Rating Scale ( Pelham , 2002 ) completed about 26 min of continuous moderate-to-vigorous physical activity daily over eight school weeks . The authors administered cognitive , motor , social , and behavioral functioning measures at pre- and postprogram , assessed response inhibition weekly , and coded negative behaviors daily . Results : Several measures showed significant or marginally significant change over time ( effect size = 0.35 - 0.96 ) with additional measures showing meaningful effect size values ( ≥ 0.20 ) . Response inhibition effects were most consistent . Most participants ( 64 % to 71 % ) exhibited overall improvement according to postprogram parent , teacher , and program staff ratings . Conclusion : Physical activity shows promise for addressing ADHD symptoms in young children Background The HEALTHY study was design ed to respond to the alarming trends in increasing rates of overweight , obesity , and type 2 diabetes mellitus in youth . The objective of this analysis was to examine the effects of the HEALTHY study on student self-reported dietary intakes ( energy , macronutrients and grams consumed of selected food groups ) . Methods HEALTHY was a cluster-r and omized study in 42 public middle schools . Students , n = 3908 , self-reported dietary intake using the Block Kids Question naire . General linear mixed models were used to analyze differences in dietary intake at the end of the study between intervention and control schools . Results The reported average daily fruit consumption was 10 % higher at the end of the study in the intervention schools than in the control schools ( 138 g or approximately 2 servings versus 122 g , respectively , p = 0.0016 ) . The reported water intake was approximately 2 fluid ounces higher in the intervention schools than in the control ( 483 g versus 429 g respectively ; p = 0.008 ) . There were no significant differences between intervention and control for mean intakes of energy , macronutrients , fiber , grains , vegetables , legumes , sweets , sweetened beverages , and higher- or lower-fat milk consumption . Conclusion The HEALTHY study , a five-semester middle school-based intervention program that integrated multiple components in nutrition , physical education , behavior change , and social marketing-based communications , result ed in significant changes to student 's reported fruit and water intake . Subsequent interventions need to go beyond the school environment to change diet behaviors that may affect weight status of children . Clinical Trials Registration The aim of this study was to assess the feasibility , acceptability and potential efficacy of a physical activity program for preschool children . A 20-week , 2-arm parallel cluster r and omized controlled pilot trial was conducted . The intervention comprised structured activities for children and professional development for staff . The control group participated in usual care activities , which included design ated inside and outside playtime . Primary outcomes were movement skill development and objective ly measured physical activity . At follow-up , compared with children in the control group , children in the intervention group showed greater improvements in movement skill proficiency , with this improvement statically significant for overall movement skill development ( adjust diff . = 2.08 , 95 % CI 0.76 , 3.40 ; Cohen 's d = 0.47 ) and significantly greater increases in objective ly measured physical activity ( counts per minute ) during the preschool day ( adjust diff . = 110.5 , 95 % CI 33.6 , 187.3 ; Cohen 's d = 0.46 ) . This study demonstrates that a physical activity program implemented by staff within a preschool setting is feasible , acceptable and potentially efficacious We describe a framework for defining pilot and feasibility studies focusing on studies conducted in preparation for a r and omised controlled trial . To develop the framework , we undertook a Delphi survey ; ran an open meeting at a trial methodology conference ; conducted a review of definitions outside the health research context ; consulted experts at an international consensus meeting ; and review ed 27 empirical pilot or feasibility studies . We initially adopted mutually exclusive definitions of pilot and feasibility studies . However , some Delphi survey respondents and the majority of open meeting attendees disagreed with the idea of mutually exclusive definitions . Their viewpoint was supported by definitions outside the health research context , the use of the terms ‘ pilot ’ and ‘ feasibility ’ in the literature , and participants at the international consensus meeting . In our framework , pilot studies are a subset of feasibility studies , rather than the two being mutually exclusive . A feasibility study asks whether something can be done , should we proceed with it , and if so , how . A pilot study asks the same questions but also has a specific design feature : in a pilot study a future study , or part of a future study , is conducted on a smaller scale . We suggest that to facilitate their identification , these studies should be clearly identified using the terms ‘ feasibility ’ or ‘ pilot ’ as appropriate . This should include feasibility studies that are largely qualitative ; we found these difficult to identify in electronic search es because research ers rarely used the term ‘ feasibility ’ in the title or abstract of such studies . Investigators should also report appropriate objectives and methods related to feasibility ; and give clear confirmation that their study is in preparation for a future r and omised controlled trial design ed to assess the effect of an intervention OBJECTIVE To evaluate the impact of a multifaceted , school-based intervention on inner city youth at high risk for type 2 diabetes mellitus ( T2DM ) and to determine whether the addition of coping skills training ( CST ) and health coaching improves outcomes . METHOD 198 students in New Haven , CT at risk for T2DM ( BMI > 85th percentile and family history of diabetes ) were r and omized by school to an educational intervention with or without the addition of CST and health coaching . Students were enrolled from 2004 to 2007 and followed for 12 months . RESULTS Students in both groups showed some improvement in anthropometric measures , lipids , and depressive symptoms over 12 months . BMI was not improved by the intervention . Students who received CST showed greater improvement on some indicators of metabolic risk than students who received education only . CONCLUSION A multifaceted , school-based intervention may hold promise for reducing metabolic risk in urban , minority youth Background Slowing the decline in participation in physical activity among adolescent girls is a public health priority . This study reports the outcomes from a multi-component school-based intervention ( Girls in Sport ) , focused on promoting physical activity among adolescent girls . Methods Group r and omized controlled trial in 24 secondary schools ( 12 intervention and 12 control ) . Assessment s were conducted at baseline ( 2009 ) and at 18 months post-baseline ( 2010 ) . The setting was secondary schools in urban , regional and rural areas of New South Wales , Australia . All girls in Grade 8 in 2009 who attended these schools were invited to participate in the study ( N = 1769 ) . Using a Health Promoting Schools and Action Learning Frameworks , each school formed a committee and developed an action plan for promoting physical activity among Grade 8 girls . The action plan incorporated strategies in three main areas – i ) the formal curriculum , ii ) school environment , and iii ) home/school/community links – based on the results of formative data from target girls and staff and on individual needs of the school . A member of the research team supported each school throughout the intervention . The main outcome measure was accelerometer-derived total physical activity ( TPA ) spent in physical activity . Data were analyzed from December 2011 to March 2012 . Results 1518 girls ( mean age 13.6y ±0.02 ) were assessed at baseline . There was a significant decline in TPA from baseline to 18-month follow-up with no differences between girls in the intervention and control schools . Only one-third of schools ( 4/12 ) implemented the intervention as per their action plan . Per- protocol analyses on these schools revealed a smaller decline in percentage of time spent in MVPA among girls in the intervention group ( adjusted difference 0.5 % , 95 % CI = -0.01 , 0.99 , P = 0.05 ) . Conclusions The Girls in Sport intervention was not effective in reducing the decline in physical activity among adolescent girls . Lack of implementation by most intervention schools was the main reason for a null effect . Identifying strategies to enhance implementation levels is critical to determining the true potential of this intervention approach . Trial registration This study was retrospectively registered with the Australian New Zeal and Clinical Trials Registry ACTRN12610001077055 . Date of registration : 7 December 2010 OBJECTIVE To assess the feasibility , acceptability , and outcomes of 2 versions of a culturally relevant , family-based intervention to prevent excess weight gain in pre-adolescent African-American girls . DESIGN Three-arm , 12-week parallel group r and omized controlled pilot trial . SETTING Community centers in Memphis , Tennessee . PARTICIPANTS Sixty African-American girls , aged 8 to 10 years , with a body mass index ( BMI ) > or = 25th percentile of the CDC growth charts , along with their parents/caregivers . INTERVENTIONS The active interventions involved highly interactive weekly group sessions with either girls ( child-targeted program ) or parents/caregivers ( parent-targeted program ) . Content focused on knowledge and behavior change skills to promote healthy eating and increased physical activity . The comparison intervention focused on global self-esteem . MAIN OUTCOME MEASURES Given the lack of power and the limited time frame of the pilot study , outcomes were evaluated on the basis of implementation measures and changes in physical activity ( accelerometer data ) , and in consumption of sweetened beverages and water , as estimated from question naires . Changes in body mass index , waist circumference , and body composition were also examined . RESULTS The Memphis GEMS pilot intervention met all recruitment , retention , implementation , and participation goals , and was given high rating by both participants and interventionists . With respect to the comparison intervention , girls in both the child-targeted and parent-targeted interventions demonstrated a trend toward reduced body mass index and waist circumference . In addition , girls in the active intervention groups reduced their consumption of sweetened beverages by 34 % , increased their level of moderate-to-vigorous activity by 12 % , and increased their serving ; of water by 1.5 % . CONCLUSIONS The findings from this pilot study demonstrated the feasibility , perceived acceptability , and efficacy of culturally relevant , obesity prevention interventions for pre-adolescent African-American girls and their parents/caregivers Abstract Background Few school-based interventions have been successful in reducing physical activity decline and preventing overweight and obesity in adolescent population s. As a result , few cost effectiveness analyses have been reported . The aim of this paper is to report the cost and cost effectiveness of the Physical Activity 4 Everyone ( PA4E1 ) intervention which was a multi-component intervention implemented in secondary schools located in low-income communities . Cost effectiveness was assessed using both the physical activity and weight status trial outcomes . Methods Intervention and Study Design : The PA4E1 cluster r and omised controlled trial was implemented in 10 Australian secondary schools ( 5 intervention : 5 control ) and consisted of intervention schools receiving seven physical activity promotion strategies and six additional strategies that supported school implementation of the intervention components . Costs associated with physical activity strategies , and intervention implementation strategies within the five intervention schools were estimated and compared to the costs of usual physical activity practice s of schools in the control group . The total cost of implementing the intervention was estimated from a societal perspective , based on the number of enrolled students in the target grade at the start of the intervention ( Grade 7 , n = 837 ) . Economic Outcomes : The economic analysis outcomes were cost and incremental cost effectiveness ratios for the following : minutes of moderate-to-vigorous physical activity ( MVPA ) per day gained , MET hours gained per person/day ; Body Mass Index ( BMI ) unit avoided ; and 10 % reduction in BMI z-score . Results The intervention cost AUD $ 329,952 over 24 months , or AUD$394 per student in the intervention group . This result ed in a cost effectiveness ratio of AUD$56 ( $ 35–$147 ) per additional minute of MVPA , AUD$1 ( $ 0.6–$2.7 ) per MET hour gained per person per day , AUD$1408 ( $ 788–$6,570 ) per BMI unit avoided , and AUD$563 ( $ 282–$3,942 ) per 10 % reduction in BMI z-score . Conclusion PA4E1 is a cost effective intervention for increasing the physical activity levels and reducing unhealthy weight gain in adolescence , a period in which physical activity typically declines . Additional modelling could explore the potential economic impact of the intervention on morbidity and mortality . Trial registration Australian New Zeal and Clinical Trials Registry ACTRN12612000382875 Background There is little published guidance as to the sample size required for a pilot or feasibility trial despite the fact that a sample size justification is a key element in the design of a trial . A sample size justification should give the minimum number of participants needed in order to meet the objectives of the trial . This paper seeks to describe the target sample sizes set for pilot and feasibility r and omised controlled trials , currently running within the United Kingdom . Methods Data were gathered from the United Kingdom Clinical Research Network ( UKCRN ) data base using the search terms ‘ pilot ’ and ‘ feasibility ’ . From this search 513 studies were assessed for eligibility of which 79 met the inclusion criteria . Where the data summary on the UKCRN Data base was incomplete , data were also gathered from : the International St and ardised R and omised Controlled Trial Number ( IS RCT N ) register ; the clinical trials.gov website and the website of the funders . For 62 of the trials , it was necessary to contact members of the research team by email to ensure completeness . Results Of the 79 trials analysed , 50 ( 63.3 % ) were labelled as pilot trials , 25 ( 31.6 % ) feasibility and 14 were described as both pilot and feasibility trials . The majority had two arms ( n = 68 , 86.1 % ) and the two most common endpoints were continuous ( n = 45 , 57.0 % ) and dichotomous ( n = 31 , 39.2 % ) . Pilot trials were found to have a smaller sample size per arm ( median = 30 , range = 8 to 114 participants ) than feasibility trials ( median = 36 , range = 10 to 300 participants ) . By type of endpoint , across feasibility and pilot trials , the median sample size per arm was 36 ( range = 10 to 300 participants ) for trials with a dichotomous endpoint and 30 ( range = 8 to 114 participants ) for trials with a continuous endpoint . Publicly funded pilot trials appear to be larger than industry funded pilot trials : median sample sizes of 33 ( range = 15 to 114 participants ) and 25 ( range = 8 to 100 participants ) respectively . Conclusion All studies should have a sample size justification . Not all studies however need to have a sample size calculation . For pilot and feasibility trials , while a sample size justification is important , a formal sample size calculation may not be appropriate . The results in this paper describe the observed sample sizes in feasibility and pilot r and omised controlled trials on the UKCRN Data base 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 OBJECTIVES To determine whether a large-scale physical activity intervention could affect body composition in primary school students in Beijing , China . METHODS The study design was one-year cluster r and omized controlled trial of physical activity intervention ( 20 min of daily exercise in the classroom ) with an additional year of follow-up among 4 700 students aged 8 - 11 years at baseline . RESULTS After the one-year intervention , BMI increased by 0.56 kg/m(2 ) ( SD 1.15 ) in the intervention group and by 0.72 kg/m(2 ) ( SD 1.20 ) in the control group , with a mean difference of -0.15 kg/m(2 ) ( 95 % CI : -0.28 to -0.02 ) . BMI z score decreased by -0.05 ( SD 0.44 ) in the intervention group , but increased by 0.01 ( SD 0.46 ) in the control group , with a mean difference of -0.07 ( -0.13 to -0.01 ) . After another year of follow up , compared to the control group , children in the intervention group had significantly lower BMI ( -0.13 , -0.25 to -0.01 ) , BMI z score ( -0.05 , -0.10 to -0.01 ) , fat mass ( -0.27 kg , -0.53 to -0.02 ) and percent body fat ( -0.53 , -1.00 to -0.05 ) . The intervention had a more pronounced effect on weight , height , BMI , BMI z score , and body composition among obese children than among normal weight or overweight children . Compared to the control group , the intervention group had a significantly higher percentage of children who maintained or reduced their BMI z score at year 1 ( P=0.008 ) and year 2 ( P=0.04 ) . CONCLUSIONS These findings suggest that 20 min of daily moderate to vigorous physical activity during the school year is a feasible and effective way to prevent excessive gain of body weight , BMI , and body fatness in primary school students More than 20 % of US children between ages 2 and 5 years are overweight suggesting efforts to prevent obesity must begin earlier . This study tested the independent and combined effects of two behavioral interventions delivered to parents , design ed to promote healthy infant growth in the first year . Mother-newborn dyads intending to breastfeed were recruited from a maternity ward . With a 2 × 2 design , 160 dyads were r and omized into one of four treatment cells to receive both , one , or no interventions delivered at two nurse home visits . The first intervention ( " Soothe/Sleep " ) instructed parents on discriminating between hunger and other sources of infant distress . Soothing strategies were taught to minimize feeding for non-hunger-related fussiness and to prolong sleep duration , particularly at night . The second intervention ( " Introduction of Solids " ) taught parents about hunger and satiety cues , the timing for the introduction of solid foods , and how to overcome infants ' initial rejection of healthy foods through repeated exposure . A total of 110 mother-infant dyads completed the year-long study . At 1 year , infants who received both interventions had lower weight-for-length percentiles ( P = 0.009 ) . Participants receiving both interventions had a mean weight-for-length in the 33rd percentile ; in contrast , those in other study groups were higher first intervention only--50th percentile ; second intervention only--56th percentile ; control group--50th percentile).This suggests that multicomponent behavioral interventions may have potential for long-term obesity prevention ( Clinical Trials.gov number , NCT00359242 ) The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement is a guideline design ed to improve the transparency and quality of the reporting of r and omised controlled trials ( RCTs ) . In this article we present an extension to that statement for r and omised pilot and feasibility trials conducted in advance of a future definitive RCT . The checklist applies to any r and omised study in which a future definitive RCT , or part of it , is conducted on a smaller scale , regardless of its design ( eg , cluster , factorial , crossover ) or the terms used by authors to describe the study ( eg , pilot , feasibility , trial , study ) . The extension does not directly apply to internal pilot studies built into the design of a main trial , non-r and omised pilot and feasibility studies , or phase II studies , but these studies all have some similarities to r and omised pilot and feasibility studies and so many of the principles might also apply . The development of the extension was motivated by the growing number of studies described as feasibility or pilot studies and by research that has identified weaknesses in their reporting and conduct . We followed recommended good practice to develop the extension , including carrying out a Delphi survey , holding a consensus meeting and research team meetings , and piloting the checklist . The aims and objectives of pilot and feasibility r and omised studies differ from those of other r and omised trials . Consequently , although much of the information to be reported in these trials is similar to those in r and omised controlled trials ( RCTs ) assessing effectiveness and efficacy , there are some key differences in the type of information and in the appropriate interpretation of st and ard CONSORT reporting items . We have retained some of the original CONSORT statement items , but most have been adapted , some removed , and new items added . The new items cover how participants were identified and consent obtained ; if applicable , the prespecified criteria used to judge whether or how to proceed with a future definitive RCT ; if relevant , other important unintended consequences ; implication s for progression from pilot to future definitive RCT , including any proposed amendments ; and ethical approval or approval by a research review committee confirmed with a reference number . This article includes the 26 item checklist , a separate checklist for the abstract , a template for a CONSORT flowchart for these studies , and an explanation of the changes made and supporting examples . We believe that routine use of this proposed extension to the CONSORT statement will result in improvements in the reporting of pilot trials . Editor ’s note : In order to encourage its wide dissemination this article is freely accessible on the BMJ and Pilot and Feasibility Studies journal websites In the past few decades , prevention scientists have developed and tested a range of interventions with demonstrated benefits on child and adolescent cognitive , affective , and behavioral health . These evidence -based interventions offer promise of population -level benefit if accompanied by findings of implementation science to facilitate adoption , widespread implementation , and sustainment . Though there have been notable examples of successful efforts to scale up interventions , more work is needed to optimize benefit . Although the traditional pathway from intervention development and testing to implementation has served the research community well-allowing for a systematic advance of evidence -based interventions that appear ready for implementation-progress has been limited by maintaining the hypothesis that evidence generation must be complete prior to implementation . This sets up the challenging dichotomy between fidelity and adaptation and limits the science of adaptation to findings from r and omized trials of adapted interventions . The field can do better . This paper argues for the development of strategies to advance the science of adaptation in the context of implementation that would more comprehensively describe the needed fit between interventions and their setting s , and embrace opportunities for ongoing learning about optimal intervention delivery over time . Efforts to build the result ing adaptome ( pronounced " adapt-ohm " ) will include the construction of a common data platform to house systematic ally captured information about variations in delivery of evidence -based interventions across multiple population s and context s , and provide feedback to intervention developers , as well as the implementation research and practice communities . Finally , the article identifies next steps to jumpstart adaptome data platform development The goal of this study was to compare the effects of before school physical activity ( PA ) and sedentary classroom-based ( SC ) interventions on the symptoms , behavior , moodiness , and peer functioning of young children ( Mage = 6.83 ) at risk for attention-deficit/hyperactivity disorder ( ADHD-risk ; n = 94 ) and typically developing children ( TD ; n = 108 ) . Children were r and omly assigned to either PA or SC and participated in the assigned intervention 31 min per day , each school day , over the course of 12 weeks . Parent and teacher ratings of ADHD symptoms ( inattention , hyperactivity/impulsivity ) , oppositional behavior , moodiness , behavior toward peers , and reputation with peers , were used as dependent variables . Primary analyses indicate that the PA intervention was more effective than the SC intervention at reducing inattention and moodiness in the home context . Less conservative follow-up analyses within ADHD status and intervention groups suggest that a PA intervention may reduce impairment associated with ADHD-risk in both home and school domains ; interpretive caution is warranted , however , given the liberal approach to these analyses . Unexpectedly , these findings also indicate the potential utility of a before school SC intervention as a tool for managing ADHD symptoms . Inclusion of a no treatment control group in future studies will enable further underst and ing of PA as an alternative management strategy for ADHD symptoms Objectives To assess the behavioural and weight status outcomes in English children in a feasibility study of a novel primary school-based obesity prevention programme . Design Exploratory cluster r and omised controlled trial of the Healthy Lifestyles Programme . Setting Four city primary schools ( two control and two intervention ) in the South West of Engl and . Participants 202 children aged 9–10 years , of whom 193 and 188 were followed up at 18 and 24 months , respectively . No child was excluded from the study ; however , to be eligible , schools were required to have at least one single Year 5 class . Intervention Four-phase multicomponent programme using a range of school-based activities including lessons , assemblies , parents ' evenings , interactive drama workshops and goal setting to engage and support schools , children and their families in healthy lifestyle behaviours . It runs over the spring and summer term of Year 5 and the autumn term of Year 6 . Primary and secondary outcomes Weight status outcomes were body mass index , waist circumference and body fat st and ard deviation scores ( SDS ) at 18 and 24 months , and behavioural outcomes were physical activity , television ( TV ) viewing/screen time and food intake at 18 months . Results At 18 months of follow-up , intervention children consumed less energy-dense snacks and more healthy snacks ; had less ‘ negative food markers ’ , more ‘ positive food markers ’ , lower mean TV/screen time and spent more time doing moderate-vigorous physical activity each day than those in the control schools . Intervention children had lower anthropometric measures at 18 and 24 months than control children , with larger differences at 24 months than at 18 months for nearly all measures . Conclusions Results from this exploratory trial show consistent positive changes in favour of the intervention across all targeted behaviours , which , in turn , appear to affect weight status and body shape . A definitive trial is now justified Objective . To evaluate the effectiveness of a 12-month multicomponent obesity prevention intervention . Setting . 9 elementary schools in Santiago , Chile . Subjects . 6–8 y old low-income children ( N = 1474 ) . Design . R and omized controlled study ; 5 intervention/4 control schools . We trained teachers to deliver nutrition contents and improve the quality of PE classes . We determined % healthy snacks brought from home , children 's nutrition knowledge , nutritional status , duration of PE classes , and % time in moderate/vigorous activity ( MVA ) . Effectiveness was determined by comparing Δ BMI Z between intervention and control children using PROCMIXED . Results . % obesity increased in boys from both types of schools and in girls from control schools , while decreasing in girls from intervention schools ( all nonsignificant ) . % class time in MVA declined ( 24.5–16.2 ) while remaining unchanged ( 24.8–23.7 % ) in classes conducted by untrained and trained teachers , respectively . In boys , BMI Z declined ( 1.33–1.24 ) and increased ( 1.22–1.35 ) in intervention and control schools , respectively . In girls , BMI Z remained unchanged in intervention schools , while increasing significantly in control schools ( 0.91–1.06 , P = 0.024 ) . Interaction group ∗ time was significant for boys ( P < 0.0001 ) and girls ( P = 0.004 ) . Conclusions . This intervention was effective in controlling obesity , but not preventing it . Even though impact was small , results showed that when no intervention is implemented , obesity increases Background The aim of this study was to examine the effectiveness and cost of an after-school dance intervention at increasing the physical activity levels of Year 7 girls ( age 11–12 ) . Methods A cluster r and omised controlled trial was conducted in 18 secondary schools . Participants were Year 7 girls attending a study school . The Bristol Girls Dance Project ( BGDP ) intervention consisted of up to forty , 75-minute dance sessions delivered in the period immediately after school by experienced dance instructors over 20-weeks . The pre-specified primary outcome was accelerometer assessed mean minutes of weekday moderate to vigorous physical activity ( MVPA ) at time 2 ( 52 weeks are T0 baseline assessment s ) . Secondary outcomes included accelerometer assessed mean minutes of weekday MVPA at time 1 ( while the intervention was still running ) and psychosocial outcomes . Intervention costs were assessed . Results 571 girls participated . Valid accelerometer data were collected from 549 girls at baseline with 508 girls providing valid accelerometer data at baseline and time 2 . There were no differences between the intervention and control group for accelerometer assessed physical activity at either time 1 or time 2 . Only one third of the girls in the intervention arm met the pre-set adherence criteria of attending two thirds of the dance sessions that were available to them . Instrumental variable regression analyses using complier average causal effects provided no evidence of a difference between girls who attended the sessions and the control group . The average cost of the intervention was £ 73 per girl , which was reduced to £ 63 when dance instructor travel expenses were excluded . Conclusion This trial showed no evidence that an after-school dance programme can increase the physical activity of Year 7 girls . The trial highlighted the difficulty encountered in maintaining attendance in physical activity programmes delivered in secondary schools . There is a need to find new ways to help adolescent girls to be physically active via identifying ways to support and encourage sustained engagement in physical activity over the life course . Trial registration IS RCT Pilot studies play an important role in health research , but they can be misused , mistreated and misrepresented . In this paper we focus on pilot studies that are used specifically to plan a r and omized controlled trial ( RCT ) . Citing examples from the literature , we provide a method ological framework in which to work , and discuss reasons why a pilot study might be undertaken . A well-conducted pilot study , giving a clear list of aims and objectives within a formal framework will encourage method ological rigour , ensure that the work is scientifically valid and publishable , and will lead to higher quality RCTs . It will also safeguard against pilot studies being conducted simply because of small numbers of available patients Objective To assess whether a physical activity intervention reduces body mass index in young children . Design Cluster r and omised controlled single blinded trial over 12 months . Setting Thirty six nurseries in Glasgow , Scotl and . Participants 545 children in their preschool year , mean age 4.2 years ( SD 0.2 ) at baseline . Intervention Enhanced physical activity programme in nursery ( three 30 minute sessions a week over 24 weeks ) plus home based health education aim ed at increasing physical activity through play and reducing sedentary behaviour . Main outcome measure Body mass index , expressed as a st and ard deviation score relative to UK 1990 reference data . Secondary measures were objective ly measured physical activity and sedentary behaviour ; fundamental movement skills ; and evaluation of the process . Results Group allocation had no significant effect on the primary outcome measure at six and 12 months or on measures of physical activity and sedentary behaviour by accelerometry . Children in the intervention group had significantly higher performance in movement skills tests than control children at six month follow-up ( P=0.0027 ; 95 % confidence interval 0.3 to 1.3 ) after adjustment for sex and baseline performance . Conclusions Physical activity can significantly improve motor skills but did not reduce body mass index in young children in this trial . Trial registration Current Controlled Trials IS RCT N36363490 The primary objective of this pilot study was to evaluate the effect of active video games on children 's physical activity levels . Twenty children ( mean ± SD age = 12 ± 1.5 years ; 40 % female ) were r and omised to receive either an active video game up grade package or to a control group ( no intervention ) . Effects on physical activity over the 12-week intervention period were measured using objective ( Actigraph accelerometer ) and subjective ( Physical Activity Question naire for Children [ PAQ-C ] ) measures . An activity log was used to estimate time spent playing active and non-active video games . Children in the intervention group spent less mean time over the total 12-week intervention period playing all video games compared to those in the control group ( 54 versus 98 minutes/day [ difference = -44 minutes/day , 95 % CI [ -92 , 2 ] ] , p = 0.06 ) . Average time spent in all physical activities measured with an accelerometer was higher in the active video game intervention group compared to the control group ( difference at 6 weeks = 194 counts/min , p = 0.04 , and at 12 weeks = 48 counts/min , p = 0.06).This preliminary study suggests that playing active video games on a regular basis may have positive effects on children 's overall physical activity levels . Further research is needed to confirm if playing these games over a longer period of time could also have positive effects on children 's body weight and body mass index . Trial Registration Background and purpose A behavioral intervention is a program aim ed at modifying behavior for the purpose of treating or preventing disease , promoting health , and /or enhancing well-being . Many behavioral interventions are dynamic treatment regimens , that is , sequential , individualized multicomponent interventions in which the intensity and /or type of treatment is varied in response to the needs and progress of the individual participant . The multiphase optimization strategy ( MOST ) is a comprehensive framework for development , optimization , and evaluation of behavioral interventions , including dynamic treatment regimens . The objective of optimization is to make dynamic treatment regimens more effective , efficient , scalable , and sustainable . An important tool for optimization of dynamic treatment regimens is the sequential , multiple assignment , r and omized trial ( SMART ) . The purpose of this article is to discuss how to develop optimized dynamic treatment regimens within the MOST framework . Methods and results The article discusses the preparation , optimization , and evaluation phases of MOST . It is shown how MOST can be used to develop a dynamic treatment regimen to meet a prespecified optimization criterion . The SMART is an efficient experimental design for gathering the information needed to optimize a dynamic treatment regimen within MOST . One signature feature of the SMART is that r and omization takes place at more than one point in time . Conclusion MOST and SMART can be used to develop optimized dynamic treatment regimens that will have a greater public health impact Introduction Lifestyle Triple P is a general parenting intervention which focuses on preventing further excessive weight gain in overweight and obese children . The objective of the current study was to assess the effectiveness of the Lifestyle Triple P intervention in the Netherl and s. Method We used a parallel r and omized controlled design to test the effectiveness of the intervention . In total , 86 child-parent triads ( children 4–8 years old , overweight or obese ) were recruited and r and omly assigned ( allocation ratio 1:1 ) to the Lifestyle Triple P intervention or the control condition . Parents in the intervention condition received a 14-week intervention consisting of ten 90-minute group sessions and four individual telephone sessions . Primary outcome measure was the children ’s body composition ( BMI z-scores , waist circumference and skinfolds ) . The research assistant who performed the measurements was blinded for group assignment . Secondary outcome measures were the children ’s dietary behavior and physical activity level , parenting practice s , parental feeding style , parenting style , and parental self-efficacy . Outcome measures were assessed at baseline and 4 months ( short-term ) and 12 months ( long-term ) after baseline . Multilevel multiple regression analyses were conducted to determine the effect of the intervention on primary and secondary outcome measures . Results No intervention effects were found on children ’s body composition . Analyses of secondary outcomes showed positive short-term intervention effects on children ’s soft-drink consumption and parental responsibility regarding physical activity , encouragement to eat , psychological control , and efficacy and satisfaction with parenting . Longer-term intervention effects were found on parent ’s report of children ’s time spent on sedentary behavior and playing outside , parental monitoring food intake , and responsibility regarding nutrition . Conclusion Although the Lifestyle Triple P intervention showed positive effects on some parent reported child behaviors and parenting measures , no effects were visible on children ’s body composition or objective ly measured physical activity . Several adjustments of the intervention content are recommended , for example including a booster session . Trial Registration Nederl and s Trial Register NTR OBJECTIVE To assess the effectiveness of a school and family based healthy lifestyle programme ( WAVES intervention ) compared with usual practice , in preventing childhood obesity . DESIGN Cluster r and omised controlled trial . SETTING UK primary schools from the West Midl and s. PARTICIPANTS 200 schools were r and omly selected from all state run primary schools within 35 miles of the study centre ( n=980 ) , oversampling those with high minority ethnic population s. These schools were r and omly ordered and sequentially invited to participate . 144 eligible schools were approached to achieve the target recruitment of 54 schools . After baseline measurements 1467 year 1 pupils aged 5 and 6 years ( control : 28 schools , 778 pupils ) were r and omised , using a blocked balancing algorithm . 53 schools remained in the trial and data on 1287 ( 87.7 % ) and 1169 ( 79.7 % ) pupils were available at first followup ( 15 month ) and second follow-up ( 30 month ) , respectively . INTERVENTIONS The 12 month intervention encouraged healthy eating and physical activity , including a daily additional 30 minute school time physical activity opportunity , a six week interactive skill based programme in conjunction with Aston Villa football club , signposting of local family physical activity opportunities through mailouts every six months , and termly school led family workshops on healthy cooking skills . OUTCOME MEASURES The protocol defined primary outcomes , assessed blind to allocation , were between arm difference in body mass index ( BMI ) z score at 15 and 30 months . Secondary outcomes were further anthropometric , dietary , physical activity , and psychological measurements , and difference in BMI z score at 39 months in a subset . RESULTS Data for primary outcome analyses were : baseline , 54 schools : 1392 pupils ( 732 controls ) ; first follow-up ( 15 months post-baseline ) , 53 schools : 1249 pupils ( 675 controls ) ; second follow-up ( 30 months postbaseline ) , 53 schools : 1145 pupils ( 621 controls ) . The mean BMI z score was non-significantly lower in the intervention arm compared with the control arm at 15 months ( mean difference −0.075 ( 95 % confidence interval −0.183 to 0.033 , P=0.18 ) in the baseline adjusted models . At 30 months the mean difference was −0.027 ( −0.137 to 0.083 , P=0.63 ) . There was no statistically significant difference between groups for other anthropometric , dietary , physical activity , or psychological measurements ( including assessment of harm ) . CONCLUSIONS The primary analyses suggest that this experiential focused intervention had no statistically significant effect on BMI z score or on preventing childhood obesity . Schools are unlikely to impact on the childhood obesity epidemic by incorporating such interventions without wider support across multiple sectors and environments . TRIAL REGISTRATION Current Controlled Trials IS RCT N97000586 . Introduction Excess weight in childhood is a global problem , affecting around 41 million children under the age of 5 years . In addition to physical and psychosocial health consequences in these early years , childhood For numbered affiliations see end of article . Correspondence to : P Adab [email protected] Cite this as : BMJ 2018;360:k211 http://dx.doi.org/10.1136/bmj.k211 Accepted : 19 December 2017 WhAT IS AlReAdy knoWn on ThIS TopIC Comprehensive systematic review s have suggested that school based interventions could be effective in preventing childhood obesity in high income countries Heterogeneity in intervention components and outcomes limit practical recommendations Furthermore , inconsistent findings in relation to differential effects on subgroups , and impact on inequalities , limited data on potential harms , process measures , and long term effects , as well as lack of data on cost effectiveness , restrict interpretation and wider applicability WhAT ThIS STudy AddS The WAVES study evaluated a theoretically informed , skills based intervention targeting children ’s diet and physical activity behaviours through schools and families It did not result in any meaningful effect on adiposity , dietary intake , or physical activity after 15 or 30 months Although such interventions can fulfil the responsibility of schools for wider education , without upstream support they are unlikely to halt the childhood obesity OBJECTIVE To determine the feasibility , acceptability , and reported impact of a nutrition and physical activity environmental intervention in child care . DESIGN Self- assessment instrument completed pre- and post-intervention by r and omly assigned intervention and comparison child care centers . SETTING Child care centers in 8 counties across North Carolina . PARTICIPANTS A convenience sample of 19 child care centers ( 15 intervention and 4 comparison ) . INTERVENTION Intervention centers completed the self- assessment instrument at baseline and then selected 3 environmental improvements to make over the 6-month intervention period with assistance from a trained NAP SACC Consultant . MAIN OUTCOME MEASURE Changes in pre- and post-intervention self-assesment of the nutrition and physical activity child care environment with additional process measures to evaluate project implementation , feasibility and acceptability . ANALYSIS Comparison of pre- and post-test scores for the intervention group using a Wilcoxon signed-rank test and descriptions of environmental changes . RESULTS Intervention centers rated themselves higher at follow-up than at baseline , and relative to comparison centers , reported a variety of environmental nutrition and physical activity improvements confirmed by research staff . CONCLUSIONS AND IMPLICATION S The NAP SACC pilot intervention shows promise as an approach to promote healthy weight environments in preschool setting s. Additional evaluation of the project is needed using a greater number of centers and a more objective outcome measure Objective : To evaluate the feasibility and efficacy of the ‘ Healthy Dads , Healthy Kids ’ ( HDHK ) program , which was design ed to help overweight fathers lose weight and be a role model of positive health behaviors for their children . Design : R and omized controlled trial . Participants : A total of 53 overweight/obese men ( mean ( s.d . ) age=40.6 ( 7.1 ) years ; body mass index ( BMI ) = 33.2 ( 3.9 ) ) and their primary school-aged children ( n=71 , 54 % boys ; mean ( s.d . ) age=8.2 ( 2.0 ) years ) were r and omly assigned ( family unit ) to either ( i ) the HDHK program ( n=27 fathers , n=39 children ) or ( ii ) a wait-list control group ( n=26 fathers , n=32 children).Intervention : Fathers in the 3-month program attended eight face-to-face education sessions . Children attended three of these sessions . Outcomes : The primary outcome was fathers ’ weight . Fathers and their children were assessed at baseline , and at 3- and 6-month follow-up , for weight , waist circumference , BMI , blood pressure , resting heart rate ( RHR ) , objective ly measured physical activity and self-reported dietary intake . Results : Intention-to-treat analysis revealed significant between-group differences at 6 months for weight loss ( P<0.001 ) , with HDHK fathers losing more weight ( −7.6 kg ; 95 % confidence interval ( CI ) −9.2 , −6.0 ; d=0.54 ) than control group fathers ( 0.0 kg ; 95 % CI −1.4 , 1.6 ) . Significant treatment effects ( P<0.05 ) were also found for waist circumference ( d=0.62 ) , BMI ( d=0.53 ) , systolic blood pressure ( d=0.92 ) , RHR ( d=0.66 ) and physical activity ( d=0.91 ) , but not for dietary intake . In children , significant treatment effects ( P<0.05 ) were found for physical activity ( d=0.74 ) , RHR ( d=0.51 ) and dietary intake ( d=0.84 ) . Conclusion : The HDHK program result ed in significant weight loss and improved health-related outcomes in fathers and improved eating and physical activity among children . Targeting fathers is a novel and efficacious approach to improving health behavior in their children OBJECTIVE This study reports the results of the " Active by Choice Today " ( ACT ) trial for increasing moderate-to-vigorous physical activity ( MVPA ) in low-income and minority adolescents . DESIGN The ACT program was a r and omized controlled school-based trial testing the efficacy of a motivational plus behavioral skills intervention on increasing MVPA in underserved adolescents . Twenty-four middle schools were matched on school size , percentage minorities , percentage free or reduce lunch , and urban or rural setting before r and omization . A total of 1,563 6th grade students ( mean age , 11.3 years , 73 % African American , 71 % free or reduced lunch , 55 % female ) participated in either a 17-week ( over one academic year ) intervention or comparison after-school program . MAIN OUTCOME MEASURE The primary outcome measure was MVPA based on 7-day accelerometry estimates at 2-weeks postintervention and an intermediate outcome was MVPA at midintervention . RESULTS At midintervention students in the intervention condition engaged in 4.87 greater minutes of MVPA per day ( 95 % CI : 1.18 to 8.57 ) than control students . Students in intervention schools engaged in 9.11 min ( 95 % CI : 5.73 to 12.48 ) more of MVPA per day than those in control schools during the program time periods ; indicating a 27 min per week increase in MVPA . No significant effect of the ACT intervention was found outside of school times or for MVPA at 2-weeks postintervention . CONCLUSIONS Motivational and behavioral skills programs are effective at increasing MVPA in low-income and minority adolescents during program hours , but further research is needed to address home barriers to youth MVPA PURPOSE The objective of this study was to evaluate the impact of a school-based intervention ( Program X ) incorporating pedometers and e-mail support on physical activity , sedentary behavior , and healthy eating in adolescents . METHODS A r and omized control trial was used to evaluate the impact of the Program X intervention . Six schools ( N = 124 participants ; mean age 14.1 + /- .8 years ) were r and omized to intervention or control conditions for the 6-month study period . Objective ly recorded physical activity ( mean steps/day ) , self-reported sedentary behavior , and dietary habits were measured at baseline and at 6-month follow-up and intervention effects were assessed using repeated- measures analysis of variance and chi(2 ) tests . RESULTS Participants in the intervention group increased their step counts by 956 + /- 4107 steps/day ( boys ) and 999 + /- 1999 ( girls ) . Repeated- measures analysis of variance revealed significant group-by-time interactions for boys ( F = 7.4 , p = .01 , d = .80 ) and girls ( F = 29.6 , p < .001 , d = 1.27 ) for mean steps/day . The intervention significantly decreased the number of energy-dense/low-nutrient snacks consumed by boys ( chi(2 ) = 4.0 , p = .043 ) and increased the number of fruit serves among girls ( chi(2 ) = 4.8 , p = .028 ) . The intervention did not have a statistically significant effect on sedentary behavior . CONCLUSION A school-based intervention incorporating physical activity monitoring using pedometers and e-mail support was successful in promoting physical activity and selected healthy eating behaviors in adolescent boys and girls 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 BACKGROUND Consumption of sugar-sweetened beverages may cause excessive weight gain . We aim ed to assess the effect on weight gain of an intervention that included the provision of noncaloric beverages at home for overweight and obese adolescents . METHODS We r and omly assigned 224 overweight and obese adolescents who regularly consumed sugar-sweetened beverages to experimental and control groups . The experimental group received a 1-year intervention design ed to decrease consumption of sugar-sweetened beverages , with follow-up for an additional year without intervention . We hypothesized that the experimental group would gain weight at a slower rate than the control group . RESULTS Retention rates were 97 % at 1 year and 93 % at 2 years . Reported consumption of sugar-sweetened beverages was similar at baseline in the experimental and control groups ( 1.7 servings per day ) , declined to nearly 0 in the experimental group at 1 year , and remained lower in the experimental group than in the control group at 2 years . The primary outcome , the change in mean body-mass index ( BMI , the weight in kilograms divided by the square of the height in meters ) at 2 years , did not differ significantly between the two groups ( change in experimental group minus change in control group , -0.3 ; P=0.46 ) . At 1 year , however , there were significant between-group differences for changes in BMI ( -0.57 , P=0.045 ) and weight ( -1.9 kg , P=0.04 ) . We found evidence of effect modification according to ethnic group at 1 year ( P=0.04 ) and 2 years ( P=0.01 ) . In a prespecified analysis according to ethnic group , among Hispanic participants ( 27 in the experimental group and 19 in the control group ) , there was a significant between-group difference in the change in BMI at 1 year ( -1.79 , P=0.007 ) and 2 years ( -2.35 , P=0.01 ) , but not among non-Hispanic participants ( P>0.35 at years 1 and 2 ) . The change in body fat as a percentage of total weight did not differ significantly between groups at 2 years ( -0.5 % , P=0.40 ) . There were no adverse events related to study participation . CONCLUSIONS Among overweight and obese adolescents , the increase in BMI was smaller in the experimental group than in the control group after a 1-year intervention design ed to reduce consumption of sugar-sweetened beverages , but not at the 2-year follow-up ( the prespecified primary outcome ) . ( Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others ; Clinical Trials.gov number , NCT00381160 . ) OBJECTIVE To evaluate the impact of a 12-month multicomponent school-based obesity prevention program , Nutrition and Enjoyable Activity for Teen Girls among adolescent girls . DESIGN Group r and omized controlled trial with 12-month follow-up . SETTING Twelve secondary schools in low-income communities in the Hunter and Central Coast regions of New South Wales , Australia . PARTICIPANTS Three hundred fifty-seven adolescent girls aged 12 to 14 years . INTERVENTION A multicomponent school-based intervention program tailored for adolescent girls . The intervention was based on social cognitive theory and included teacher professional development , enhanced school sport sessions , interactive seminars , nutrition workshops , lunch-time physical activity sessions , h and books and pedometers for self-monitoring , parent newsletters , and text messaging for social support . MAIN OUTCOME MEASURES Body mass index ( BMI , calculated as weight in kilograms divided by height in meters squared ) , BMI z score , body fat percentage , physical activity , screen time , dietary intake , and self-esteem . RESULTS After 12 months , changes in BMI ( adjusted mean difference , -0.19 ; 95 % CI , -0.70 to 0.33 ) , BMI z score ( mean , -0.08 ; 95 % CI , -0.20 to 0.04 ) , and body fat percentage ( mean , -1.09 ; 95 % CI , -2.88 to 0.70 ) were in favor of the intervention , but they were not statistically different from those in the control group . Changes in screen time were statistically significant ( mean , -30.67 min/d ; 95 % CI , -62.43 to -1.06 ) , but there were no group by time effects for physical activity , dietary behavior , or self-esteem . CONCLUSIONS A school-based intervention tailored for adolescent girls from schools located in low-income communities did not significantly reduce BMI gain . However , changes in body composition were of a magnitude similar to previous studies and may be associated with clinical ly important health outcomes . TRIAL REGISTRATION anzctr.org.au Identifier : 12610000330044 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 Type 2 diabetes is increasing among youth , with minority youth at highest risk . This preliminary study tested the feasibility of a school-based program to prevent type 2 diabetes in youth at risk . Forty-one participants ( age 12.6 + /- 1.1 years ; 63 % female , 51 % African American , 44 % Hispanic , and 5 % Caucasian ) were r and omly assigned to one of two groups . Both the experimental and control groups received nutrition education and exercise training . The experimental group also received coping skills training . Data collected included body mass index ( BMI ) , insulin resistance , dietary intake ( 24-Hour Food Recall ) , self-efficacy ( Health Behavior Question naire ) , activity ( Revised Godin-Shepard Activity Survey ) , and parents ' health promoting behaviors ( Health Promoting Lifestyle Profile III ) . At baseline BMI ranged from 27 to 53 ( M = 36.2 + /- 6.0 ) , and 95 % ( n = 39 ) demonstrated insulin resistance or pre-diabetes on an oral glucose tolerance test . After 12 months , the experimental group showed trends in improved usual food choices ( p = .1 ) and increased dietary knowledge ( p = .3 ) . They also demonstrated lower glucose ( p = .07 ) and insulin levels ( p = .2 ) . Experimental group parents demonstrated improved health responsibility ( p = .03 ) , healthier nutrition choices ( p = .05 ) , improved stress management skills ( p = .05 ) , increased activity ( p = .2 ) , and increased spirituality ( p = .2 ) . Data suggest a school-based program tailored to multiethnic youth may prove successful in helping these youth increase activity , improve nutrition status , and stabilize glucose and insulin metabolism , and also may be effective in changing parent health behavior CONTEXT Previous studies indicate that the interpretation of trial results can be distorted by authors of published reports . OBJECTIVE To identify the nature and frequency of distorted presentation or " spin " ( ie , specific reporting strategies , whatever their motive , to highlight that the experimental treatment is beneficial , despite a statistically nonsignificant difference for the primary outcome , or to distract the reader from statistically nonsignificant results ) in published reports of r and omized controlled trials ( RCTs ) with statistically nonsignificant results for primary outcomes . DATA SOURCES March 2007 search of MEDLINE via PubMed using the Cochrane Highly Sensitive Search Strategy to identify reports of RCTs published in December 2006 . STUDY SELECTION Articles were included if they were parallel-group RCTs with a clearly identified primary outcome showing statistically nonsignificant results ( ie , P > or = .05 ) . DATA EXTRACTION Two readers appraised each selected article using a pretested , st and ardized data abstract ion form developed in a pilot test . RESULTS From the 616 published reports of RCTs examined , 72 were eligible and appraised . The title was reported with spin in 13 articles ( 18.0 % ; 95 % confidence interval [ CI ] , 10.0%-28.9 % ) . Spin was identified in the Results and Conclusions sections of the abstract s of 27 ( 37.5 % ; 95 % CI , 26.4%-49.7 % ) and 42 ( 58.3 % ; 95 % CI , 46.1%-69.8 % ) reports , respectively , with the conclusions of 17 ( 23.6 % ; 95 % CI , 14.4%-35.1 % ) focusing only on treatment effectiveness . Spin was identified in the main-text Results , Discussion , and Conclusions sections of 21 ( 29.2 % ; 95 % CI , 19.0%-41.1 % ) , 31 ( 43.1 % ; 95 % CI , 31.4%-55.3 % ) , and 36 ( 50.0 % ; 95 % CI , 38.0%-62.0 % ) reports , respectively . More than 40 % of the reports had spin in at least 2 of these sections in the main text . CONCLUSION In this representative sample of RCTs published in 2006 with statistically nonsignificant primary outcomes , the reporting and interpretation of findings was frequently inconsistent with the results OBJECTIVES This study evaluated the feasibility of the ' Encouraging Activity to Stimulate Young ( EASY ) Minds ' programme , a school-based intervention for integrating physical activity ( PA ) into mathematics lessons . DESIGN R and omised controlled trial . METHODS Two classes from a single school ( n = 54 ) were r and omised to receive either the 6-week EASY Minds intervention ( n = 27 ) or follow their usual school programme ( n = 27 ) . The intervention involved the embedding of PA across the pre-existing mathematics programme for 3 × 60 min sessions per week . Changes in PA were measured using accelerometers and ' on task ' behaviour was measured using momentary time sampling observation . RESULTS Using intention-to-treat analysis , significant intervention effects were found for MVPA ( 9.7 % , 95%CI = 7.6 , 11.8 , p ≤ 0.001 ) and sedentary time ( -22.4 % , CI = -24.9 , -12.2 , p ≤ 0.001 ) for the intervention group during Mathematics lessons ( 9.30 am-10.30 am ) . Significant intervention effects were also shown for MVPA 8.7 % ( 95 % CI = 5.8 , 11.6 , p ≤ 0.001 and sedentary time -18.6 % ( 95 % CI = -24.9 , -12.2 , p ≤ 0.001 ) across the whole school day . Furthermore , children displayed significantly greater ' on-task ' behaviour across the intervention period with a 19.9 % ( 95%CI = 2.4 , 37.4 , p ≤ 0.03 ) mean difference between groups . CONCLUSIONS The EASY Minds programme demonstrated that integrating movement across the primary mathematics syllabus is feasible and efficacious in enhancing school based-PA and improving on-task behaviour in mathematics lessons PURPOSE The purpose of this study was to evaluate the Hunter Illawarra Kids Challenge Using Parent Support physical activity program in overweight children . METHODS A multisite r and omized controlled trial was conducted with three intervention arms : 1 ) child-centered physical activity skill development program ( Activity ) , 2 ) parent-centered dietary modification program ( DIET ) , or 3 ) both programs combined ( PA+DIET ) . Movement skill proficiency , perceived athletic competence , accelerometer-assessed physical activity , and parent-reported time spent in screen behaviors were assessed at baseline , 6 months , and 12 months in 165 prepubertal children aged 5.5 - 9 yr ( 59 % girls , 78 % obese ) . Differences in changes in outcomes between groups were assessed using linear mixed models . RESULTS Compared with the diet group , the activity group ( mean ( 95 % confidence interval ) : + 7.7 units ( 3.8 - 11.6 units ) ) and the activity + diet group ( + 6.7 units ( 2.9 - 10.5 units ) ) displayed 11%-13 % greater improvement in overall movement skill proficiency ( gross motor quotient ) at 6 months . Perceived athletic competence increased across groups at follow-up ( across groups : 6 months = + 0.21 units ( 0.11 - 0.31 units ) , 12 months = + 0.21 units ( 0.07 - 0.35 units ) ) . Groups did not differ statistically for change in physical activity outcomes . Total screen time ( min·wk(-1 ) ) decreased in all groups at 6 months ( across groups : -385.4 ( -501.0 to -269.8 ) ) and in the activity group ( -261.8 ( -470.5 to -53.1 ) ) and activity + diet group ( -340.5 ( -534.6 to -146.4 ) ) at 12 months . The diet group reported greater reductions in TV or DVD viewing time at 6 months compared with the activity group ( 248.6 ( 24.0 - 473.3 ) ) . CONCLUSIONS The activity and the activity + diet programs were efficacious in improving overweight children 's movement skill proficiency . All programs were efficacious in reducing time spent in screen behaviors . Other correlates may need to be targeted in addition to movement skills to increase physical activity among overweight children BACKGROUND Physical inactivity is a risk behavior for cardiovascular and other diseases . Schools can promote public health objectives by increasing physical activity among youth . METHODS The Child and Adolescent Trial for Cardiovascular Health ( CATCH ) was a multicenter , r and omized trial to test the effectiveness of a cardiovascular health promotion program in 96 public schools in four states . A major component of CATCH was an innovative , health-related physical education ( P+ ) program . For 2.5 years , r and omly assigned schools received a st and ardized PE intervention , including curriculum , staff development , and follow-up . RESULTS Systematic analysis of 2,096 PE lessons indicated students engaged in more moderate-to-vigorous physical activity ( MVPA ) in intervention than in control schools ( P = 0.002 ) . MVPA during lessons in intervention schools increased from 37.4 % at baseline to 51.9 % , thereby meeting the established Year 2000 objective of 50 % . Intervention children reported 12 more min of daily vigorous physical activity ( P = 0.003 ) and ran 18.6 yards more than control children on a 9-min run test of fitness ( P = 0.21 ) . CONCLUSIONS The implementation of a st and ardized curriculum and staff development program increased children 's MVPA in existing school PE classes in four geographic and ethnically diverse communities . CATCH PE provides a tested model for improving physical education in American schools Pilot studies represent a fundamental phase of the research process . The purpose of conducting a pilot study is to examine the feasibility of an approach that is intended to be used in a larger scale study . The roles and limitations of pilot studies are described here using a clinical trial as an example . A pilot study can be used to evaluate the feasibility of recruitment , r and omization , retention , assessment procedures , new methods , and implementation of the novel intervention . A pilot study is not a hypothesis testing study . Safety , efficacy and effectiveness are not evaluated in a pilot . Contrary to tradition , a pilot study does not provide a meaningful effect size estimate for planning subsequent studies due to the imprecision inherent in data from small sample s. Feasibility results do not necessarily generalize beyond the inclusion and exclusion criteria of the pilot design . A pilot study is a requisite initial step in exploring a novel intervention or an innovative application of an intervention . Pilot results can inform feasibility and identify modifications needed in the design of a larger , ensuing hypothesis testing study . Investigators should be forthright in stating these objectives of a pilot study . Grant review ers and other stakeholders should expect no more Translational or implementation research that assesses the effectiveness of strategies to promote health behaviours among children that have been previously tested under ' ideal ' conditions is rarely reported . Switch-2-Activity aim ed to examine the effectiveness of an abbreviated programme delivered by teachers targeting children 's television viewing , computer use , physical activity and potential mediators of behaviour change . Fifteen schools from disadvantaged areas in Melbourne , Australia agreed to participate in the study ( 43 % school-level response rate ) . Out of the 1566 Grade s 5 and 6 ( 9 - 12 year old ) children invited to take part in the study , 1048 ( 67 % response rate ) provided informed consent . Schools were r and omized to either an intervention or wait-list control condition . Teachers delivered six lessons , which included strategies such as self-monitoring , behavioural contracting and budgeting of screen time . Children completed a self-report survey at baseline and post-intervention examining screen-based behaviours , physical activity , self-efficacy and behavioural capability . Teachers reported implementation of and attitudes to the programme . Seventy-one per cent of teachers delivered at least four of the six lessons . Most teachers reported that the material s were easy to follow and deliver ; however , many teachers reported modifying the material s in some way . Among boys , there were favourable small intervention effects on weekend screen time [ ( coefficient = -0.62 , 95 % 95 % confidence interval : -1.15 , -0.10 , p = 0.020 ) ] . The intervention also had significant positive effects on children 's self-efficacy for reducing television viewing and on behavioural capability ( television viewing styles ) . Future studies that assess the translation of efficacious programmes and that test whether such programmes are equally effective in different setting s ( e.g. in the family setting ) are urgently required OBJECTIVES To assess the effect of a US obesity prevention intervention on dietary outcomes in English 9 - 10 year old children in 2006 . METHODS A pilot cluster r and omised controlled trial in 19 schools with children aged 9 to 10 with lessons taught by teachers . Diet was assessed at baseline and 5 months later using question naires . Full intention-to-treat analysis ( n=506 ) and analyses using only those with complete baseline and follow-up data ( n=393 ) . RESULTS 8.5 % of children ate 5 or more portions of fruit and vegetables per day . The odds of eating healthy amounts of fruit and vegetables ( OR 1.39 ( 95%CI : 0.69 , 2.80 ) ) and snacks ( OR 1.22 ( 95%CI : 0.68 , 2.21 ) ) were greater in children from the intervention compared to control schools . Point estimates were less than one for consumption of no portions of high fat food and one or zero high energy drinks . A full-scale trial would require 2640 children ( 106 schools ) with 80 % power to detect an odds ratio of at least 1.30 for healthy levels of consumption for the four dietary outcomes , with an alpha level of 0.01 . CONCLUSIONS The US intervention can be transferred to Engl and and it might be effective in increasing fruit and vegetable consumption and decreasing snacks IMPORTANCE Identifying community-based programs that increase physical activity among diverse youth could yield sustainable tools to reduce obesity and obesity disparities . OBJECTIVE To evaluate the impact of a community-based after-school soccer and youth development program , America SCORES , on students ' physical activity , weight status , and fitness . DESIGN Cluster-r and omized trial . Study measures were collected in the fall ( baseline ) , winter ( midpoint ) , and spring ( end point ) of the 2009 - 2010 school year . SETTING After-school programs in 6 schools within a large urban school district . PARTICIPANTS All 4th and 5th grade students in after-school programs at the study schools were eligible . INTERVENTION Three schools were r and omized to receive the SCORES after-school program , delivered via the train-the-trainer model . MAIN OUTCOME MEASURES Change in minutes of after-school moderate-to-vigorous physical activity ( MVPA ) , fitness ( maximal oxygen consumption ) , and body mass index over 1 school year . RESULTS Participants ( n = 156 ) were diverse ( 42 % Latino , 32 % Asian , and 12 % African American ) and 76 ( 49 % ) had a body mass index at or above the 85th percentile . There were no significant group differences in the change in physical activity , fitness , or weight status among all students . However , among students with a body mass index at or above the 85th percentile , SCORES significantly increased MVPA after school ( 3.4 min/d ; 95 % CI , 0.3 - 6.5 ) and on Saturdays ( 18.5 minutes ; 95 % CI , 3.4 - 33.6 ) . CONCLUSIONS AND RELEVANCE Existing community-based programs such as SCORES can increase physical activity among low-income youth , particularly those most at risk for weight-related comorbidities . While evaluating existing programs presents special challenges , partnerships between communities , schools , and research ers are an important component of translational research to address obesity . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01156103 BACKGROUND Most adolescents do not meet national recommendations for nutrition and physical activity . However , no studies of physical activity and nutrition interventions for adolescents conducted in health care setting s have been published . The present study was an initial evaluation of the PACE+ ( Patient-centered Assessment and Counseling for Exercise plus Nutrition ) program , delivered in primary care setting s. PARTICIPANTS Adolescents aged 11 to 18 years ( N = 117 ) were recruited from 4 pediatric and adolescent medicine outpatient clinics . Participants ' mean ( SD ) age was 14.1 ( 2.0 ) years , 37 % were girls , and 43 % were ethnic minorities . INTERVENTION Behavioral targets were moderate physical activity , vigorous physical activity , fat intake , and fruit and vegetable intake . All patients completed a computerized assessment , created tailored action plans to change behavior , and discussed the plans with their health care provider . Patients were then r and omly assigned to receive no further contact or 1 of 3 extended interventions : mail only , infrequent telephone and mail , or frequent telephone and mail . MEASURES Brief , vali date d , self-report measures of target behaviors were collected at baseline and 4 months later . RESULTS All outcomes except vigorous physical activity improved over time , but adolescents who received the extended interventions did not have better 4-month outcomes than those who received only the computer and provider counseling components . Adolescents who targeted a behavior tended to improve more than those who did not target the behavior , except for those who targeted vigorous physical activity . CONCLUSIONS A primary care-based interactive health communication intervention to improve physical activity and dietary behaviors among adolescents is feasible . Controlled experimental research is needed to determine whether this intervention is efficacious in changing behaviors in the short- and long-term The purpose of this study was to determine the feasibility , acceptability , and potential efficacy of a school-based physical activity program delivered during school sport time among adolescent girls from low income predominately linguistically diverse background s in New South Wales , Australia . Using a 3-month , 2-arm , parallel-group pilot RCT design , 38 adolescent girls ( Year 11 ) were recruited to participate in the program and r and omised into intervention ( n=17 ) or control groups ( n=21 ) . The intervention program aim ed to increase physical activity by improving enjoyment , physical self-perception and perceived competence . Baseline and follow-up ( 12 weeks ) assessment s included enjoyment of physical activity , physical self-perception , and objective ly measured physical activity during school sport sessions . Process data were collected through observations of lessons , attendance records , and interviews with participants and staff . Recruitment ( 63 % ) and retention ( 68 % ) goals were less than anticipated but similar to other studies . Participation was higher for the intervention ( 72 % ) than the control ( 60 % ) group and the intervention group reported high levels of satisfaction with the program . At follow-up , girls in the intervention group , compared with the control group , showed greater improvement in their enjoyment of physical activity during school sport ( adjusted mean difference=3.8 , 95 % Confidence Interval [ CI ] -2.4 , 10.1 ; Cohen 's d=0.42 st and ard deviation units ) and body image ( adjusted difference mean=1.0 , 95 % CI -0.4 , 2.3 ; d=0.50 ) . There was a smaller decline in participation in physical activity during school sport ( adjusted mean=13.6 , 95 % CI -21.8 , 48.9 ; d=0.24 ) . This study highlights major barriers confronting adolescent girls ' participation in school sport . Some of these include teacher attitudes and support , activities and programming , purpose and distinction , and student input . Negotiating these barriers and overcoming them in a school setting appears feasible with support from the entire school community OBJECTIVE To evaluate the impact of a multi-component school-based physical activity intervention ( Fit-4-Fun ) on health-related fitness and objective ly measured physical activity in primary school children . METHODS Four Hunter primary schools were recruited in April , 2011 and r and omized by school into treatment or control conditions . Participants included 213 children ( mean age = 10.72 years ± 0.6 ; 52.2 % female ) with the treatment group ( n = 118 ) completing the 8-week Fit-4-Fun Program . Participants were assessed at baseline and 6-month follow-up , with a 91 % retention rate . Cardio-respiratory fitness ( CRF ) ( 20 m shuttle run ) was the primary outcome , and secondary outcomes included body composition ( BMI , BMI ( Z ) ) , muscular fitness ( 7-stage sit-up test , push-up test , basketball throw test , St and ing Jump ) , flexibility ( sit and reach ) and physical activity ( 7 days pedometry ) . RESULTS After 6-months , significant treatment effects were found for CRF ( adjusted mean difference , 1.14 levels , p < 0.001 ) , body composition ( BMI mean , -0.96 kg/m(2 ) , p < 0.001 and BMI z-score mean -0.47 z-scores , p < 0.001 ) , flexibility ( sit and reach mean , 1.52 cm , p = 0.0013 ) , muscular fitness ( sit-ups ) ( mean 0.62 stages , p = 0.003 ) and physical activity ( mean , 3253 steps/day , p < 0.001 ) . There were no group by time effects for the other muscular fitness measures . CONCLUSIONS A primary school-based intervention focusing on fitness education significantly improved health-related fitness and physical activity levels in children This study aim ed to assess the feasibility of a community-based physical activity motor development program , called SHARK , among overweight and obese children . Thirteen overweight or obese children aged 8 - 12 years were recruited to the 10-week program from the Illawarra region of NSW , Australia . Measures at baseline , post-treatment and 9-month follow-up included BMI , motor development , perceived competence , objective ly measured physical activity and performance of an activity of daily living . At post-treatment and follow-up motor development , perceived athletic competence and perceived global self-worth had significantly increased . Although recorded minutes in moderate-to-vigorous activity significantly declined at post-treatment and follow-up , activity daily counts did not . The results indicate that community-based activity programs design ed to improve the motor development and perceived competence of overweight and obese children are feasible and may have important and sustainable benefits . However , a larger sample size and a comparison group are required to determine whether this approach can impact on activity levels and weight status OBJECTIVE . We design ed and tested a novel health promotion program for elementary schools that was based on peer teaching from older to younger schoolchildren ( “ Healthy Buddies ” ) . SUBJECTS AND METHODS . This prospect i ve pilot study compared the effect of our program ( 2–3 hours/week , 21 weeks ) in 2 Canadian elementary schools ( intervention : n = 232 children , the whole school implementing the program ; control : n = 151 ) . Older students ( 4th through 7th grade ) were given direct instruction from 1 intervention teacher and were paired with younger students ( kindergarten through 3rd grade ) for the whole school year . Students in 4th through 7th grade then acted as teachers for their younger “ buddies . ” All lessons included 3 components of healthy living : nutrition , physical activity , and healthy body image . The students first learned how to be positive buddies and learned the 3 components of a healthy life . Thereafter , they learned how to overcome challenges to living a healthy life . Outcome measures ( intervention and control schools at the beginning and end of the school year ) included vali date d question naires that assessed healthy-living knowledge , behavior and attitude , a 9-minute fitness run , self-competence , body satisfaction , disordered eating symptoms , and anthropometry ( BMI , blood pressure , and heart rate ) . RESULTS . Compared with control students , both older and younger intervention students showed an increase in healthy-living knowledge , behavior , and attitude scores and a smaller increase in systolic blood pressure . BMI and weight increased less in the intervention students in 4th through 7th grade and height more in the intervention students in kindergarten through 3rd grade . CONCLUSIONS . Our student-led curriculum improved knowledge not only in older schoolchildren but also in their younger buddies . It also decreased weight velocity in the older students . Student-led teaching may be an efficient , easy-to-implement way of promoting a healthy lifestyle from kindergarten to 7th grade OBJECTIVES This pilot study evaluated the feasibility ( recruitment , retention , and acceptability ) and preliminary efficacy of a six-week home-based electronic time monitor intervention on New Zeal and children 's television watching in 2008 . METHODS Twenty-nine children aged 9 to 12 years who watched more than 20 h of television per week ( 62 % male , mean age 10.4 years ) were r and omised to either the intervention or the control group . The intervention group received an electronic TV time monitor for 6 weeks and advice to restrict TV watching to 1 h per day or less . The control group was given verbal advice to restrict TV watching . RESULTS Participant retention at 6 weeks was 93 % . Semi-structured interviews with intervention families confirmed moderate acceptability of TV time monitors and several perceived benefits including better awareness of household TV viewing and improved time planning . Drawbacks reported included disruption to parents ' TV watching and increased sibling conflict . Time spent watching television decreased by 4.2 h ( mean change [ SD ] : -254 [ 536 ] min ) per week in the intervention group compared with no change in the control group ( -3 [ 241 ] min ) , but the difference between groups was not statistically significant , p=0.77 . Both groups reported decreases in energy intake from snacks and total screen time and increases in physical activity measured by pedometer and between-group differences were not statistically significant . CONCLUSIONS Electronic TV time monitors are feasible to use for home-based TV watching interventions although acceptability varies between families . Preliminary findings from this pilot suggest that such devices have potential to decrease children 's TV watching but a larger trial is needed to confirm effectiveness . Future research should be family-orientated ; take account of other screen time activities ; and employ TV time monitors as just one of a range of strategies to decrease sedentary behaviour INTRODUCTION The preschool years provide a unique window of opportunity to intervene on obesity-related lifestyle risk factors during the formative years of a child 's life . The purpose of this study was to assess the impact of a preschool-based obesity prevention effectiveness trial at 1-year follow-up . DESIGN RCT . SETTING S/ PARTICIPANTS Primarily African American children ( aged 3 - 5 years , N=618 ) attending Head Start preschool programs administered by Chicago Public Schools . METHODS Eighteen preschools were r and omly assigned in 2007 - 2008 to receive either ( 1 ) a 14-week teacher-delivered intervention focused on healthy lifestyle behaviors or ( 2 ) a 14-week teacher-delivered general health curriculum ( control group ) . MAIN OUTCOME MEASURES The primary outcome , BMI , was measured at baseline , postintervention , and 1-year follow-up . Diet and screen time behaviors were also assessed at these time points . Multilevel mixed effects models were used to test for between-group differences . Data were analyzed in 2014 . RESULTS Significant between-group differences were observed in diet , but not in BMI z-score or screen time at 1-year follow-up . Diet differences favored the intervention arm over controls in overall diet quality ( p=0.02 ) and in subcomponents of diet quality , as measured by the Healthy Eating Index-2005 , and in fruit intake ( servings/day , excludes juice ) ( p=0.02 ) . Diet quality worsened more among controls than the intervention group at 1-year follow-up . CONCLUSIONS The adaptation of Hip-Hop to Health Jr. produced modest benefits in diet quality but did not significantly impact weight gain trajectory . Not unlike other effectiveness trials , this real-world version delivered by Head Start teachers produced fewer benefits than the more rigorous efficacy trial . It is important to underst and and build upon the lessons learned from these types of trials so that we can design , implement , and disseminate successful evidence -based programs more widely and effectively . TRIAL REGISTRATION This study is registered at www . clinical trials.gov NCT00241878 OBJECTIVE Many adolescents do not meet national guidelines for participation in regular moderate or vigorous physical activity ( PA ) ; limitations on sedentary behaviors ; or dietary intake of fruits and vegetables , fiber , or total dietary fat . This study evaluated a health care-based intervention to improve these behaviors . DESIGN R and omized controlled trial . SETTING Primary care with follow-up at home . PARTICIPANTS Eight hundred seventy-eight adolescent girls and boys aged 11 to 15 years . INTERVENTIONS Two experimental conditions : ( 1 ) Primary care , office-based , computer-assisted diet and PA assessment and stage-based goal setting followed by brief health care provider counseling and 12 months of monthly mail and telephone counseling and ( 2 ) a comparison condition addressing sun exposure protection . MAIN OUTCOME MEASURES Minutes per week of moderate plus vigorous PA measured by self-report and accelerometer ; self-report of days per week of PA and sedentary behaviors ; and percentage of energy from fat and servings per day of fruits and vegetables measured by three 24-hour diet recalls . Body mass index ( calculated as weight in kilograms divided by the square of height in meters ) was a secondary outcome . RESULTS Compared with adolescents in the sun protection condition , girls and boys in the diet and PA intervention significantly reduced sedentary behaviors ( intervention vs control change , 4.3 to 3.4 h/d vs 4.2 to 4.4 h/d for girls , respectively [ P = .001 ] ; 4.2 to 3.2 h/d vs 4.2 to 4.3 h/d for boys , respectively [ P = .001 ] ) . Boys reported more active days per week ( intervention vs control change : 4.1 to 4.4 d/wk vs 3.8 to 3.8 d/w , respectively [ P = .01 ] ) , and the number of servings of fruits and vegetables for girls approached significance ( intervention vs control change , 3.5 to 4.2 servings/d vs 3.5 to 3.9 servings/d , respectively [ P = .07 ] ) . No intervention effects were seen with percentage of calories from fat or minutes of PA per week . Percentage of adolescents meeting recommended health guidelines was significantly improved for girls for consumption of saturated fat ( intervention vs control change , 23.4 % to 41.0 % vs 18.5 % to 31 % , respectively [ relative risk , 1.33 ; 95 % confidence interval , 1.01 - 1.68 ] ) and for boys ' participation in d/wk of PA ( intervention vs control change , 45.3 % to 55.4 % vs 41.9 % to 38.0 % , respectively [ relative risk , 1.47 ; 95 % confidence interval , 1.19 - 1.75 ] ) . No between-group differences were seen in body mass index . CONCLUSIONS Improvements in some diet , PA , and sedentary behaviors in adolescents can be enabled through the use of a 1-year , integrated intervention using the computer , health provider counseling , mail , and telephone . The amount of intervention received may contribute to its efficacy BACKGROUND This was a pilot study to determine the impact of the Michigan Model ( MM ) Nutrition Curriculum on nutrition knowledge , efficacy expectations , and eating behaviors in middle school students . METHODS The study was conducted in a large metropolitan setting and approved by the Institutional Review Board . The participants for this study were divided into an intervention group ( n = 407 ) and a control group ( n = 169 ) . An MM instructor trained health teachers in the use of the curriculum , and the teacher subsequently taught the curriculum to students in the intervention group . A valid and reliable question naire was used to determine pre-post differences . It consisted of 3 subscales assessing eating habits , nutrition knowledge , and efficacy expectations toward healthy eating . Subscale scores were analyzed using a 2 groups ( intervention vs control ) x 2 times ( pre vs post ) analysis of variance . RESULTS The intervention group increased their nutrition knowledge at post . There was also a significant main effect for groups in the subscales " Eating Behaviors " and " Efficacy Expectations Regarding Healthy Eating . " Subsequent post hoc analysis revealed that the intervention group was significantly more likely to eat fruits and vegetables and less likely to eat junk food than the control group . Students in the intervention group also felt more confident that they could eat healthy . CONCLUSIONS The results of this pilot study suggest that the MM Nutrition Curriculum delivered by trained professionals result ed in significant positive changes in both nutrition knowledge and behaviors in middle school children . Further research needs to be conducted to determine the long-term impact Objectives : To evaluate the effectiveness of an intervention to prevent excess weight gain , reduce time spent in screen behaviours , promote participation in and enjoyment of physical activity ( PA ) , and improve fundamental movement skills among children . Participants : In 2002 , 311 children ( 78 % response ; 49 % boys ) , average age 10 years 8 months , were recruited from three government schools in low socioeconomic areas of Melbourne , Australia . Design : Group-r and omized controlled trial . Children were r and omized by class to one of the four conditions : a behavioural modification group ( BM ; n=66 ) ; a fundamental movement skills group ( FMS ; n=74 ) ; a combined BM/FMS group ( BM/FMS ; n=93 ) ; and a control ( usual curriculum ) group ( n=62 ) . Data were collected at baseline , post intervention , 6- and 12-month follow-up periods . Results : BMI data were available for 295 children at baseline and 268 at 12-month follow-up . After adjusting for food intake and PA , there was a significant intervention effect from baseline to post intervention on age- and sex-adjusted BMI in the BM/FMS group compared with controls ( −1.88 kg m−2 , P<0.01 ) , which was maintained at 6- and 12-month follow-up periods ( −1.53 kg m−2 , P<0.05 ) . Children in the BM/FMS group were less likely than controls to be overweight/obese between baseline and post intervention ( adjusted odds ratio (AOR)=0.36 , P<0.05 ) ; also maintained at 12-month follow-up ( AOR=0.38 , P<0.05 ) . Compared with controls , FMS group children recorded higher levels and greater enjoyment of PA ; and BM children recorded higher levels of PA and TV viewing across all four time points . Gender moderated the intervention effects for participation in and enjoyment of PA , and fundamental movement skills . Conclusion : This programme represents a promising approach to preventing excess weight gain and promoting participation in and enjoyment of PA . Examination of the mediators of this intervention and further tailoring of the programme to suit both genders is required IMPORTANCE Schools are considered an attractive setting to promote healthy living behaviors in children , but previous school-based interventions aim ed at preventing weight gain in children have yielded mixed results . Novel school-based approaches are needed to modify healthy living behaviors and attenuate weight gain in children . OBJECTIVE To assess the effectiveness of a peer-led healthy living program called Healthy Buddies on weight gain and its determinants when disseminated at the provincial level to elementary school students . DESIGN , SETTING , AND PARTICIPANTS Cluster-r and omized effectiveness trial performed during the 2009 - 2010 school year . Baseline and follow-up measurements were made in October 2009 and May 2010 , respectively . The study was performed in 19 elementary schools in Manitoba , Canada , and included 647 elementary school students aged 6 to 12 years ( 48 % girls ) . INTERVENTION Schools were r and omized to receive regular curriculum or Healthy Buddies lesson plans . Lesson plans were delivered by older ( 9- to 12-year-old ) elementary school students to the younger ( 6- to 8-year-old ) peers and targeted 3 components of health : physical activity , healthy eating , and self-esteem and body image . MAIN OUTCOMES AND MEASURES The primary outcome measures were the change in waist circumference and body mass index z score . Secondary outcomes included physical activity ( steps per day ) , cardiorespiratory fitness , self-efficacy , healthy living knowledge , and self-reported dietary intake . RESULTS At baseline , 36 % of children were overweight or obese and 11 % achieved the recommended 13,500 steps per day . Intention-to-treat analyses showed that waist circumference declined significantly in the intervention group relative to controls : -1.42 cm ( -2.68 to -0.17 ; P = .03 ) . Reductions in waist circumference were particularly significant for children who were younger , overweight or obese , or attending First Nations schools . No difference in body mass index z score was observed between groups . Self-efficacy , healthy living knowledge , and dietary intake significantly improved in younger peers who received the intervention compared with students from control schools . No differences were observed in daily step counts or cardiorespiratory fitness between the groups . CONCLUSIONS AND RELEVANCE The implementation of Healthy Buddies lesson plans delivered by older peers within an elementary school setting is an effective method for attenuating increases in central adiposity and improving knowledge of healthy living behaviors among elementary school students . Improvements were achieved with parallel improvements in diet quality , self-efficacy , and knowledge of healthy living . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01979978 BACKGROUND This study tests the feasibility of an innovative school-based program for obesity prevention among adolescent girls . New Moves was implemented as a multicomponent , girls-only , high-school physical education class . METHODS Six schools were equally r and omized into intervention and control conditions . Data were collected at baseline , postintervention , and 8-month follow-up to assess program impact on physical activity , eating patterns , self-perceptions , and body mass index ( BMI ) among 89 girls in the intervention and 112 girls in the control conditions . Program evaluation also included interviews with school staff , parent surveys , and participant interviews and process evaluation surveys . RESULTS The feasibility of implementing New Moves was high , as indicated by strong satisfaction among participants , parents , and school staff , and by program sustainability . Participants perceived a positive program impact on their physical activity , eating patterns , and self-image . Girls in the intervention significantly progressed in their stage of behavioral change for physical activity from baseline to follow-up . However , for the majority of outcome variables , differences between intervention and control schools at postintervention and follow-up were not statistically significant . CONCLUSIONS New Moves was well received and fills a needed niche within school physical education programs . An exp and ed intervention and evaluation is needed to enhance and assess long-term program effectiveness INTRODUCTION Afterschool programs ( ASPs ) across the US are working towards achieving the st and ard of all children accumulating 30min of moderate-to-vigorous physical activity ( MVPA ) during program time . This study describes the two-year impact of an intervention design ed to assist ASPs meeting the 30min/day MVPA st and ard . METHODS Using a two-year delayed treatment , group r and omized controlled trial , 20 ASPs serving ~1700 children/year ( 6 - 12yrs ) were r and omized to either an immediate ( n=10 , baseline-2013 and 2yrs intervention fall-2013-to-spring-2015 ) or delayed group ( n=10 , baseline 2013 - 2014 and 1yr intervention fall-2014-to-spring-2015 ) . The intervention , Strategies-To-Enhance- Practice ( STEPs ) , focused on programming MVPA in the daily schedule , training of staff and leaders , and ongoing technical support/assistance . Accelerometry-derived proportion of children meeting the 30min/day MVPA st and ard was measured in the spring of each year . Mixed model logistic regressions were used to examine the change in the odds of achieving the MVPA st and ard . Analyses were conducted in 2015 . Data were collected in one southeastern US state . RESULTS Immediate boys ( n=677 ) and delayed girls ( n=658 ) increased the percent achieving 30min MVPA/day from 35.9 % to 47.0 % ( odds ratio [OR]=1.88 , 95 % CI 1.18 - 3.00 ) and 13.1 % to 19.1 % ( OR=1.42 , 95 % CI 1.03 - 1.96 ) . Immediate girls ( n=613 ) and delayed boys ( n=687 ) exhibited a nonsignificant increase from 19.1 % to 21.6 % ( OR=1.20 , 95 % CI 0.84 - 1.72 ) and 29.0 % to 31.3 % ( OR=1.13 , 95%CI 0.80 - 1.58 ) . CONCLUSIONS STEPs can have an impact on children 's MVPA and time spent sedentary , yet was unable to fully achieve the goal of all children accumulating 30minMVPA/day . Additional efforts are need to identify strategies ASPs can use to meet this important public health st and ard INTRODUCTION Although comprehensive school-based physical activity interventions are efficacious when tested under research conditions , they often require adaptation in order for implementation at scale . This paper reports the effectiveness of an adapted efficacious school-based intervention in improving children 's moderate to vigorous physical activity . The impact of strategies to support program implementation was also assessed . DESIGN A cluster RCT of low socioeconomic elementary schools in New South Wales , Australia . SETTING / PARTICIPANTS Consenting schools were r and omized ( 25 intervention , 21 control ) using a computerized r and om number function . Follow-up measures were taken at 6 months post-r and omization ( May-August 2015 ) by blinded research assistants . The multicomponent school-based intervention , based on an efficacious school-based physical activity program ( Supporting Children 's Outcomes using Rewards , Exercise and Skills ) , consisted of four physical activity strategies and seven implementation support strategies . The intervention was adapted for scalability and delivery by a local health service over 6 months . The primary outcome was accelerometer assessed , student mean daily minutes spent in moderate to vigorous physical activity . Physical education lesson quality and other school physical activity practice s were also assessed . RESULTS Participants ( n=1,139 , 49 % male ) were third- through sixth- grade students at follow-up ( May-August 2015 ) . Valid wear time and analysis of data were provided for 989 ( 86 % ) participants ( 571 intervention , 568 control ) . At 6-month follow-up , there were no significant effects in overall daily minutes of moderate to vigorous physical activity between groups ( 1.96 minutes , 95 % CI= -3.49 , 7.41 , p=0.48 ) . However , adjusted difference in mean minutes of overall vigorous physical activity ( 2.19 , 95 % CI=0.06 , 4.32 , p=0.04 ) ; mean minutes of school day moderate to vigorous physical activity ( 2.90 , 95 % CI=0.06 , 5.85 , p=0.05 ) ; and mean minutes of school day vigorous physical activity ( 1.81 , 95 % CI=0.78 , 2.83 , p≤0.01 ) were significantly different in favor of the intervention group . Physical education lesson quality and school physical activity practice s were significantly different favoring the intervention group ( analyzed October 2015-January 2016 ) . CONCLUSIONS The modified intervention was not effective in increasing children 's overall daily minutes of moderate to vigorous physical activity , when adapted for implementation at scale . However , the intervention did improve daily minutes of vigorous physical activity and school day moderate to vigorous physical activity , lesson quality , and school physical activity practice s. TRIAL REGISTRATION Australian New Zeal and Clinical Trials Registry : ACTRN12615000437561 PURPOSE Physical activity ( PA ) declines dramatically during adolescence , and activity levels are consistently lower among children living in low-income communities . Competency in a range of fundamental movement skills ( FMS ) may serve as a protective factor against the decline in PA typically observed during adolescence . The purpose of this study was to evaluate the effect of a 12-month multicomponent PA and FMS intervention on children attending primary schools in low-income communities . METHODS The Supporting Children 's Outcomes using Rewards , Exercise , and Skills intervention was evaluated using a cluster r and omized controlled trial . The sample included 25 classes from eight primary schools located in low-income communities . Participants were 460 children ( 54.1 % girls ) age 8.5 ± 0.6 yr . Primary outcomes were objective ly measured PA ( ActiGraph GT3X and GT3X+ accelerometers ) , FMS competency ( Test of Gross Motor Development 2 , six locomotor and six object control skills ) , and cardiorespiratory fitness ( 20-m multistage fitness test ) assessed at baseline , midprogram ( 6-months ) , and at posttest ( 12 months ) . Linear mixed models , adjusted for sex , age , body mass index z-score , socioeconomic status , ethnicity , and school class as a r and om factor , were used to assess the effect of the intervention . RESULTS At midprogram , there were no significant intervention effects for any of the outcomes . At posttest ( study 's primary time point ) , there were intervention effects for daily moderate-to-vigorous PA ( MVPA ) ( adjusted mean difference , 12.7 min·d of MVPA ; 95 % confidence interval ( CI ) , 5.0 - 20.5 ) , overall FMS competency ( 4.9 units ; 95 % CI , -0.04 to 9.8 ) , and cardiorespiratory fitness ( 5.4 laps ; 95 % CI , 2.3 - 8.6 ) . CONCLUSIONS A school-based multicomponent PA and FMS intervention maintained daily MVPA , improved overall FMS competency , and increased cardiorespiratory fitness among children attending primary schools in low-income communities OBJECTIVES To assess the impact of a culturally proficient dietary/physical activity intervention on changes in body mass index ( BMI ) ( kg/m 2 ) . STUDY DESIGN R and omized controlled trial ( Hip-Hop to Health Jr. ) conducted between September 1999 and June 2002 in 12 Head Start preschool programs in Chicago , Illinois . RESULTS Intervention children had significantly smaller increases in BMI compared with control children at 1-year follow-up , 0.06 vs 0.59 kg/m 2 ; difference -0.53 kg/m 2 ( 95 % CI -0.91 to -0.14 ) , P = .01 ; and at 2-year follow-up , 0.54 vs 1.08 kg/m 2 ; difference -0.54 kg/m 2 ( 95 % CI -0.98 to -0.10 ) , P = .02 , with adjustment for baseline age and BMI . The only significant difference between intervention and control children in food intake/physical activity was the Year 1 difference in percent of calories from saturated fat , 11.6 % vs 12.8 % ( P = .002 ) . CONCLUSIONS Hip-Hop to Health Jr. was effective in reducing subsequent increases in BMI in preschool children . This represents a promising approach to prevention of overweight among minority children in the preschool years Objective : To develop and evaluate “ Families for Health ” , a new community based family intervention for childhood obesity . Design : Programme development , pilot study and evaluation using intention-to-treat analysis . Setting : Coventry , Engl and . Participants : 27 overweight or obese children aged 7–13 years ( 18 girls , 9 boys ) and their parents , from 21 families . Intervention : Families for Health is a 12-week programme with parallel groups for parents and children , addressing parenting , lifestyle change and social and emotional development . Main outcome measures : Change in baseline BMI z score at the end of the programme ( 3 months ) and 9-month follow-up . Attendance , drop-out , parents ’ perception of the programme , child ’s quality of life and self-esteem , parental mental health , parent – child relationships and lifestyle changes were also measured . Results : Attendance rate was 62 % , with 18 of the 27 ( 67 % ) children completing the programme . For the 22 children with follow-up data ( including four who dropped out ) , BMI z score was reduced by −0.18 ( 95 % CI −0.30 to −0.05 ) at 3 months and −0.21 ( −0.35 to −0.07 ) at 9 months . Statistically significant improvements were observed in children ’s quality of life and lifestyle ( reduced sedentary behaviour , increased steps and reduced exposure to unhealthy foods ) , child – parent relationships and parents ’ mental health . Fruit and vegetable consumption , participation in moderate/vigorous exercise and children ’s self-esteem did not change significantly . Topics on parenting skills , activity and food were rated as helpful and used with confidence by most parents . Conclusions : Families for Health is a promising new childhood obesity intervention . Definitive evaluation of its clinical effectiveness by r and omised controlled trial is now required OBJECTIVES Educator-led programs for physical activity and motor skill development show potential but few have been implemented and evaluated using a r and omized controlled design . Furthermore , few educator-led programs have evaluated both gross motor skills and physical activity . Therefore , the aim of this study was to evaluate a gross motor skill and physical activity program for preschool children which was facilitated solely by childcare educators . DESIGN A six-month 2-arm r and omized controlled trial was implemented between April and September 2012 in four early childhood centers in Tasmania , Australia . METHODS Educators participated in ongoing professional development sessions and children participated in structured physical activity lessons and unstructured physical activity sessions . RESULTS In total , 150 children were recruited from four centers which were r and omized to intervention or wait-list control group . Six early childhood educators from the intervention centers were trained to deliver the intervention . Gross motor skills were assessed using the Test of Gross Motor Development ( 2nd edition ) and physical activity was measured objective ly using GT3X+ Actigraph accelerometers . No statistically significant differences were identified . However , small to medium effect sizes , in favor of the intervention group , were evident for four of the five gross motor skills and the total gross motor skill score and small to medium effect sizes were reported for all physical activity outcomes . CONCLUSIONS This study highlights the potential of educator-led physical activity interventions and supports the need for further translational trials within the early childhood sector BACKGROUND Limited intervention success in increasing and sustaining girls ' moderate-to-vigorous physical activity ( MVPA ) underscores a need for continued research . PURPOSE The aim of this study was to evaluate the effect of a 17-week Girls on the Move ( GOTM ) intervention on increasing MVPA among fifth- to eighth- grade girls . METHODS This study is a group ( cluster ) r and omized trial , including 24 schools , pair matched and assigned to intervention ( n = 12 ) or control ( n = 12 ) conditions . Participants included 1,519 girls in racially diverse public schools in urban , underserved areas of the Midwestern USA . The intervention included three components : ( i ) 90-min after-school physical activity ( PA ) club offered 3 days/week ; ( ii ) two motivational , individually tailored counseling sessions ; and ( iii ) an interactive Internet-based session at the midpoint of the intervention . Main outcome measures were weighted mean minutes of MVPA per week post-intervention and at 9-month follow-up measured via accelerometer . RESULTS No between-group differences occurred for weighted mean minutes of MVPA per week at post-intervention ( B = -0.08 , p = .207 ) or 9-month follow-up ( B = -0.09 , p = .118 ) while controlling for baseline MVPA . CONCLUSIONS Research is needed to identify interventions that assist girls in attaining and maintaining adequate PA . CLINICAL TRIALS.GOV IDENTIFIER NCT01503333 Importance Rapid growth and elevated weight status in early childhood increase risk for later obesity , but interventions that improve growth trajectories are lacking . Objective To examine effects of a responsive parenting intervention design ed to promote developmentally appropriate , prompt , and contingent responses to a child ’s needs on weight outcomes at 3 years . Design , Setting , and Participants A single-center r and omized clinical trial comparing a responsive parenting intervention design ed to prevent childhood obesity vs a home safety intervention ( control ) among 279 primiparous mother-child dyads ( responsive parenting group , 140 ; control group , 139 ) who enrolled and completed the first home visit from January 2012 through March 2014 with follow-up to age 3 years ( completed by April 2017 ) . Interventions Research nurses conducted 4 home visits during infancy and annual research center visits . The responsive parenting curriculum focused on feeding , sleep , interactive play , and emotion regulation . The control curriculum focused on safety . Main Outcomes and Measures The primary outcome was body mass index ( BMI ) z score at 3 years ( z score of 0 represents the population mean ; 1 and −1 represent 1 SD above and below the mean , respectively ) . BMI percentile at 3 years was design ated previously as the primary outcome . Secondary outcomes included the prevalence of overweight ( BMI ≥85th percentile and < 95th percentile ) and obesity ( BMI ≥95th percentile ) at 3 years . Results Among 291 mother-child dyads r and omized , 279 received the first home visit and were included in the primary analysis . 232 mother-child dyads ( 83.2 % ) completed the 3-year trial . Mean age of the mothers was 28.7 years ; 86 % were white and 86 % were privately insured . At age 3 years , children in the responsive parenting group had a lower mean BMI z score ( −0.13 in the responsive parenting group vs 0.15 in the control group ; absolute difference , −0.28 [ 95 % CI , −0.53 to −0.01 ] ; P = .04 ) . Mean BMI percentiles did not differ significantly ( 47th in the responsive parenting group vs 54th in the control group ; reduction in mean BMI percentiles of 6.9 percentile points [ 95 % CI , −14.5 to 0.6 ] ; P = .07 ) . Of 116 children in the responsive parenting group , 13 ( 11.2 % ) were overweight vs 23 ( 19.8 % ) of 116 children in the control group ( absolute difference , −8.6 % [ 95 % CI , −17.9 % to 0.0 % ] ; odds ratio [ OR ] , 0.51 [ 95 % CI , 0.25 to 1.06 ] ; P = .07 ) ; 3 children ( 2.6 % ) in the responsive parenting group were obese vs 9 children ( 7.8 % ) in the control group ( absolute difference , −5.2 % [ 95 % CI , −10.8 % to 0.0 % ] ; OR , 0.32 [ 95 % CI , 0.08 to 1.20 ] ; P = .09 ) . Conclusions and Relevance Among primiparous mother-child dyads , a responsive parenting intervention initiated in early infancy compared with a control intervention result ed in a modest reduction in BMI z scores at age 3 years , but no significant difference in BMI percentile . Further research is needed to determine the long-term effect of the intervention and assess its efficacy in other setting s. Trial Registration Clinical Trials.gov Identifier : This systematic review examines the level and prevalence of spin in presenting findings that are not statistically significant in published reports of cardiovascular r and omized clinical trials ( RCTs ) BACKGROUND In 2011 , the U.S. Young Men 's Christian Association ( YMCA ) adopted activity st and ards recommending that afterschool programs ( ASPs ) ensure all children engage in a minimum of 30 minutes of moderate to vigorous physical activity ( MVPA ) daily during the ASP . ASPs decide how to accomplish this st and ard , for which few effective strategies exist . PURPOSE To evaluate strategies design ed to help ASPs meet the MVPA st and ard . DESIGN Single group intervention with pretest and three follow-up measures repeated-cross-sectional design with a sub sample cohort . SETTING / PARTICIPANTS Four large-scale YMCA ASPs , serving approximately 500 children each day . INTERVENTION Community-based participatory development of strategies focused on modification of program schedules , professional development training , and weekly checklists to evaluate activity opportunities . MAIN OUTCOME MEASURES Accelerometry-derived MVPA classified as meet or fail-to-meet the 30 minutes ' MVPA/day st and ard collected over a minimum of 4 nonconsecutive days at baseline ( fall 2011 ) and three follow-up assessment s ( spring 2012 , fall 2012 , spring 2013 ) . R and om intercept logistic regression models evaluated the probability of meeting the st and ard for boys and girls , separately ( analyzed summer 2013 ) . RESULTS A total of 895 children ( aged 5 - 12 years , 48.4 % girls ) representing 3654 daily measures were collected across the four assessment s. The percentage of girls and boys meeting the MVPA st and ard at baseline was 13.3 % and 28.0 % , respectively . By spring 2013 , this increased to 29.3 % and 49.6 % . These changes represented an increase in the odds of meeting the 30 minutes ' MVPA/day st and ard by 1.5 ( 95 % CI=1.1 , 2.0 ) and 2.4 ( 95 % CI=1.2 , 4.8 ) for girls and boys , respectively . CONCLUSIONS The strategies developed herein represent an effective approach to enhancing current practice within YMCA ASPs to achieve existing MVPA st and ards . Additional work is necessary to evaluate the scalability of the strategies in a larger sample of ASPs OBJECTIVE To explore the effects of an innovative school-based intervention for increasing physical activity . METHODS 226 children ( 5 - 7 years old ) r and omly selected from 12 Australian primary schools were recruited to a cluster r and omised trial with schools r and omly allocated to intervention or control conditions . The 13-week intervention comprised : ( 1 ) altering the school playground by introducing loose material s and ( 2 ) a teacher-parent intervention exploring perceptions of risk associated with children 's free play . The primary outcomes were total accelerometer counts and moderate-vigorous physical activity during break times . Testing took place in Sydney , 2009 - 2010 . RESULTS 221 participants were tested at baseline . Mixed-effect multilevel regression revealed a small but significant increase from the intervention on total counts ( 9400 counts , 95 % CI 3.5 - 15.2 , p=0.002 ) and minutes of MVPA ( 1.8 min , 95 % CI 0.5 - 3.1 , p=0.006 ) ; and a decrease in sedentary activity ( 2.1 min , 95 % CI 0.5 - 3.8 , p=0.01 ) during break times . We retested children in one intervention school after 2 years ; they maintained the gains . CONCLUSIONS Capturing children 's intrinsic motivations to play while simultaneously helping adults reconsider views of free play as risky provided increases in physical activity during break times . Using accelerometry as the sole measure of physical activity may underestimate the effect . TRIAL REGISTRATION ACTRN12611000089932 OBJECTIVE To evaluate the effectiveness of the ' Healthy Dads , Healthy Kids ( HDHK ) ' program when delivered by trained facilitators in community setting s. METHOD A two-arm r and omized controlled trial of 93 overweight/obese fathers ( mean [ SD ] age=40.3 [ 5.3 ] years ; BMI = 32.5 [ 3.8 ] kg/m(2 ) ) and their primary school-aged children ( n=132 ) from the Hunter Region , Australia . In 2010 - 2011 , families were r and omized to either : ( i ) HDHK intervention ( n=48 fathers , n=72 children ) or ( ii ) wait-list control group . The 7-week intervention included seven sessions and re sources ( booklets , pedometers ) . Assessment s were held at baseline and 14-weeks with fathers ' weight ( kg ) as the primary outcome . Secondary outcomes for fathers and children included waist , BMI , blood pressure , resting heart rate , physical activity ( pedometry ) , and self-reported dietary intake and sedentary behaviors . RESULTS Linear mixed models ( intention-to-treat ) revealed significant between-group differences for fathers ' weight ( P<.001 , d=0.24 ) , with HDHK fathers losing more weight ( -3.3 kg ; 95%CI , -4.3 , -2.4 ) than control fathers ( 0.1 kg ; 95%CI , -0.9,1.0 ) . Significant treatment effects ( P<.05 ) were also found for fathers ' waist ( d=0.41 ) , BMI ( d=0.26 ) , resting heart rate ( d=0.59 ) , energy intake ( d=0.49 ) and physical activity ( d=0.46 ) and for children 's physical activity ( d=0.50 ) and adiposity ( d=0.07 ) . DISCUSSION HDHK significantly improved health outcomes and behaviors in fathers and children , providing evidence for program effectiveness when delivered in a community setting BACKGROUND To evaluate the impact of a primary school-based physical activity ( PA ) integration program delivered by teachers on objective ly measured PA and key educational outcomes . METHODS Ten classes from 8 Australian public schools were r and omly allocated to treatment conditions . Teachers from the intervention group were taught to embed movement-based learning in their students ' ( n = 142 ) daily mathematics program in 3 lessons per week for 6 weeks . The control group ( n = 98 ) continued its regular mathematics program . The primary outcome was accelerometer-determined PA across the school day . Linear mixed models were used to analyze treatment effects . RESULTS Significant intervention effects were found for PA across the school day ( adjusted mean difference 103 counts per minute [ CPM ] , 95 % confidence interval [ CI ] , 36.5 - 169.7 , P = .008 ) . Intervention effects were also found for PA ( 168 CPM , 95 % CI , 90.1 - 247.4 , P = .008 ) and moderate-to-vigorous PA ( 2.6 % , 95 % CI , 0.9 - 4.4 , P = .009 ) in mathematics lessons , sedentary time across the school day ( -3.5 % , 95 % CI , -7.0 to -0.13 , P = .044 ) and during mathematics ( -8.2 % , CI , -13.0 to -2.0 , P = .010 ) and on-task behavior ( 13.8 % , 95 % CI , 4.0 - 23.6 , P = .011)-but not for mathematics performance or attitude . CONCLUSION Integrating movement across the primary mathematics syllabus is feasible and efficacious |
12,980 | 24,134,531 | The limited number of trials was insufficient to show the superiority of LC over other treatments in lowering vascular calcification or cardiovascular events and in improving bone morphology , bone metabolism , or bone turn-over parameters .
LC decreased the serum phosphorus level and calcium × phosphate product ( Ca × P ) as compared to placebo .
LC , calcium carbonate ( CC ) , and sevelamer hydrochloride ( SH ) were comparable in terms of controlling the serum phosphorus , Ca × P product , and intact parathyroid hormone ( iPTH ) levels .
However , LC result ed in a lower serum calcium level and a higher bone-specific alkaline phosphatase level compared with CC .
LC had higher total cholesterol and low-density lipoprotein ( LDL ) cholesterol levels compared with SH .
LC-treated patients appeared to have a higher rate of vomiting and lower risk of hypercalcemia , diarrhea , intradialytic hypotension , cramps or myalgia , and abdominal pain .
Meta- analysis showed no significant difference in the incidence of other side effects .
Accumulation of LC in blood and bone was below toxic levels .
Conclusions LC has high efficacy in lowering serum phosphorus and iPTH levels without increasing the serum calcium .
Current evidence does not show a higher rate of adverse effects for LC compared with other treatments , except for a higher incidence of vomiting .
Moreover , LC accumulation in blood and bone was below toxic levels . | Background Chronic kidney disease – mineral and bone disorder ( CKD – MBD ) is a common complication in CKD patients , particularly in those with end-stage renal disease that requires dialysis .
Lanthanum carbonate ( LC ) is a potent , non-aluminum , non-calcium phosphate binder .
This systematic review evaluates the efficacy and safety of LC in CKD-MBD treatment for maintenance-dialysis patients . | Introduction : Uremic toxins play a pivotal role in the development of systemic complications of chronic kidney disease ( CKD ) , which are largely mediated by the activation of the immune system . Triggers of inflammation in CKD are largely unknown and strategies aim ing to reduce circulating lig and s that could start the inflammatory response are potentially important . In the present study , we investigated the impact of sevelamer hydrochloride treatment in reducing endotoxemia and inflammation in a group of hemodialysis ( HD ) patients . Material and Methods : HD patients , who were converted from calcium carbonate treatment to sevelamer according to KDOQI guidelines , were included and prospect ively followed for 6 months . Systemic inflammation was evaluated by serum ultra-high-sensitivity C-reactive protein ( hsCRP ) using an automated immunoturbidimetric assay . Endotoxin was measured using Limulus amebocyte lysate chromogenic endpoint assay . All the analyses were performed immediately before conversion and after 6 months of treatment . Results : After the exclusion of patients discontinuing the treatment , 20 patients ( mean dialysis time 12 ± 4 months on HD , age 52 ± 2 years , 38 % males , 11 % diabetics ) were included in the analysis . No significant changes were observed in Ca , P and PTH levels , while a reduction in cholesterol levels was seen . Plasma concentration of hsCRP and endotoxin significantly decreased after 6 months of conversion to sevelamer compared with baseline . Conclusion : We conclude that sevelamer treatment leads to a decrease in hsCRP levels , which was accompanied by a parallel decrease in endotoxemia , suggesting that endotoxemia may contribute to the systemic inflammation in HD patients , which was partially reduced by the use of sevelamer AIMS No conventional phosphate binder is entirely satisfactory for the treatment of hyperphosphatemia in patients with end-stage renal disease ( ESRD ) . Consequently , there is a need for new agents . One such agent is lanthanum carbonate ( La ) . This large-scale study compares the safety of La with st and ard therapy ( any approved phosphate binder ) in patients who were treated for up to 2 years . Efficacy , having previously been demonstrated , was a secondary endpoint . MATERIAL S AND METHODS After washout , patients were r and omized to receive La ( n=682 ) or their pre- study phosphate binder ( n=677 ) . Over a 6-week period , La was titrated to a maximum daily dose of 3000 mg elemental lanthanum ( serum phosphorus target levels for titration were < or = 5.9 mg/dl ( 1.90 mmol/l ) ) . Safety assessment s included adverse events ( AEs ) , full laboratory parameters and blood profiles . Efficacy assessment s included serum phosphorus , calcium , calcium x phosphorus product and parathyroid hormone ( PTH ) levels . RESULTS Average treatment exposure was greater in the st and ard therapy group ( 501.4 days ) than in the La group ( 370.3 days ) because st and ard therapy patients who switched or combined treatments were allowed to continue in the study . The most common AEs were gastrointestinal . The incidences of AEs in the La and treatment exposure-corrected st and ard therapy groups were nausea , 37 versus 29 % ; vomiting , 27 versus 22 % and diarrhea ( 24 % in each group ) . Hypercalcemia that was reported as an AE ( La versus treatment exposure-corrected st and ard therapy ) occurred in 4.3 % and 8.4 % of patients , respectively . There was no indication of liver toxicity , suppression of erythropoiesis or changes in the mini-mental state examination . Over 2 years , phosphorus control was similar in both groups ; in the La group , however , serum calcium was lower and serum PTH levels were maintained in the range recommended by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative ( K/DOQI ) . CONCLUSIONS The 2-year tolerability and efficacy of La are similar to those seen with st and ard therapy , although lower serum calcium levels and improved PTH levels were observed in the La group . These results support La as a viable new option for the management of hyperphosphatemia in ESRD AIMS High serum phosphorus levels are a common problem in patients receiving long-term dialysis treatment . Lanthanum carbonate ( Fosrenol ) is a new non-aluminum , non-calcium phosphate binder developed for the treatment of hyperphosphatemia in patients with end-stage renal disease ( ESRD ) . We report data from a recent trial , which , for the first time , assessed the efficacy and tolerability of lanthanum carbonate treatment , compared with placebo , in Chinese patients with ESRD . PATIENTS AND METHODS Following a one- to three-week washout phase and a four-week , open-label lanthanum carbonate dose-titration phase , male and female hemodialysis patients were r and omized ( 1:1 ) to receive either lanthanum carbonate or placebo for four weeks . The primary efficacy parameter of the study was the control of serum phosphorus levels ( < or = 1.8 mmol/l [ < or = 5.6 mg/dl ] ) . Secondary endpoints included the profile of serum phosphorus during titration and parathyroid hormone , calcium , and calcium x phosphorus ( Ca x P ) product levels . The safety and tolerability of lanthanum carbonate were assessed by monitoring adverse events throughout the study . RESULTS Mean serum phosphorus level at the end of washout was 2.5 + /- 0.5 mmol/l ( 7.7 + /- 1.5 mg/dl ; n=73 ) , and there was no evidence of a difference in levels between the treatment groups pre-r and omization . At the end of the study , lanthanum carbonate-treated patients had significantly lower phosphorus levels ( 1.6 + /- 0.5 mmol/l [ 5.1 + /- 1.5 mg/dl ] ; n=30 ) than those receiving placebo ( 2.3 + /- 0.4 mmol/l [ 7.2 + /- 1.3 mg/dl ] ; n=31 ; p < 0.001 ) . In addition , a significantly higher proportion of patients receiving lanthanum carbonate had controlled serum phosphorus levels ( 60 % ) compared with the placebo group ( 10 % ; p < 0.001 ) . Ca x P product levels were also significantly lower in the lanthanum carbonate group at the end of r and omized treatment ( p < 0.001 ) . Lanthanum carbonate was well tolerated ; only one serious adverse event was reported , which was unrelated to treatment . CONCLUSIONS Lanthanum carbonate was shown to be an effective and well-tolerated phosphate binder for the treatment of hyperphosphatemia in Chinese patients with ESRD . This finding supports the results of previous US and European studies , which have also shown that lanthanum carbonate treatment effectively controls serum phosphorus levels Background : Control of serum phosphate over the long term is essential in patients with end-stage renal disease . Six-month and 2-year extensions to a 6-month study evaluated the long-term safety , tolerability and efficacy of the new phosphate binder lanthanum carbonate . Methods : Patients who participated in a 6-month , r and omized trial comparing lanthanum carbonate with calcium carbonate were eligible for a 24-week , open-label extension . Lanthanum carbonate-treated patients continued taking their established maintenance dose ( ‘ continued-lanthanum group ’ ) and calcium carbonate-treated patients switched to lanthanum carbonate , 375–3,000 mg/day ( ‘ switch group ’ ) . Patients could also enter a further 2-year extension . Efficacy parameters , including serum phosphate , were monitored . Results : Mean serum phosphate was ∼1.80 mmol/l throughout the trial . The percentage of patients with controlled serum phosphate ( ≤1.80 mmol/l ) after the 6-month extension was 63.3 and 58.4 % in the continued-lanthanum and switch groups , respectively ; after the 2-year extension , 54.4 % of patients had controlled serum phosphate . After discontinuation of calcium carbonate and initiation of lanthanum carbonate , the hypercalcemia incidence was 2.7 % , compared with 20.2 % during the double-blind phase . Calcium × phosphate product was maintained at an acceptable level . Lanthanum carbonate was well tolerated ; adverse events were mild/moderate and mainly gastrointestinal . Conclusions : Lanthanum carbonate maintains effectiveness with continued tolerability for up to 3 years Background Serum phosphorus control is critical for chronic kidney disease ( CKD ) 5D patients . Currently , clinical profile for an oral phosphorus binder in the mainl and Chinese population is not available . Objective To establish the efficacy , safety , and tolerability of lanthanum carbonate in CKD 5D patients . Design Multicenter , r and omized , double blind , placebo-controlled study . A central r and omization center used computer generated tables to allocate treatments . Setting Twelve tertiary teaching hospitals and medical university affiliated hospitals in mainl and China . Participants Overall , 258 hemodialysis or continuous ambulatory peritoneal dialysis ( CAPD ) adult patients were enrolled . InterventionAfter a 0–3-week washout period and a 4-week lanthanum carbonate dose-titration period , 230 patients were r and omized 1:1 to receive lanthanum carbonate ( 1500 mg-3000 mg ) or placebo for a further 4-week maintenance phase . Main outcome measures Efficacy and safety of lanthanum carbonate to achieve and maintain target serum phosphorus concentrations were assessed . Results In the titration phase , serum phosphorus concentrations of all patients decreased significantly . About three-fifths achieved target levels without significantly disturbing serum calcium levels . At the end of the maintenance period , the mean difference in serum phosphorus was significantly different between the lanthanum carbonate and placebo-treated groups ( 0.63±0.62 mmol/L vs. 0.15±0.52 mmol/L , P < 0.001 ) . The drug-related adverse effects were mild and mostly gastrointestinal in nature . Conclusion Lanthanum carbonate is an efficacious and well-tolerated oral phosphate binder with a mild AE profile in hemodialysis and CAPD patients . This agent may provide an alternative for the treatment of hyperphosphatemia in CKD 5D patients in mainl and China . Trial registration No. BACKGROUND The majority of patients with end-stage renal disease on dialysis are hyperphosphataemic . Lanthanum carbonate has been shown to be a highly effective phosphate binder in pre- clinical studies . A 4-week , open-label , dose-titration trial was conducted to assess the ability of lanthanum carbonate to control phosphate levels in patients with chronic renal failure . METHODS This preliminary study was of 6 weeks duration : 2 weeks of washout followed by 4 weeks of dose titration . Patients ( n = 59 ) were titrated on the basis of weekly serum phosphate levels from a daily dose of 375 mg lanthanum carbonate to a maximum dose of 2250 mg . Patients were maintained on the dose that controlled serum phosphate to between 1.30 and 1.80 mmol/l ( 4.03 - 5.58 mg/dl ) . Serum phosphate levels represented the main efficacy assessment . Safety was also evaluated . RESULTS Most patients were successfully titrated to 1500 and 2250 mg lanthanum/day ( mean dose at end of titration : 1278 mg ) . At completion of the study 70 % of patients achieved a serum phosphate of < or=1.80 mmol/l . The use of lanthanum carbonate in patients undergoing continuous ambulatory peritoneal dialysis or haemodialysis was generally well tolerated . CONCLUSIONS Lanthanum carbonate , a new non-aluminium , non-calcium phosphate binder , effectively reduces serum phosphate levels . Results of longer-term efficacy and safety studies are awaited with interest BACKGROUND Atherosclerosis and vascular calcification ( VC ) progression in chronic kidney disease is favored by disturbances of mineral metabolism . We compared the effect of phosphate binder lanthanum ( La ) carbonate with sevelamer-HCl on atherosclerosis , VC and bone structure and function in mice with chronic renal failure ( CRF ) . METHODS Apolipoprotein E-deficient ( apoE(-/- ) ) mice were r and omized to one non-CRF and three CRF groups , fed with st and ard diet ( one non-CRF and one CRF ) or diet supplemented with either 3 % lanthanum carbonate ( La3 % ) or 3 % sevelamer-HCl ( Sev3 % ) . RESULTS Both La3 % and Sev3 % supplemented CRF mice displayed a decrease of serum phosphorus , calcification at both intimal and medial aortic sites and atherosclerosis . This was associated with a reduction of plaque Type I collagen expression by both binders and of positive nitrotyrosine staining in response to sevelamer-HCl only . Increased mineral apposition and bone formation rates in unsupplemented CRF mice were reduced by Sev3 % but not by La3 % . CONCLUSIONS The beneficial effects of La carbonate and sevelamer-HCl on the progression of VC and atherosclerosis in CRF mice could be mainly due to a decrease in phosphate retention and likewise a reduction of arterial Type I collagen expression . The effect of La carbonate differed from that of sevelamer-HCl in that it did not appear to exert its vascular effects via changes in oxidative stress or bone remodeling in the present model BACKGROUND Hyperphosphataemia in dialysis patients is associated with significant morbidity . We assessed the ability of lanthanum carbonate to control phosphate levels in patients undergoing haemodialysis or continuous ambulatory peritoneal dialysis ( CAPD ) in a short-term , placebo-controlled study . METHODS This was a double-blind , placebo-controlled , parallel-group study consisting of three phases : a 2 week washout period ; a 4 week , open-label , dose-titration phase ; and a 4 week , double-blind , placebo-controlled phase . After washout , patients ( n = 59 ) received lanthanum ( 375 mg/day ) , titrated up to a maintenance dose ( maximum : 2250 mg ) that achieved control of serum phosphate levels between 1.3 and 1.8 mmol/l ( 4.03 - 5.58 mg/dl ) . After titration , patients were r and omized to receive their maintenance dose of lanthanum ( n = 17 ) or placebo ( n = 19 ) for 4 weeks . Control of serum phosphate was the primary efficacy assessment . Levels of calcium , parathyroid hormone , calcium x phosphate product and lanthanum as well as adverse events were evaluated . RESULTS By the end of titration , 70 % of patients had serum phosphate levels < or = 1.8 mmol/l . Lanthanum carbonate continued to control serum phosphate levels in the double-blind phase . At the end of the study , 64.7 % of lanthanum carbonate-treated patients were controlled compared with 21.4 % in the placebo group . Results in patients receiving CAPD were similar to those seen in the group as a whole . Mean parathyroid hormone levels ( P = 0.41 ) and calcium x phosphate product ( P<0.001 ) were both higher in the placebo than the lanthanum carbonate group . CONCLUSIONS Lanthanum carbonate is an effective phosphate binder able to control serum phosphate and calcium x phosphate product Abstract Objective : Epidemiological data link elevated levels of serum phosphorus with increased mortality among patients with chronic kidney disease . Recent data also suggest improved survival with the use of dietary phosphate binders in patients on dialysis . However , few studies have comprehensively evaluated the survival benefit associated with different phosphate binders . A post-hoc survival analysis was undertaken of lanthanum carbonate ( Fosrenol * Fosrenol is a registered trademark of Shire Pharmaceuticals , Basingstoke , UK . ) versus st and ard therapy . Research design and methods : Patients on dialysis enrolled in a phase 3 , 2-year , comparative safety study were r and omized 1:1 to lanthanum carbonate or st and ard therapy to treat serum phosphorus to a target of ≤5.9 mg/dL ( 1.90 mmol/L ) . Patients ( N = 1354 ) were followed up for survival status during , or after completion of or discontinuation from the study . Main outcome measures : Survival was measured by time from first dose of study medication to all-cause mortality or last contact . Results : The distribution of follow-up time was similar in the lanthanum carbonate and st and ard therapy groups ( mean 23.7 versus 23.9 months [ median 27.0 versus 26.0 months ] , respectively ) . Serum phosphorus levels were similar across treatment groups , as patients were treated to target . At follow-up , 19.9 % ( 135/680 ) of patients treated with lanthanum carbonate had died versus 23.3 % ( 157/674 ) on st and ard therapy ( log-rank p = 0.18 ) . In the subgroup of patients aged > 65 years ( n = 336 ) , 27.0 % ( 44/163 ) of lanthanum-carbonate-treated patients had died compared with 39.3 % ( 68/173 ) on st and ard therapy ( log-rank p = 0.04 ) . Conclusion : In these survival analyses , overall mortality was similar in the lanthanum carbonate and st and ard therapy groups , but results suggest that there was a survival benefit associated with lanthanum carbonate treatment for patients aged > 65 years , who are likely to carry the greatest burden of vascular calcification . These results were similar to those observed in the Dialysis Clinical Outcomes Revisited study , a prospect i ve trial of sevelamer hydrochloride design ed to assess survival BACKGROUND Lanthanum carbonate ( LC ) is a non-calcium-containing phosphate binder and shows a comparable effect with other phosphate binders on hyperphosphatemia in dialysis patients . LC also contributes to a reduced oral calcium load compared with calcium carbonate ( CaC ) treatment . However , no crossover studies which compare the influence on serum calcium level between treatments with LC and CaC in hemodialysis ( HD ) patients have been carried out . METHODS After washout for 2 weeks , 50 patients on HD were r and omized ( 1 : 1 ) to receive LC or CaC for 3 months . Thereafter , patients underwent a second 2-week washout period and were switched to the alternative binder for the next 3 months . Mineral and bone metabolism markers were measured with the changes of vitamin D doses . RESULTS The serum phosphate level showed a similar decrease from baseline to 3 months in both groups . During the study periods , hypercalcemia was observed only in patients taking CaC. The dose of vitamin D analogue was increased more frequently in the patients of the LC group compared with LC group . The iPTH level showed a significant decrease in the CaC group , but not in the LC group . Serum levels of BAP , TRAP5b , and ALP were significantly elevated in the LC group , whereas the FGF-23 level showed a significant decrease . CONCLUSION LC effectively reduced the serum phosphate level ( like CaC ) and allowed the vitamin D analogue dosage to be increased without hypercalcemia in HD patients . LC is one of the useful phosphate binders without hypercalcemia . ( UMIN-CTR registration number : UMIN000002331 ) Treating hyperphosphatemia without increasing the calcium load in chronic kidney disease patients on dialysis is important , as conventional treatment frequently results in ectopic calcification . Sevelamer , a monotherapy for hyperphosphatemia is frequently associated with gastrointestinal disorders , often result ing in discontinuation of treatment . Lanthanum carbonate is a novel non-calcium-based phosphate binder for the treatment of chronic kidney disease . Here , its clinical efficacy and safety were assessed in Japanese dialysis patients . A placebo-controlled , r and omized , double-blind , parallel group , multicenter study was performed in Japanese dialysis patients . Patients were treated with various dosages of lanthanum carbonate or a placebo daily for six weeks . The primary efficacy endpoint was the change in serum phosphate level from the baseline . Secondary endpoints included achievement rates to target serum phosphate levels and changes in serum calcium levels . Safety was evaluated by the incidence of drug-related and treatment-emergent adverse events . A significant reduction in serum phosphate level was demonstrated for all dosages from Week 1 . This dose-dependent effect was also observed in the changes in serum calcium x phosphate product , yet there was no notable difference in serum calcium or serum intact parathyroid hormone levels . The incidence of drug-related adverse events was dose-dependent , with the most common being gastrointestinal symptoms . Lanthanum carbonate effectively controls serum phosphate levels and is generally tolerable to Japanese chronic kidney disease patients on dialysis , as reported for the Caucasian population . The optimal dosage in Japanese patients needs to be confirmed using a flexible-dose titration schedule BACKGROUND Lanthanum carbonate ( LC ) has been proposed as a new phosphate binder . Presented here are the results from one centre that participated in a multicentre trial to assess the effect of treatment with LC and calcium carbonate ( CC ) on the evolution of renal osteodystrophy in dialysis patients . Bone biopsies were performed at baseline , after 1 year of treatment and after a further 2-year follow-up period to assess the lanthanum concentration in bone and plasma . METHODS Twenty new dialysis patients were r and omized to receive LC ( median dose 1250 mg ) for 1 year ( n = 10 ) , followed by 2 years of CC treatment or CC ( n = 10 ) during the whole study period ( 3 years ) . RESULTS After 36 weeks of treatment , steady state was reached with plasma lanthanum levels varying around 0.6 ng/ml . Six weeks after cessation of 1 year of treatment , the plasma lanthanum levels declined to a value of 0.17 + /- 0.12 ng/ml ( P < 0.05 ) and after 2 years to 0.09 + /- 0.03 ng/ml . Plasma and bone lanthanum levels did not correlate with the average lanthanum dose at any time point . The mean bone concentration in patients receiving LC increased from 0.05 + /- 0.03 to 2.3 + /- 1.6 microg/g ( P < 0.05 ) after 1 year and slightly decreased at the end of the study to 1.9 + /- 1.6 microg/g ( P < 0.05 ) . CONCLUSIONS Bone deposition after 1 year of treatment with LC is low ( highest concentration : 5.5 microg/g ) . There is a slow release of lanthanum from its bone deposits 2 years after the discontinuation of the treatment and no association with aluminium-like bone toxicity BACKGROUND Several factors suggest that the presence of vascular calcification ( VC ) is associated with a high risk of cardiac events in uremic patients . The aim of this study was to analyze the influence of VC on cardiac morbidity and mortality in our hemodialysis ( HD ) patients . METHODS We studied 79 patients on HD : 43 males , mean age 48 + /- 15 years old , mean time on HD 83 + /- 63 months . The presence of VC was evaluated by radiologic series . Other cardiovascular risk factors analyzed were arterial hypertension , diabetes mellitus , obesity , cigarette smoking , anemia , and dyslipidemia . All patients underwent M-mode , two-dimensional , Doppler echocardiography . Patients were followed for two years . During this time , clinical information collected included predialysis blood pressure , incidence of ischemic heart disease , episodes of congestive heart failure , and mortality due to cardiovascular event . RESULTS VC was observed in 55.7 % of patients . Left ventricular hypertrophy , diastolic dysfunction , and cardiac valve calcification were significantly associated with VC . Ischemic heart disease ( 71.4 % vs. 28.6 % ) and episodes of cardiac failure ( 0.41 vs. 0.18 per year ; P < 0.05 ) appeared more frequently in the patient group with VC . VC was present in 80.6 % of patients who developed episodes of heart failure . Eight patients died from cardiac disease ; each of them had VC . CONCLUSION The presence of VC can help to identify those HD patients with a higher cardiovascular risk BACKGROUND AND OBJECTIVES Management of hyperphosphatemia , a predictor of mortality in chronic kidney disease , is challenging . Nonadherence to dietary phosphate binders , in part , contributes to uncontrolled serum phosphorus levels . This phase IIIb trial assessed the efficacy of increased dosages ( 3000 to 4500 mg/d ) of reformulated lanthanum carbonate ( 500- , 750- , and 1000-mg tablets ) in nonresponders to dosages of up to 3000 mg/d . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This 8-wk study with a 4-mo open-label extension enrolled 513 patients who were undergoing maintenance hemodialysis . Patients who achieved serum phosphorus control at week 4 with < or=3000 mg/d lanthanum carbonate entered cohort A ; nonresponders were r and omly assigned to receive 3000 , 3750 , or 4500 mg/d ( cohort B ) . The primary outcome measure was the control rate for predialysis serum phosphorus levels at the end of week 8 , among patients in cohort B. RESULTS At the end of week 4 , 54 % of patients achieved serum phosphorus control at dosages < or=3000 mg/d administered as one tablet per meal . Among patients who entered cohort B , control rates of 25 , 38 , and 32 % for patients who were r and omly assigned to 3000 , 3750 , or 4500 mg/d lanthanum carbonate , respectively , were achieved , with no increase in adverse events . Patients and physicians reported significantly higher levels of satisfaction with reformulated lanthanum carbonate compared with previous phosphate binders , partly because of reduced tablet burden with higher dosage strengths . Physicians and patients also expressed a preference for lanthanum carbonate over previous medication . CONCLUSIONS Reformulated lanthanum carbonate is an effective phosphate binder that may reduce daily tablet burden AIMS The aim of this crossover study was to compare the reduction of serum phosphorus ( SP ) with fixed doses of the non-calcium-containing phosphate binders lanthanum carbonate ( LC ) and sevelamer hydrochloride ( SH ) in hemodialysis patients . METHODS Following washout ( 2 - 3 weeks ) , 182 patients with SP > or= 6.0 mg/dl and calcium > or= 8.4 mg/dl were r and omized ( 1:1 ) to receive LC ( 2,250 to 3,000 mg/day ) or SH ( 4,800 to 6,400 mg/day ) for 4 weeks . Patients underwent a second washout ( 2 weeks ) and switched to the alternative binder for 4 weeks . RESULTS At the end of treatment , LC had reduced SP by 1.7 + /- 0.1 mg/dl , compared with 1.4 + /- 0.1 mg/dl for SH ; the difference was not statistically significant in the primary analysis ( LOCF , p = 0.133 ) . However , the reduction with LC was significantly greater than with SH in a prespecified key secondary analysis of patients who completed 4 weeks of treatment with each binder ( 0.5 mg/dl difference , p = 0.007 ) . The reduction of SP was also greater with LC than SH after 1 week of treatment ( p = 0.024 ) . CONCLUSIONS Although the primary analysis found no difference between LC and SH in the reduction of SP , a significant difference in favor of LC was observed in patients who completed treatment . The results of this study show interesting trends with respect to onset and duration of action that warrant further investigation in longer-term studies BACKGROUND Lanthanum carbonate is a highly effective phosphate binder with significant potential as a treatment for hyperphosphatemia in patients with end-stage renal disease ( ESRD ) . Here , the results of a placebo-controlled , dose-ranging study are presented . METHODS 196 patients ( > or = 18 years ) receiving hemodialysis for at least 6 months entered a 1- to 3-week , single-blind , placebo run-in phase . Of these , 145 patients were r and omized to a double-blind phase in which they received placebo or lanthanum carbonate in daily lanthanum doses of 225 , 675 , 1,350 or 2,250 mg for 6 weeks . Serum levels of phosphorus , calcium and parathyroid hormone , and adverse events were monitored throughout the study . RESULTS The intent-to-treat analysis ( n = 144 ) showed significant dose-related reductions in serum phosphorus at lanthanum doses of 675 , 1,350 and 2,250 mg . After 6 weeks of treatment , phosphorus levels were significantly lower in the lanthanum groups receiving 1,350 mg/day and 2,250 mg/day , compared with the placebo group ( respective changes from r and omization : -0.95 + /- 1.39 mg/dl ( -0.31 + /- 0.45 mmol/l ) , -1.13 + /- 2.01 mg/dl ( -0.36 + /- 0.65 mmol/l ) , 0.75 + /- 1.47 mg/dl ( 0.24 + /- 0.47 mmol/l ) , p < 0.001 ) . Significant reductions in serum phosphorus , compared with placebo , occurred in the lanthanum 1,350 mg/day group from the second week of treatment and in the 2,250 mg/day group from the first week of treatment . Adverse events were mainly gastrointestinal ( e.g. nausea and vomiting ) . Treatment-related adverse events occurred in 39 % of patients treated with lanthanum carbonate and 44 % of the placebo group . CONCLUSION Lanthanum carbonate is an effective and well-tolerated agent for the short-term treatment of hyperphosphatemia in patients with ESRD BACKGROUND Abnormalities in serum calcium , phosphorus , and parathyroid hormone ( PTH ) concentrations are common in patients with chronic kidney disease and have been associated with increased morbidity and mortality . No clinical trials have been conducted to clearly identify categories of calcium , phosphorus , and PTH levels associated with the lowest mortality risk . Current clinical practice guidelines are based largely on expert opinions , and clinical ly relevant differences exist among guidelines across countries . We sought to describe international trends in calcium , phosphorus , and PTH levels during 10 years and identify mortality risk categories in the Dialysis Outcomes and Practice Patterns Study ( DOPPS ) , an international study of hemodialysis practice s and associated outcomes . STUDY DESIGN Prospect i ve cohort study . PARTICIPANTS 25,588 patients with end-stage renal disease on hemodialysis therapy for longer than 180 days at 925 facilities in DOPPS I ( 1996 - 2001 ) , DOPPS II ( 2002 - 2004 ) , or DOPPS III ( 2005 - 2007 ) . PREDICTORS Serum calcium , albumin-corrected calcium ( Ca(Alb ) ) , phosphorus , and PTH levels . OUTCOMES Adjusted hazard ratios for all-cause and cardiovascular mortality calculated using Cox models . RESULTS Distributions of mineral metabolism markers differed across DOPPS countries and phases , with lower calcium and phosphorus levels observed in the most recent phase of DOPPS . Survival models identified categories with the lowest mortality risk for calcium ( 8.6 to 10.0 mg/dL ) , Ca(Alb ) ( 7.6 to 9.5 mg/dL ) , phosphorus ( 3.6 to 5.0 mg/dL ) , and PTH ( 101 to 300 pg/mL ) . The greatest risk of mortality was found for calcium or Ca(Alb ) levels greater than 10.0 mg/dL , phosphorus levels greater than 7.0 mg/dL , and PTH levels greater than 600 pg/mL and in patients with combinations of high-risk categories of calcium , phosphorus , and PTH . LIMITATIONS Because of the observational nature of DOPPS , this study can only indicate an association between mineral metabolism categories and mortality . CONCLUSIONS Our results provide important information about mineral metabolism trends in hemodialysis patients in 12 countries during a decade . The risk categories identified in the DOPPS cohort may be relevant to efforts at international harmonization of existing clinical guidelines for mineral metabolism AIMS To investigate the evolution of renal osteodystrophy in patients on maintenance dialysis , treated with lanthanum carbonate ( LC ) vs. st and ard phosphate-binder therapy ( Stx ) . MATERIAL S AND METHODS This was a 2-year , r and omized , prospect i ve , open-label study during which patients on dialysis received LC titrated to a maximum of 3,000 mg/day or their previous phosphate binder treatment with the aim to achieve target phosphorus levels of < or = 5.9 mg/dl . Paired bone biopsy sample s for histomorphometric analysis were available at baseline and 1 year ( LC 32 , Stx 33 ) , and at baseline and 2 years ( LC 32 , Stx 24 ) . RESULTS With similar phosphorus control , Stx was associated with numerically higher serum calcium levels at most visits . Results of osteocalcin and bone-specific alkaline phosphatase in LC patients were higher throughout the study and correlated with parameters of bone formation ; however , the differences were not significant . Histological changes in bone turnover and volume were analyzed with respect to normal ranges . There was an improvement in bone turnover in the LC group , which was significant in the 1-year group , and an improvement in bone volume which was significant in the 2-year group . No significant changes in bone turnover or bone volume were observed in the Stx groups . In the 2-year LC group , 1 patient had osteomalacia at baseline and end of therapy , and a mineralization defect developed in 2 other patients . Several possible factors for a mineralization defect were present in these patients , but no single cause could be clearly identified . Histomorphometric parameters of bone , including formation and mineralization , did not correlate with bone lanthanum . No mineralization defect was observed in the Stx groups . CONCLUSION These findings show that similar phosphorus control with Stx and LC results in higher bone turnover after 1 year and higher bone volume after 2 years with LC BACKGROUND The efficacy of lanthanum carbonate as a phosphate binder for the treatment of hyperphosphatemia has been reported , but not from a double-blind , comparator-controlled comparative study . METHODS The safety and efficacy of lanthanum carbonate and calcium carbonate on serum phosphate and calcium levels in Japanese hemodialysis patients were assessed by a r and omized , double-blind , comparator-controlled , parallel group , multicenter study . This study is the first study using a r and omized , double-blind method to compare lanthanum carbonate and calcium carbonate as phosphate binders . RESULTS In the double-blind phase , the changes in the serum phosphate level were similar in the lanthanum carbonate and calcium carbonate groups . The differences in the corrected serum calcium level or the calcium x phosphate products between the 2 groups were not statistically significant . However , the mean change in the corrected serum calcium level from baseline to the last outpatient visit was significantly lower in the lanthanum carbonate group than in the calcium carbonate group . The incidence of hypercalcemia in the lanthanum carbonate group was also significantly lower than in the calcium carbonate group . CONCLUSION Both compounds show similar efficacy on the serum phosphate level in patients undergoing hemodialysis when the dose is managed in a dose-variable and double-blind manner . However , lanthanum carbonate is superior in terms of lowering the incidence of hypercalcemia AIMS Sevelamer carbonate is an anion exchange resin with the same polymeric structure as sevelamer hydrochloride in which carbonate replaces chloride as the anion . The study investigated the effects of sevelamer carbonate and sevelamer hydrochloride on serum phosphorus , lipids and bicarbonate levels in hemodialysis patients . MATERIAL S AND METHODS This was a double-blind , r and omized , crossover study . 79 hemodialysis patients were r and omly assigned to either sevelamer carbonate or sevelamer hydrochloride for 8 weeks followed by a crossover to the other regimen for an additional 8 weeks of treatment . RESULTS The mean serum phosphorus was 4.6+/-0.9 and 4.7+/-0.9 mg/dl during sevelamer carbonate and sevelamer hydrochloride treatment , respectively . Sevelamer carbonate and sevelamer hydrochloride were equivalent in controlling serum phosphorus , the geometric least square mean ratio was 0.99 ( 90 % CI , 0.95 - 1.03 ) . Mean total and LDL cholesterol were 144.0+/-33.9 and 59.5+/-24.9 mg/dl , respectively , during sevelamer carbonate treatment and 139.0+/-33.6 and 56.0+/-23.3 mg/dl , respectively , during sevelamer hydrochloride treatment . Serum bicarbonate levels increased by 1.3+/-4.1 mEq/l during sevelamer carbonate treatment . There were fewer gastrointestinal adverse events with sevelamer carbonate . CONCLUSIONS Sevelamer carbonate and sevelamer hydrochloride were equivalent in controlling serum phosphorus and serum bicarbonate levels increased with sevelamer carbonate . Lipid profiles for both were well-below the levels suggested by KDOQI . Sevelamer carbonate may have advantages over sevelamer hydrochloride in the treatment of hyperphosphatemia in hemodialysis patients BACKGROUND Vascular calcification ( VC ) contributes to cardiovascular disease in haemodialysis ( HD ) patients . Few controlled studies have addressed interventions to reduce VC but non-calcium-based phosphate binders may be beneficial . No published r and omized study to date has assessed the effect of lanthanum carbonate ( LC ) on VC progression . METHODS We conducted a pilot r and omized controlled trial to determine the effect of LC on VC . Forty-five HD patients were r and omized to either LC or calcium carbonate ( CC ) . Primary outcome was change in aortic VC after 18 months . Secondary outcomes included superficial femoral artery ( SFA ) VC , bone mineral density ( BMD ) of lumbar spine and serum markers of mineral metabolism . At baseline , 6 and 18 month computed tomography was performed to measure VC and BMD . A r and om effect linear regression model was performed to assess differences . RESULTS Thirty patients completed the study ( 17 LC , 13 CC ) ; baseline median age 58 years , 38 % diabetic , 64 % male . Ninety-three per cent had aortic VC at commencement and 87 % showed progression . At 18 months , there was significantly less aortic VC progression with LC than CC ( adjusted difference -98.1 ( -149.4 , -46.8 ) Hounsfield units ( HU ) , P < 0.001 ) . There was also a non-significant reduction with LC in left SFA VC ( -25.8 ( -67.7 , 16.1 ) HU , P = 0.2 ) and right SFA VC ( -35.9 ( -77.8 , 5.9 ) HU , P = 0.09 ) . There was no difference in lumbar spine BMD and serum phosphate , calcium and parathyroid hormone levels between groups . Limitations to the study include small sample size and loss to follow up . CONCLUSIONS Lanthanum carbonate was associated with reduced progression of aortic calcification compared with CC in HD patients over 18 months BACKGROUND Hyperphosphataemia is a known independent risk factor for cardiovascular mortality . The objective of the study was to compare the effects of two phosphate binders , sevelamer carbonate and calcium carbonate on endothelial function ( EF ) and inflammation in patients on peritoneal dialysis ( PD ) with Type 2 diabetes mellitus ( T2DM ) . METHODS Fifteen subjects with hyperphosphataemia discontinued all phosphate binders to undergo a two-week washout and were assigned to sevelamer carbonate or calcium carbonate treatments for eight weeks . After a second two-week washout period , subjects crossed over to either of the alternate treatments for another eight weeks . At the beginning and end of each treatment , biomarkers of EF , pro-inflammatory cytokines , serum albumin , calcium , phosphate and lipids were measured . RESULTS Sevelamer carbonate significantly improved lipid profile compared with calcium carbonate . Amongst the EF and pro-inflammatory biomarkers , sevelamer carbonate decreased serum endothelin-1 , plasminogen activator inhibitor-1 , C-reactive protein and interleukin-6 . Both phosphate binders were effective in decreasing serum phosphate but sevelamer had a positive effect on EF . CONCLUSIONS Treatment with sevelamer carbonate has beneficial effects compared with calcium carbonate in decreasing inflammation and improving EF in patients with T2DM on PD BACKGROUND This multicenter , open-label , dose-titration study assessed the safety and efficacy of RenaGel(R ) , a nonabsorbed calcium- and aluminum-free phosphate binder , in lowering serum phosphorus . Secondary outcomes were its effects on serum intact parathyroid hormone ( iPTH ) and serum lipids . METHODS Phosphate binders were discontinued during a two-week washout period . Patients whose serum phosphorus was more than 6.0 mg/dl during washout were eligible for treatment . RenaGel(R ) , at starting doses of two , three , or four 440 mg capsules three times per day with meals , was administered to 172 hemodialysis patients for eight weeks . RenaGel(R ) could be increased by one capsule per meal every two weeks as necessary to achieve serum phosphorus control . A second two-week washout period followed . RESULTS Mean serum phosphorus rose from 6.8 + /- 2.0 mg/dl at prewashout to 9.1 + /- 2.4 mg/dl at the end of the washout period . It then declined to 6.6 + /- 1.9 mg/dl by the end of the eight-week RenaGel(R ) treatment period ( P < 0 . 0001 ) . Serum phosphorus increased to 8.0 + /- 2.2 mg/dl at the end of the second washout period . The mean dose at the end of RenaGel(R ) treatment was 5.4 g per day . Eighty-four percent of the patients previously used calcium-based phosphate binders . As expected , calcium declined during the initial washout period when calcium-based phosphate binders were discontinued . Mean serum calcium declined from 9.6 + /- 1.0 mg/dl at prewashout to 9.1 + /- 0.8 mg/dl after washout . It then increased to 9.4 + /- 0.9 mg/dl by the end of RenaGel(R ) treatment . Median serum iPTH increased during the two-week washout from 208 pg/ml to 316 pg/ml and then declined to 224 pg/ml at the end of the eight-week treatment period ( P < 0.0001 vs. end of initial washout ) . After eight weeks of treatment , RenaGel(R ) reduced mean serum total cholesterol from 171.0 + /- 43.1 mg/dl to 145.0 + /- 38.7 mg/dl ( P < 0.0001 ) and mean serum low-density lipoprotein cholesterol from 102.0 + /- 34.9 mg/dl to 75 . 6 + /- 29.4 mg/dl ( P < 0.0001 ) . High-density lipoprotein cholesterol , triglycerides , and serum albumin did not change . CONCLUSIONS RenaGel(R ) , a novel and calcium- plus aluminum-free effective phosphate binder , can control serum phosphorus and reduce the levels of PTH and cholesterol without inducing hypercalcemia or other side effects . Thus , this new phosphate binder may be effective in the treatment of renal osteodystrophy in uremic patients BACKGROUND AND OBJECTIVES Hyperphosphatemia and sub clinical endotoxemia are important sources of inflammation in HD . Proinflammatory cytokines are strong correlates of soluble CD14 ( sCD14 ) concentrations , an independent predictor of mortality in this population . We evaluated the effects of calcium acetate and sevelamer hydrochloride on serum inflammatory profile , endotoxin concentrations , and sCD14 levels in HD patients . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Prospect i ve , r and omized , open-label , parallel design trial . Fifty-nine stable HD patients , 30 receiving sevelamer , and 29 receiving calcium acetate were evaluated . Serum levels of inflammatory parameters ( high-sensitivity C-reactive protein [ hs-CRP ] , TNF-α , interleukin (IL)-1 , -6 , -10 , and -18 ) , as well as endotoxin and sCD14 concentrations , were measured at baseline and after 3 months of therapy . RESULTS Serum IL-6 increased in patients receiving calcium acetate , whereas hs-CRP and IL-6 significantly decreased in subjects treated with sevelamer , with IL-10 experiencing a trend to increase ( P = 0.052 ) . Serum endotoxin and sCD14 levels did not change after treatment with calcium acetate . However , these parameters decreased by 22.6 % and 15.2 % , respectively ( P < 0.01 ) , in patients receiving sevelamer . Multiple regression analysis showed that variation in serum endotoxin concentrations was the strongest factor associated with IL-6 change , whereas the only variables independently associated with changes in sCD14 levels were the variations in serum IL-6 and endotoxin concentrations . CONCLUSIONS Administration of the noncalcium phosphate binder sevelamer to maintenance HD patients is associated with a significant decrease in hs-CRP , IL-6 , serum endotoxin levels and sCD14 concentrations BACKGROUND Hyperphosphatemia is a common complication in end-stage renal disease ( ESRD ) patients . Reducing the serum phosphate level is crucial in management of ESRD . METHODS This study was a r and omized prospect i ve study , design ed to compare patients with hyperphosphatemia undergoing peritoneal dialysis while taking lanthanum carbonate or calcium carbonate . We divided 72 continuous ambulatory peritoneal dialysis ( CAPD ) patients whose serum phosphate levels were over 5.6 mg/dl into two groups to receive either lanthanum carbonate or calcium carbonate . Serum calcium , phosphate and PTH levels were examined serially for 24 weeks . RESULTS Both lanthanum carbonate and calcium carbonate reduced serum phosphate levels , from 6.79 ± 1.05 to 5.44 ± 1.44 and from 6.31 ± 1.13 to 4.74 ± 0.78 mg/dl , respectively . The calcium × phosphate product level was reduced in the lanthanum carbonate and calcium carbonate groups from 60.23 ± 10.23 to 46.97 ± 16.42 and from 57.92 ± 11.05 to 44.50 ± 7.74 mg2/dl2 , respectively . The serum parathyroid hormone ( PTH ) level in the lanthanum carbonate group did not change significantly compared to baseline during the study , but in the calcium carbonate group , the serum PTH level decreased significantly . Gastrointestinal complications were the main adverse effects of lanthanum carbonate and 11 out of 35 patients dropped out of the study due to this complication . CONCLUSIONS Lanthanum carbonate was as effective as calcium carbonate in reducing serum phosphate level , and serum PTH level tended to be steadier in the lanthanum carbonate group compared to the calcium carbonate group . Though the ifference was not significant , lanthanum carbonate tended not to elevate serum calcium level in CAPD patients compared to calcium carbonate . The high incidence of gastrointestinal adverse effect in the lanthanum carbonate group will need further evaluation Current phosphate binders used in hemodialysis patients include calcium-based binders that result in frequent hypercalcemia and aluminum-based binders that result in total body aluminum accumulation over time . This investigation describes the use of a calcium- and aluminum-free phosphate-binding polymer in hemodialysis patients and compares it with a st and ard calcium-based phosphate binder . An open-label , r and omized , crossover study was performed to evaluate the safety and effectiveness of sevelamer hydrochloride in controlling hyperphosphatemia in hemodialysis patients . After a 2-week phosphate binder washout period , stable hemodialysis patients were administered either sevelamer or calcium acetate , and the dosages were titrated upward to achieve improved phosphate control over an 8-week period . After a 2-week washout period , patients crossed over to the alternate agent for 8 weeks . Eighty-four patients from eight centers participated in the study . There was a similar decrease in serum phosphate values over the course of the study with both sevelamer ( -2.0 + /- 2.3 mg/dL ) and calcium acetate ( -2.1 + /- 1.9 mg/dL ) . Twenty-two percent of patients developed a serum calcium greater than 11.0 mg/dL while receiving calcium acetate , versus 5 % of patients receiving sevelamer ( P < 0.01 ) . The incidence of hypercalcemia for sevelamer was not different from the incidence of hypercalcemia during the washout period . Patients treated with sevelamer also sustained a 24 % mean decrease in serum low-density lipoprotein cholesterol levels . Sevelamer was effective in controlling hyperphosphatemia without result ing in an increase in the incidence of hypercalcemia seen with calcium acetate . This agent appears quite effective in the treatment of hyperphosphatemia in hemodialysis patients , and its usage may be advantageous in the treatment of dialysis patients Background / Aims : Hyperphosphatemia is an important clinical consequence of renal failure , and its multiple adverse systemic effects are associated with significantly increased risks of morbidity and mortality in dialysis patients . Existing oral phosphate binders have not permitted control of serum phosphate within currently accepted guidelines . This study compares lanthanum carbonate with calcium carbonate for control of serum phosphate in hemodialysis patients . Methods : In this European multicentre study , 800 patients were r and omised to receive either lanthanum or calcium carbonate and the dose titrated over 5 weeks to achieve control of serum phosphate . Serum levels of phosphate , calcium and parathryoid hormone were followed over the following 20 weeks . Results : Around 65 % of patients in each group achieved phosphate control , but in the calcium carbonate group this was at the expense of significant hypercalcemia ( 20.2 % of patients vs. 0.4 % ) . Consequently , calcium x phosphate product tended to be better controlled in the lanthanum group . Conclusion : This 6-month study demonstrates that serum phosphate control with lanthanum carbonate ( 750–3,000 mg/day ) is similar to that seen with calcium carbonate ( 1,500–9,000 mg/day ) , but with a significantly reduced incidence of hypercalcemia . Lanthanum carbonate is well tolerated and may be more effective in reducing calcium x phosphate product than calcium carbonate BACKGROUND Lanthanum carbonate is a novel , non-calcium , non-aluminum phosphate binder under evaluation for the treatment of hyperphosphatemia in end-stage renal disease ( ESRD ) patients receiving either hemodialysis or continuous ambulatory peritoneal dialysis . METHODS This 16-week study assessed the control of serum phosphorus with lanthanum carbonate , and its effects on serum calcium , calcium x phosphorus product , and parathyroid hormone ( PTH ) . Hemodialysis patients > or = 18 years old entered into a 1- to 3-week washout period during which serum phosphorus levels rose to > 5.9 mg/dL ( 1.90 mmol/L ) . In total , 126 patients were titrated with lanthanum carbonate at doses containing 375 , 750 , 1,500 , 2,250 , or 3,000 mg/d elemental lanthanum , given in divided doses with meals over a 6-week period , to achieve serum levels < or = 5.9 mg/dL. By the end of dose titration , 11/126 ( 9 % ) patients received < or = 750 mg/d of lanthanum , 25 ( 20 % ) received 1,500 mg/d , 37 ( 29 % ) received 2,250 mg/d , and 53 ( 42 % ) received 3,000 mg/d . Following titration , patients were r and omized to receive either lanthanum carbonate or placebo during a 4-week , double-blind maintenance phase . RESULTS At the study endpoint , the mean difference in serum phosphorus between the lanthanum carbonate and placebo treatment arms was 1.91 mg/dL ( 0.62 mmol/L ) ( P < 0.0001 ) . Calcium x phosphorus product ( P < 0.0001 ) and serum PTH levels ( P < 0.01 ) were also significantly lower with lanthanum carbonate versus placebo . The incidence of drug-related adverse events was similar between placebo- and lanthanum carbonate-treated patients . CONCLUSION Lanthanum carbonate is an effective and well-tolerated agent for the treatment of hyperphosphatemia in patients with ESRD BACKGROUND Lanthanum carbonate ( LC ) ( Fosrenol ) is a novel new treatment for hyperphosphatemia . In this phase III , open-label study , we compared the effects of LC and calcium carbonate ( CC ) on the evolution of renal osteodystrophy ( ROD ) in dialysis patients . METHODS Ninety-eight patients were r and omized to LC ( N = 49 ) or CC ( N = 49 ) . Bone biopsies were taken at baseline and after one year of treatment . Acceptable paired biopsies were available for static and dynamic histomorphometry studies in 33 LC and 30 CC patients . Blood sample s were taken at regular intervals for biochemical analysis and adverse events were monitored . RESULTS LC was well tolerated and serum phosphate levels were well controlled in both treatment groups . The incidence of hypercalcemia was lower in the LC group ( 6 % vs. 49 % for CC ) . At baseline , subtypes of ROD were similarly distributed in both groups , with mixed ROD being most common . At one-year follow-up in the LC group , 5 of 7 patients with baseline low bone turnover ( either adynamic bone or osteomalacia ) , and 4 of 5 patients with baseline hyperparathyroidism , had evolved toward a normalization of their bone turnover . Only one lanthanum-treated patient evolved toward adynamic bone compared with 6 patients in the CC group . In the LC group , the number of patients having either adynamic bone , osteomalacia , or hyperpara decreased overall from 12 ( 36 % ) at baseline to 6 ( 18 % ) , while in the calcium group , the number of patients with these types of ROD increased from 13 ( 43 % ) to 16 ( 53 % ) . CONCLUSION LC is a poorly absorbed , well-tolerated , and efficient phosphate binder . LC-treated dialysis patients show almost no evolution toward low bone turnover over one year ( unlike CC-treated patients ) , nor do they experience any aluminum-like effects on bone Elevated serum phosphorus and calcium are associated with arterial calcification and mortality in dialysis patients . Unlike calcium-based binders , sevelamer attenuates arterial calcification but it is unknown whether sevelamer affects mortality or morbidity . In a multicenter , r and omized , open-label , parallel design trial we compared sevelamer and calcium-based binders on all-cause and cause-specific mortality ( cardiovascular , infection , and other ) in prevalent hemodialysis patients . A total of 2103 patients were initially r and omized to treatment and 1068 patients completed the study . All-cause mortality rates and cause-specific mortality rates were not significantly different . There was a significant age interaction on the treatment effect . Only in patients over 65 years of age was there a significant effect of sevelamer in lowering the mortality rate . There was a suggestion that sevelamer was associated with lower overall , but not cardiovascular-linked , mortality in older patients . We suggest that further research is needed to confirm these findings Insufficient control of serum calcium and phosphate levels in patients undergoing hemodialysis is associated with increased mortality . As commonly used calcium-containing phosphate binders can cause arterial calcification , newly developed calcium-free phosphate binders , such as sevelamer hydrochloride ( SH ) and lanthanum carbonate ( LC ) , have received much attention . We assessed the efficacy and safety of SH and LC treatment in Japanese patients undergoing hemodialysis in a prospect i ve r and omized open blinded endpoint ( PROBE ) crossover study . Forty-two patients were r and omized to receive SH or LC for 13 weeks , with the dosages adjusted every 2 weeks , followed by treatment with the other drug for another 13 weeks . The average daily doses of SH and LC were 2971 ± 1464 mg and 945 ± 449 mg , respectively . The mean dosage ratio of SH to LC was 3.05 , which was maintained throughout the treatment period . SH and LC were similarly effective at controlling serum calcium and phosphate levels in the majority of patients ( 78 - 93 % ) . A few serious adverse events ( AEs ) involving the biliary system occurred during the LC treatment period , but they were not considered to be treatment-induced . Although the incidence of constipation , the most common treatment-related AE , was higher during the SH period ( 27 % vs. 5 % ; P < 0.05 ) , no difference was observed in total treatment-related AEs . This study demonstrates that SH and LC are comparable treatments for controlling serum phosphate and calcium levels , and that both compounds are safe and well-tolerated in Japanese patients undergoing hemodialysis BACKGROUND AND OBJECTIVES Increased inflammation and oxidative stress may be caused by proteins and lipids modified by cytotoxic advanced glycation end products ( AGEs ) in food . Restricting food containing elevated AGEs improves these risk factors in diabetic CKD . Because diet adherence can be problematic , this study aim ed to remove cytotoxic AGEs from food already ingested and to determine whether sevelamer carbonate sequesters cytotoxic AGEs in the gut , preventing their uptake and thereby reducing AGE-induced abnormalities . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This single-center , r and omized , 2-month , open-label , intention-to-treat , crossover study compared sevelamer carbonate with calcium carbonate treatment in stage 2 - 4 diabetic CKD . Participants received 2 months of treatment with one drug , had a 1-week washout , and then received the opposite drug for 2 months . RESULTS Sevelamer carbonate reduced HbA1c , serum methylglyoxal , serum (ε)N-carboxymethyl-lysine , triglycerides , and 8-isoprostanes . Total cholesterol and fibroblast growth factor 23 were reduced by sevelamer carbonate , relative to calcium carbonate . AGE receptor 1 and sirtuin 1 mRNA were increased and PMNC TNFα levels were decreased by sevelamer carbonate , but not calcium carbonate . Medications and caloric and AGE intake remained unchanged . Sevelamer carbonate reversibly bound AGE-BSA at intestinal , but not stomach , pH. CONCLUSIONS Sevelamer carbonate significantly reduces HbA1c , fibroblast growth factor 23 , lipids , and markers of inflammation and oxidative stress , and markedly increases antioxidant markers , independently of phosphorus in patients with diabetes and early kidney disease . These novel actions of sevelamer carbonate on metabolic and inflammatory abnormalities in type 2 diabetes mellitus may affect progression of early diabetic CKD Background / Aims : Lanthanum carbonate ( LC , FOSRENOL ® ) is an effective phosphate binder for which tolerability and a safety profile have been reported in haemodialysis patients . Patients from previous studies entered a 2-year extension , enabling assessment of efficacy and safety for up to 6 years of LC monotherapy . Methods : Patients from four previous trials entered this study . Results : Ninety-three patients started the extension , with 22 entering a sixth year of LC treatment . Two-thirds of all patients received LC doses of 2,250 or 3,000 mg/day . Reductions in serum phosphate and calcium × phosphate product were maintained for up to 6 years . There were no new or unexpected adverse events ( AEs ) , and no increase in the incidence of events with increasing treatment exposure . Over the complete duration of therapy , treatment-related AEs occurred in 25.8 % of patients and were primarily gastrointestinal in nature . No clinical ly relevant changes in liver function tests were observed and there was no evidence of adverse effects on the liver , bone or the central nervous system . Conclusions : LC monotherapy was effective and well tolerated for up to 6 years with no evidence of safety concerns or increased frequency of AEs |
12,981 | 26,771,169 | There was evidence of benefits for liaison psychiatry teams in improving service-related outcomes in emergency departments , but this was often limited by potential confounding in most studies .
There was limited evidence regarding models to improve urgent and emergency access to crisis care to guide police officers in their Mental Health Act responsibilities .
There was positive evidence on clinical effectiveness and cost-effectiveness of crisis resolution teams but variability in implementation .
There was a large evidence base on promoting recovery with a range of interventions recommended by NICE likely to be important in helping people stay well . | BACKGROUND Crisis Concordat was established to improve outcomes for people experiencing a mental health crisis .
The Crisis Concordat sets out four stages of the crisis care pathway : ( 1 ) access to support before crisis point ; ( 2 ) urgent and emergency access to crisis care ; ( 3 ) quality treatment and care in crisis ; and ( 4 ) promoting recovery .
OBJECTIVES To evaluate the clinical effectiveness and cost-effectiveness of the models of care for improving outcomes at each stage of the care pathway .
Current work from the Crisis resolution team Optimisation and RElapse prevention study aims to improve fidelity in delivering these models . | Background Compulsory admission to psychiatric hospitals may be distressing , disruptive to patients and families , and associated with considerable cost to the health service . Improved patient experience and cost reductions could be realised by providing cost-effective crisis planning services . Methods Economic evaluation within a multi-centre r and omised controlled trial comparing Joint Crisis Plans ( JCP ) plus treatment as usual ( TAU ) to TAU alone for patients aged over 16 , with at least one psychiatric hospital admission in the previous two years and on the Enhanced Care Programme Approach register . JCPs , containing the patient 's treatment preferences for any future psychiatric emergency , are a form of crisis intervention that aim to mitigate the negative consequences of relapse , including hospital admission and use of coercion . Data were collected at baseline and 18-months after r and omisation . The primary outcome was admission to hospital under the Mental Health Act . The economic evaluation took a service perspective ( health , social care and criminal justice services ) and a societal perspective ( additionally including criminal activity and productivity losses ) . Findings The addition of JCPs to TAU had no significant effect on compulsory admissions or total societal cost per participant over 18-months follow-up . From the service cost perspective , however , evidence suggests a higher probability ( 80 % ) of JCPs being the more cost-effective option . Exploration by ethnic group highlights distinct patterns of costs and effects . Whilst the evidence does not support the cost-effectiveness of JCPs for White or Asian ethnic groups , there is at least a 90 % probability of the JCP intervention being the more cost-effective option in the Black ethnic group . Interpretation The results by ethnic group are sufficiently striking to warrant further investigation into the potential for patient gain from JCPs among black patient groups . Trial Registration Current Controlled Trials IS RCT BACKGROUND Psychiatric emergency situations ( PES ) are of high importance to the German prehospital physician-based emergency medical system . So far , however , no prospect i ve studies regarding the incidence of PES have been performed , neither have effects of training programs on diagnostic and therapeutic accuracy been studied . METHOD The protocol s of two emergency medical services ( EMS ) were collected and analyzed prospect ively . Emergency physicians ( EPs ) in Kaiserslautern ( KL ) attended a st and ardized educational program and underwent daily supervision . EPs in Homburg ( HOM ) had not been informed about the study . In KL , sociodemographic variables were collected . An investigator who was not involved in the individual EMS mission assessed the correct classification of PES . RESULTS Among all calls for an EP , 11.8 % were classified as PES . There was no difference between the two centers . Correct classification of PES in KL was significantly higher than that in HOM ( 94.3 % vs. 80.6 % ) . Documentation of suicidal behavior was deficient in both centers . EPs in KL gave verbal crisis intervention significantly more often , administered less medication overall , and dispensed more specific drugs in psychotic disorders and significantly less drugs in substance abuse disorders . Patients were more often treated at the scene and were less often transported to a hospital . Some sociodemographic variables were associated with psychiatric morbidity of treatment . CONCLUSION Accounting for 12 % of all missions , psychiatric emergencies are a frequent reason for calls for EPs , equaling trauma-related and neurological emergencies . The most frequent reasons for calls were alcohol intoxication , states of agitation and suicidal behavior . The diagnostic and therapeutic accuracy of EPs may be improved with a concise st and ardized teaching program BACKGROUND Women 's crisis houses have been developed in the UK as a less stigmatising and less institutional alternative to traditional psychiatric wards . AIMS To examine the effectiveness and cost-effectiveness of women 's crisis houses by first examining the feasibility of a pilot patient-preference r and omised controlled trial ( PP- RCT ) design ( IS RCT N20804014 ) . METHOD We used a PP- RCT study design to investigate women presenting in crisis needing informal admission . The four study arms were the patient preference arms of women 's crisis house or hospital admission , and r and omised arms of women 's crisis house or hospital admission . RESULTS Forty-one women entered the r and omised arms of the trial ( crisis house n = 19 , wards n = 22 ) and 61 entered the patient-preference arms ( crisis house n = 37 , ward n = 24 ) . There was no significant difference in outcomes ( symptoms , functioning , perceived coercion , stigma , unmet needs or quality of life ) or costs for any of the groups ( r and omised or preference arms ) , but women who obtained their preferred intervention were more satisfied with treatment . CONCLUSIONS Although the sample sizes were too small to allow definite conclusions , the results suggest that when services are able to provide interventions preferred by patients , those patients are more likely to be satisfied with treatment . This pilot study provides some evidence that women 's crisis houses are as effective as traditional psychiatric wards , and may be more cost-effective Background : A&E departments are key points of contact for many people with mental health problems . Various models of care have been developed in A&E departments for delivering mental health services , but few have been assessed for effectiveness . The present study aim ed to assess the impact of a dedicated A&E psychiatric nurse service on several outcomes relevant to patients and clinicians . Methods : A crossover design was used to introduce a dedicated psychiatric nurse service ( comprising four experienced community psychiatric nurses ) into two busy UK A&E departments . St and ardised assessment s were completed for each patient , and a r and om sample of these independently assessed for quality . Data were also collected on the number of patients assessed , psychiatric nurse time employed , waiting times , onward referrals , repeat attendances , patient satisfaction , and staff views . Results : A&E staff referred about a third of patients judged to have mental health problems to the psychiatric nurse service ; approximately half of those assessed had a psychiatric history . On average , assessment s took 60 min and over 90 % of the formulated management plans were judged appropriate by independent assessors . The psychiatric nurse intervention had little impact on waiting times or satisfaction levels for mental health patients , although there was evidence of a change in onward referral patterns . Comment : Psychiatric nurse assessment services have been introduced in many A&E departments , although the evidence base for the effectiveness of this development is not well established . This study presents evidence that psychiatric nurses can provide an accurate assessment and referral service with advantages for patient care Background Mental health patients can feel anxious about losing the support of staff and patients when discharged from hospital and often discontinue treatment , experience relapse and readmission to hospital , and sometimes attempt suicide . The benefits of peer support in mental health services have been identified in a number of studies with some suggesting clinical and economic gains in patients being discharged . Methods This pilot r and omised controlled trial with economic evaluation aim ed to explore whether peer support in addition to usual aftercare for patients during the transition from hospital to home would increase hope , reduce loneliness , improve quality of life and show cost effectiveness compared with patients receiving usual aftercare only , with follow-up at one and three-months post-discharge . Results A total of 46 service users were recruited to the study ; 23 receiving peer support and 23 in the care-as-usual arm . While this pilot trial found no statistically significant benefits for peer support on the primary or secondary outcome measures , there is an indication that hope may be further increased in those in receipt of peer support . The total cost per case for the peer support arm of the study was £ 2154 compared to £ 1922 for the control arm . The mean difference between costs was minimal and not statistically significant . However , further analyses demonstrated that peer support has a reasonably high probability of being more cost effective for a modest positive change in the measure of hopelessness . Challenges faced in recruitment and follow-up are explored alongside limitations in the delivery of peer support . Conclusions The findings suggest there is merit in conducting further research on peer support in the transition from hospital to home consideration should be applied to the nature of the patient population to whom support is offered ; the length and frequency of support provided ; and the contact between peer supporters and mental health staff . There is no conclusive evidence to support the cost effectiveness of providing peer support , but neither was it proven a costly intervention to deliver . The findings support an argument for a larger scale trial of peer support as an adjunct to existing services . Trial registration Current Controlled Trials IS RCT OBJECTIVE In spite of much effort to create guidelines on the management of violent behavior ( VB ) in emergency departments , little is known about the impact of such guidelines on a real-life emergency environment . The aim of this study is to investigate the impact of a staff educational crisis intervention ( SECI ) on the reduction of VB in patients admitted to emergency departments following drug suicidal attempt . METHOD The impact of a SECI on VB of patient consulting the ER following a drug suicide attempt was assessed by comparing the occurrence of VB before ( 5 months ) and after ( 5 months ) the introduction of a SECI . RESULTS A significant reduction in VB ( from 17.32 % to 7.14 % ) was found with the comparison of two 5-month periods : before ( 254 patients ) and after ( 224 patients ) the introduction of a SECI program ( chi(2)=11.238 ; P=.0008 ) . CONCLUSION These preliminary data suggest the need for further prospect i ve r and omized studies aim ing to prevent VB in emergency departments by developing specific SECI programs Abstract Objective To investigate whether a form of advance agreement for people with severe mental illness can reduce the use of inpatient services and compulsory admission or treatment . Design Single blind r and omised controlled trial , with r and omisation of individual patients . The investigator was blind to allocation . Setting Eight community mental health teams in southern Engl and . Participants 160 people with an operational diagnosis of psychotic illness or non-psychotic bipolar disorder who had experienced a hospital admission within the previous two years . Intervention The joint crisis plan was formulated by the patient , care coordinator , psychiatrist , and project worker and contained contact information , details of mental and physical illnesses , treatments , indicators for relapse , and advance statements of preferences for care in the event of future relapse . Main outcome measures Admission to hospital , bed days , and use of the Mental Health Act over 15 month follow up . Results Use of the Mental Health Act was significantly reduced for the intervention group , 13 % ( 10/80 ) of whom experienced compulsory admission or treatment compared with 27 % ( 21/80 ) of the control group ( risk ratio 0.48 , 95 % confidence interval 0.24 to 0.95 , P = 0.028 ) . As a consequence , the mean number of days of detention ( days spent as an inpatient while under a section of the Mental Health Act ) for the whole intervention group was 14 compared with 31 for the control group ( difference 16 , 0 to 36 , P = 0.04 ) . For those admitted under a section of the Mental Health Act , the number of days of detention was similar in the two groups ( means 114 and 117 , difference 3 , −61 to 67 , P = 0.98 ) . The intervention group had fewer admissions ( risk ratio 0.69 , 0.45 to 1.04 , P = 0.07 ) . There was no evidence for differences in bed days ( total number of days spent as an inpatient ) ( means 32 and 36 , difference 4 , −18 to 26 , P = 0.15 for the whole sample ; means 107 and 83 , difference −24 , −72 to 24 , P = 0.39 for those admitted ) . Conclusions Use of joint crisis plans reduced compulsory admissions and treatment in patients with severe mental illness . The reduction in overall admission was less . This is the first structured clinical intervention that seems to reduce compulsory admission and treatment in mental health services BACKGROUND People with borderline personality disorder frequently experience crises . To date , no r and omised controlled trials ( RCTs ) of crisis interventions for this population have been published . AIMS To examine the feasibility of recruiting and retaining adults with borderline personality disorder to a pilot RCT investigating the potential efficacy and cost-effectiveness of using a joint crisis plan . METHOD An RCT of joint crisis plans for community-dwelling adults with borderline personality disorder ( trial registration : IS RCT N12440268 ) . The primary outcome measure was the occurrence of self-harming behaviour over the 6-month period following r and omisation . Secondary outcomes included depression , anxiety , engagement and satisfaction with services , quality of life , well-being and cost-effectiveness . RESULTS In total , 88 adults out of the 133 referred were eligible and were r and omised to receive a joint crisis plan in addition to treatment as usual ( TAU ; n = 46 ) or TAU alone ( n = 42 ) . This represented approximately 75 % of our target sample size and follow-up data were collected on 73 ( 83.0 % ) participants . Intention-to-treat analysis revealed no significant differences in the proportion of participants who reported self-harming ( odds ratio ( OR ) = 1.9 , 95 % CI 0.53 - 6.5 , P = 0.33 ) or the frequency of self-harming behaviour ( rate ratio ( RR ) = 0.74 , 95 % CI 0.34 - 1.63 , P = 0.46 ) between the two groups at follow-up . No significant differences were observed between the two groups on any of the secondary outcome measures or costs . CONCLUSIONS It is feasible to recruit and retain people with borderline personality disorder to a trial of joint crisis plans and the intervention appears to have high face validity with this population . However , we found no evidence of clinical efficacy in this feasibility study BACKGROUND The CRIMSON ( CRisis plan IMpact : Subjective and Objective coercion and eNgagement ) study is an individual level , r and omised controlled trial that compared the effectiveness of Joint Crisis Plans ( JCPs ) with treatment as usual for people with severe mental illness . The JCP is a negotiated statement by a patient of treatment preferences for any future psychiatric emergency , when he or she might be unable to express clear views . We assessed whether the additional use of JCPs improved patient outcomes compared with treatment as usual . METHODS Patients were eligible if they had at least one psychiatric admission in the previous 2 years and were on the Enhanced Care Programme Approach register . The study was done with 64 generic and specialist community mental health teams in four English mental health care provider organisations ( trusts ) . Hypotheses tested were that , compared with the control group , the intervention group would experience : fewer compulsory admissions ( primary outcome ) ; fewer psychiatric admissions ; shorter psychiatric stays ; lower perceived coercion ; improved therapeutic relationships ; and improved engagement . We stratified participants by centre . The research team but not participants nor clinical staff were masked to allocation . This study is registered with Clinical Trials.gov , number IS RCT N11501328 . FINDINGS 569 participants were r and omly assigned ( 285 to the intervention group and 284 to the control group ) . No significant treatment effect was seen for the primary outcome ( 56 [ 20 % ] sectioned in the control group and 49 [ 18 % ] in the JCP group ; odds ratio 0·90 [ 95 % CI 0·58 - 1·39 , p=0·63 ] ) or any secondary outcomes , with the exception of an improved secondary outcome of therapeutic relationships ( 17·3 [ 7·6 ] vs 16·0 [ 7·1 ] ; adjusted difference -1·28 [ 95 % CI -2·56 to -0·01 , p=0·049 ] ) . Qualitative data supported this finding . INTERPRETATION Our findings are inconsistent with two earlier JCP studies , and show that the JCP is not significantly more effective than treatment as usual . There is evidence to suggest the JCPs were not fully implemented in all study sites , and were combined with routine clinical review meetings which did not actively incorporate patients ' preferences . The study therefore raises important questions about implementing new interventions in routine clinical practice . FUNDING Medical Research Council UK and the National Institute for Health Research Background Acute psychiatric wards manage patients whose actions may threaten safety ( conflict ) . Staff act to avert or minimise harm ( containment ) . The Safewards model enabled the identification of ten interventions to reduce the frequency of both . Objective To test the efficacy of these interventions . Design A pragmatic cluster r and omised controlled trial with psychiatric hospitals and wards as the units of r and omisation . The main outcomes were rates of conflict and containment . Participants Staff and patients in 31 r and omly chosen wards at 15 r and omly chosen hospitals . Results For shifts with conflict or containment incidents , the experimental condition reduced the rate of conflict events by 15 % ( 95 % CI 5.6–23.7 % ) relative to the control intervention . The rate of containment events for the experimental intervention was reduced by 26.4 % ( 95 % CI 9.9–34.3 % ) . Conclusions Simple interventions aim ing to improve staff relationships with patients can reduce the frequency of conflict and containment . Trial registration IRSCTN38001825 The mental health liaison nurse role in the emergency department ( ED ) has demonstrated a range of positive outcomes for both consumers and staff . In Australia , the added value associated with establishing mental health nurse practitioner ( MHNP ) positions based on this model is emerging . This paper presents qualitative findings from a study using a mixed- method design to evaluate an ED-based MHNP outpatient service in Sydney , Australia . In evaluating this new service , semistructured interviews were conducted with a r and om selection of study participants and a stratified sample of ED staff . This is the first of a two-part paper that presents an analysis of qualitative data from interviews conducted with study participants ( n = 23 ) . Participants reported numerous therapeutic benefits from the service , such as support , underst and ing , and a focus on solutions rather than problems , and high levels of satisfaction with the accessibility of the service and follow up . Suggestions for improving the service were also offered . Participants emphasized that overall ED service provision would be enhanced through additional re sources , especially an extension of operating hours . Findings from these participant interviews provide strong support for an ED-based MHNP outpatient service |
12,982 | 29,485,314 | Careful messaging and the use of scripts/role play ( Promotion ) were recommended .
The need for intensive re sources and gatekeeping by professionals were barriers while having research staff on-site and lead clinician support ( Working with Partners ) was advocated .
The findings of this review are applicable to all palliative care research and not just r and omised controlled trials | Background : Effective recruitment to r and omised controlled trials is critically important for a robust , trustworthy evidence base in palliative care .
Many trials fail to achieve recruitment targets , but the reasons for this are poorly understood .
Underst and ing barriers and facilitators is a critical step in design ing optimal recruitment strategies .
Aim : To identify , explore and synthesis e knowledge about recruitment barriers and facilitators in palliative care trials using the ‘ 6 Ps ’ of the ‘ Social Marketing Mix Framework ’ . | Background A commonly reported problem with the conduct of multicentre r and omised controlled trials ( RCTs ) is that recruitment is often slower or more difficult than expected , with many trials failing to reach their planned sample size within the timescale and funding originally envisaged . The aim of this study was to explore factors that may have been associated with good and poor recruitment in a cohort of multicentre trials funded by two public bodies : the UK Medical Research Council ( MRC ) and the Health Technology Assessment ( HTA ) Programme . Methods The cohort of trials was identified from the administrative data bases held by the two funding bodies . 114 trials that recruited participants between 1994 and 2002 met the inclusion criteria . The full scientific applications and subsequent trial reports su bmi tted by the trial teams to the funders provided the principal data sources . Associations between trial characteristics and recruitment success were tested using the Chi-squared test , or Fisher 's exact test where appropriate . Results Less than a third ( 31 % ) of the trials achieved their original recruitment target and half ( 53 % ) were awarded an extension . The proportion achieving targets did not appear to improve over time . The overall start to recruitment was delayed in 47 ( 41 % ) trials and early recruitment problems were identified in 77 ( 63 % ) trials . The inter-relationship between trial features and recruitment success was complex . A variety of strategies were employed to try to increase recruitment , but their success could not be assessed . Conclusion Recruitment problems are complex and challenging . Many of the trials in the cohort experienced recruitment difficulties . Trials often required extended recruitment periods ( sometimes supported by additional funds ) . While this is of continuing concern , success in addressing the trial question may be more important than recruitment alone R and omized controlled trials ( RCTs ) in palliative cancer care often experience method ological problems . In this paper we discuss issues of major concern , including recruitment , patient attrition and compliance , arising from an RCT that compared comprehensive palliative care to conventional care . The main criteria for trial entry were incurable malignant disease and a survival expectancy of between 2 and 9 months . Patients ' health-related quality of life ( HRQL ) , self-assessed by multi-item question naires , was a defined endpoint . The planned number of patients was successfully recruited , although the patients were referred late in the course of their disease so that follow-up tended to be short . Compliance in completing HRQL question naires was good up to 1 month before the patient 's death ; but in the final weeks it was found to drop substantially . Based on our experience , recommendations are given for those planning similar research . Procedures for improving patient recruitment are suggested , stressing the need for local data management , repeated information to referral sources , extensive screening for potentially eligible patients and simple referral routines . Precise inclusion criteria , including prognostic factors other than physicians ' estimates of life expectancy , should be used to ensure a sufficient follow-up period . For HRQL assessment , multi-item question naires can achieve excellent compliance up to 1 month before patients ' death , but in order to evaluate the very final weeks of life we recommend the use of simpler methods OBJECTIVE Little is known about the effectiveness of advance care planning in the United Kingdom , although policy documents recommend that it should be available to all those with life-limiting illness . METHOD An exploratory patient preference r and omized controlled trial of advance care planning discussion s with an independent mediator ( maximum three sessions ) was conducted in London outpatient oncology clinics and a nearby hospice . Seventy-seven patients ( mean age 62 years , 39 male ) with various forms of recurrent progressive cancer participated , and 68 ( 88 % ) completed follow-up at 8 weeks . Patients completed visual analogue scales assessing perceived ability to discuss end-of-life planning with healthcare professionals or family and friends ( primary outcome ) , happiness with the level of communication , and satisfaction with care , as well as a st and ardized measure of anxiety and depression . RESULTS Thirty-eight patients ( 51 % ) showed preference for the intervention . Discussion s with professionals or family and friends about the future increased in the intervention arms , whether r and omized or preference , but happiness with communication was unchanged or worse , and satisfaction with services decreased . Trial participation did not cause significant anxiety or depression and attrition was low . SIGNIFICANCE OF RESULTS A r and omized trial of advance care planning is possible . This study provides new evidence on its acceptability and effectiveness for patients with advanced cancer CONTEXT Latinos experience significant health disparities at the end of life compared with non-Latinos . OBJECTIVES To determine the feasibility of a patient navigator intervention to improve palliative care outcomes for Latino adults with serious illness . METHODS This was a pilot r and omized controlled trial that included 64 Latino adults with life-limiting illness r and omized to an intervention or a control group . All participants received a packet of linguistically matched material s on palliative care . In addition , intervention participants received up to five home visits from the bilingual , bicultural patient navigator . Visits focused on addressing barriers to palliative care through education , activation , and culturally tailored messaging . Outcomes included feasibility and advance care planning rates , documentation of pain management discussion s in the medical record , and hospice utilization . RESULTS Of the 32 patients r and omized to the intervention arm , 81 % had at least one home visit ( range 1 - 5 ) with the patient navigator . Overall , advance care planning was higher in the intervention group ( 47 % [ n = 15 ] vs. 25 % [ n = 8 ] , P = 0.06 ) , and 79 % of intervention participants had a discussion about pain management documented in their medical record vs. 54 % of control patients ( P = 0.05 ) . Hospice enrollment between the two groups ( n = 18 decedents ) was similar ( n = 7 intervention vs. n = 6 control ) ; length of stay in the intervention group was 36.4 ± 51.6 vs. 19.7 ± 33.6 days for control patients ( P = 0.39 ) . CONCLUSION A culturally tailored patient navigator intervention was feasible and suggests improved palliative care outcomes for Latinos facing advanced medical illness , justifying a fully powered r and omized controlled trial BACKGROUND Venous thromboembolism is common in cancer patients and requires anticoagulation with low-molecular-weight heparin ( LMWH ) . Current data recommend LMWH for anticoagulation as far as 6 months , yet guidelines recommend LMWH beyond 6 months in patients who have ongoing or active cancer . This recommendation , based on expert consensus , has not been evaluated in a clinical study . OBJECTIVES ( 1 ) To identify the most clinical ly and cost-effective length of anticoagulation with LMWH in the treatment of cancer-associated thrombosis ( CAT ) ; ( 2 ) to identify practicalities of conducting a full r and omised controlled trial ( RCT ) with regard to recruitment , retention and outcome measurement ; and ( 3 ) to explore the barriers for progressing to a full RCT . DESIGN The Anticoagulation with Low-molecular-weight heparin In the treatment of Cancer-Associated Thrombosis ( ALICAT ) trial is a r and omised , multicentre , feasibility mixed- methods study with three components : ( 1 ) a RCT comparing ongoing LMWH treatment for CAT with cessation of LMWH at 6 months ' treatment ( current licensed practice ) in patients with locally advanced or metastatic cancer , consulted in three clinical setting s ( haematology out patients , oncology out patients and primary care ) ; ( 2 ) a nested qualitative study , including focus groups with clinicians to investigate attitudes for recruiting to the study and identify the challenges of progressing to a full RCT , and semistructured interviews with patients and relatives to explore their attitudes towards participating in the study , and potential barriers and concerns to participation ; and ( 3 ) a UK-wide survey exercise to develop a classification and enumeration system for the CAT models and pathways of care . SETTING A haematology out patients department , an oncology out patients department and primary care . PARTICIPANTS Patients with ongoing active or metastatic cancer who have received 6 months of LMWH for CAT . INTERVENTIONS Ongoing LMWH treatment for CAT versus cessation of LMWH at 6 months ' treatment in patients with locally advanced or metastatic cancer . MAIN OUTCOME MEASURES ( i ) The number of eligible patients over 12 months ; ( ii ) the number of recruited patients over 12 months ( target recruitment rate of 30 % of eligible patients ) ; and ( iii ) the proportion of r and omised participants with recurrent venous thromboembolisms ( VTEs ) during follow-up . RESULTS Following several delays in setting up the RCT component of the study , 5 out of 32 eligible patients consented to be r and omised to the RCT suggesting progression to a full RCT was not feasible . Reasons for non-consenting were primarily based on a fixed preference for continuing or discontinuing treatment after 6 months of anticoagulation , and a fear of r and omisation to their non-preferred option . Views were largely influenced by patients ' initial experience of CAT . Focus groups with clinicians revealed that they would be reticent to recruit to such a study as they had fixed views of best management despite the lack of evidence . Patient pathway modelling suggested that there is a broad heterogeneity of practice with respect to CAT management and co-ordination , with no consensus on which specialty should best manage such cases . CONCLUSIONS The results of the RCT reflect recruitment from the oncology site only and provide no recruitment data from haematology centres . However , it is unlikely that these other sites would have access to more eligible patients . The management of cancer-associated thrombosis beyond 6 months will remain a clinical challenge . As it is unlikely that a prospect i ve study will successfully recruit , other strategies to accrue relevant data are necessary . Currently the LONGHEVA ( Long-term treatment for cancer patients with deep-venous thrombosis or pulmonary embolism ) registry is in development to prospect ively evaluate this important and common clinical scenario . STUDY REGISTRATION This study is registered as clinical trials.gov number NCT01817257 and International St and ard R and omised Controlled Trial Number ( IS RCT N ) 37913976 . FUNDING DETAILS Funding for the ALICAT trial was provided by the Health Technology Assessment programme ( 10/145/01 ) in response to a themed funding call . The study was design ed in accordance with the initial funding brief and feedback from the review process CONTEXT The h and held fan is an inexpensive and safe way to provide facial airflow , which may reduce the sensation of chronic refractory breathlessness , a frequently encountered symptom . OBJECTIVES To test the feasibility of developing an adequately powered , multicenter , multinational r and omized controlled trial comparing the efficacy of a h and held fan and exercise advice with advice alone in increasing activity in people with chronic refractory breathlessness from a variety of medical conditions , measuring recruitment rates ; data quality ; and potential primary outcome measures . METHODS This was a Phase II , multisite , international , parallel , nonblinded , mixed- methods r and omized controlled trial . Participants were central ly r and omized to fan or control . All received breathlessness self-management/exercise advice and were followed up weekly for four weeks . Participants /carers were invited to participate in a semistructured interview at the study 's conclusion . RESULTS Ninety-seven people were screened , 49 r and omized ( mean age 68 years ; 49 % men ) , and 43 completed the study . Site recruitment varied from 0.25 to 3.3/month and screening : r and omization from 1.1:1 to 8.5:1 . There were few missing data except for the Chronic Obstructive Pulmonary Disease Self-Efficacy Scale ( two-thirds of data missing ) . No harms were observed . Three interview themes included 1 ) a fan is a helpful self-management strategy , 2 ) a fan aids recovery , and 3 ) a symptom control trial was welcome . CONCLUSION A definitive , multisite trial to study the use of the h and held fan as part of self-management of chronic refractory breathlessness is feasible . Participants found the fan useful . However , the value of information for changing practice or policy is unlikely to justify the expense of such a trial , given perceived benefits , the minimal costs , and an absence of harms demonstrated in this study Abstract Objective : To evaluate a palliative care home support team based on an inpatient unit . Design : R and omised controlled trial with waiting list . Patients in the study group received the service immediately , those in the control group received it after one month . Main comparison point was at one month . Setting - A city of 300 000 people with a publicly funded home care service and about 200 general practitioners , most of whom provide home care . Main outcome measures : Pain and nausea levels were measured at entry to trial and at one month , as were quality of life for patients and care givers ' health . Results : Because of early deaths , problems with recruitment , and a low compliance rate for completion of question naires , the required sample size was not attained . Conclusion : In design ing evaluations of palliative care services , investigators should be prepared to deal with the following issues : attrition due to early death , opposition to r and omisation by patients and referral sources , ethical problems raised by r and omisation of dying patients , the appropriate timing of comparison points , and difficulties of collecting data from sick or exhausted patients and care givers . Investigators may choose to evaluate a service from various perspectives using different methods : controlled trials , qualitative studies , surveys , and audits . R and omised trials may prove to be impracticable for evaluation of palliative care Objective The aim of the study was to investigate how doctors considered and experienced the concept of equipoise while recruiting patients to r and omized controlled trials ( RCTs ) . Study Design and Setting In-depth interviews with 32 doctors in six publicly funded pragmatic RCTs explored their perceptions of equipoise as they undertook RCT recruitment . The RCTs varied in size , duration , type of complex intervention , and clinical specialties . Interview data were analyzed using qualitative content and thematic analytical methods derived from grounded theory and synthesized across six RCTs . Results All six RCTs suffered from poor recruitment . Doctors wanted to gather robust evidence but experienced considerable discomfort and emotion in relation to their clinical instincts and concerns about patient eligibility and safety . Although they relied on a sense of community equipoise to justify participation , most acknowledged having “ hunches ” about particular treatments and patients , some of which undermined recruitment . Surgeons experienced these issues most intensely . Training and support promoted greater confidence in equipoise and improved engagement and recruitment . Conclusion Recruitment to RCTs is a fragile process and difficult for doctors intellectually and emotionally . Training and support can enable most doctors to become comfortable with key RCT concepts including equipoise , uncertainty , patient eligibility , and r and omization , promoting a more resilient recruitment process in partnership with patients Research ers conducting multi-site studies of interventions for end-of-life symptom management face significant challenges with respect to obtaining an adequate sample and training and retaining on-site study teams . The purpose of this paper is to describe the strategies and responses to these challenges in a multi-site r and omized clinical trial ( RCT ) of the efficacy of massage therapy for decreasing pain among patients with advanced cancer in palliative care/hospice setting s. Over a period of 36 months , we enrolled 380 participants across 15 sites ; 27 % of whom withdrew prior to study completion ( less than the anticipated 30 % rate ) . We saw an average of 68 % turnover amongst study staff . Three key qualities characterized successful on-site study teams : ( 1 ) organizational commitment ; ( 2 ) strong leadership from on-site study coordinators ; and ( 3 ) effective lines of communication between the on-site study coordinators and both their teams and the university-based research team . Issues of recruitment , retention and training should be accounted for in hospice-based research study design and budgeting OBJECTIVE There is a paucity of r and omized controlled trials ( RCTs ) to evaluate models of palliative care . Although interventions vary , all have faced a variety of method ological challenges including adequate recruitment , missing data , and contamination of the control group . We describe the ENABLE II intervention , methods , and sample baseline characteristics to increase intervention and method ological transparency , and to describe our solutions to selected method ological issues . METHODS Half of the participants recruited from our rural U.S. comprehensive cancer center and affiliated clinics were r and omly assigned to a phone-based , nurse-led educational , care coordination palliative care intervention model . Intervention services were provided to half of the participants weekly for the first month and then monthly until death , including bereavement follow-up call to the caregiver . The other half of the participants were assigned to care as usual . Symptoms , quality of life , mood , and functional status were assessed every 3 months until death . RESULTS Baseline data of 279 participants were similar to normative sample s. Solutions to method ological challenges of recruitment , missing data , and " usual care " control group contamination are described . SIGNIFICANCE OF RESULTS It is feasible to overcome many of the method ological challenges to conducting a rigorous palliative care RCT Abstract Objectives To develop a process of advance consent to enable research to be undertaken in patients in the terminal phase . Design Feasibility study of an advance consent process to support a r and omised controlled trial of two antimuscarinic drugs ( hyoscine hydrobromide and glycopyrronium bromide ) in the management of noisy respirations associated with retained secretions ( “ death rattle ” ) . Setting Palliative care wards in a major cancer centre . Participants Patients admitted to a palliative care ward who may develop “ death rattle ” and thus be eligible for r and omisation . Main outcome measures Patient accrual ; acceptability of the consent process . Results Of the 107 patients approached , 58 patients gave advance consent to participate in the study . Of these , 15 patients developed death rattle and were r and omised to receive either hyoscine or glycopyrronium ; 16 patients died elsewhere ; 15 patients died on the palliative care wards but were not r and omised ; 12 patients are still alive . Conclusions Initial assessment suggests that this is a workable consent process allowing research to be undertaken in patients who are unable to give consent at the time of r and omisation . Patient accrual rates to date are lower than needed to recruit adequate numbers in the time allotted to answer the research question Background : Malignant bowel obstruction ( MBO ) is common in patients with advanced cancer . Aim : To perform a phase II study to assess the feasibility of conducting a phase III trial investigating the therapeutic value of gastrografin in MBO . Methods : R and omized double-blinded placebo-controlled feasibility study . Participants received 100 mL of either gastrografin or placebo . Results : Over 8 months , 57 patients were screened and 9 enrolled ( 15.8 % recruitment rate ) . Of the 9 enrolled , 4 received gastrografin ( with 2 completing assessment ) and 5 received placebo ( with 4 completing assessment ) . Conclusions : It is not feasible to conduct a phase III trial using the same study protocol . This study vali date s the use of the phase II feasibility study to assess protocol viability in a palliative population prior to embarking on a larger trial Background The Breathlessness Intervention Service is a novel service for patients with intractable breathlessness regardless of aetiology . It is being evaluated using the Medical Research Council 's framework for the evaluation of complex interventions . This paper describes the feasibility results of Phase II : a single-blinded fast-track pragmatic r and omised controlled trial . Methods A single-blinded fast-track pragmatic r and omised controlled trial was conducted for patients with chronic obstructive pulmonary disease referred to the service . Patients were r and omised to either receive the intervention immediately for an eight-week period , or receive the intervention after an eight-week period on a waiting list during which time they received st and ard care . Outcomes examined included : response rates to the trial ; response rates to the individual question naires and items ; comments relating to the trial functioning made during interviews with patients , carers , referrers and service providers ; and , research er fieldwork notes . Results 16 of the 20 eligible patients agreed to participate in a recruitment visit ( 16/20 ) ; 14 respondents went on to complete a recruitment visit/baseline interview . The majority of those who completed a recruitment visit/baseline interview completed the RCT protocol ( 13/14 ) ; 12 of their carers were recruited and completed the protocol . An unblinding rate of 6/25 respondents ( patients and carers ) was identified . Missing data were minimal and only one patient was lost to follow up . The fast-track trial methodology proved feasible and acceptable . Two of the baseline/ outcome measures proved unsuitable : the WHO performance scale and the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting ( SEIQoL-DW ) . Conclusion This study adds to the evidence that fast-track r and omised controlled trials are feasible and acceptable in evaluations of palliative care interventions for patients with non-malignant conditions . Reasonable response rates and low attrition rates were achieved . Further , with adequate preparation of the research and r and omisation teams , clinicians , and responders , and effective liaison with the clinicians , single-blinding proved possible . Methods were identified to reduce unblinding through careful attention to the type of data collected at unblinded measurement points ; the content of interviews should be carefully considered when design ing blinded-trial protocol s . Trial registration Clinical Trials.gov Objectives Recruiting patients to palliative care r and omised controlled trials ( RCTs ) is particularly challenging . This paper describes and analyses the differing recruitment trajectories for patients with advanced malignant and non-malignant disease to a palliative care RCT , outlining activities undertaken to achieve targets . It will outline the lessons learned in order to inform design and conduct of future studies Background Palliative care has been proposed for progressive non-cancer conditions but there have been few evaluations of service developments . We analysed recruitment , compliance and follow-up data of a fast track ( or wait list control ) r and omised controlled trial of a new palliative care service – a design not previously used to assess palliative care . Methods / Design An innovative palliative care service ( comprising a consultant in palliative medicine , a clinical nurse specialist , an administrator and a psychosocial worker ) was delivered to people severely affected by multiple sclerosis ( MS ) , and their carers , in southeast London . Our design followed the MRC Framework for the Evaluation of Complex Interventions . In phase II we conducted r and omised controlled trial , of immediate referral to the service ( fast-track ) versus a 12-week wait ( st and ard best practice ) . Main outcome measures were : compliance ( the extent the trial protocol was adhered to ) , recruitment ( target 50 patients ) , attrition and missing data rates ; trial outcomes were Palliative Care Outcome Scale and MS Impact Scale . Results 69 patients were referred , 52 entered the trial ( 26 r and omised to each arm ) , 5 refused consent and 12 were excluded from the trial for other reasons , usually illness or urgent needs , achieving our target numbers . 25/26 fast track and 21/26 st and ard best practice patients completed the trial , result ing in 217/225 ( 96 % ) of possible interviews completed , 87 % of which took place in the patient 's home . Main reasons for failure to interview and /or attrition were death or illness . There were three deaths in the st and ard best practice group and one in the fast-track group during the trial . At baseline there were no differences between groups . Missing data for individual question naire items were small ( median 0 , mean 1–5 items out of 56 + items per interview ) , not associated with any patient or carer characteristics or with individual question naires , but were associated with interviewer . Conclusion This is the first time a fast track ( or wait list ) r and omised trial has been reported in palliative care . We found it achieved good recruitment and is a feasible method to evaluate palliative care services when patients are expected to live longer than 3–6 months . Home interviews are needed for a trial of this kind ; interviewers need careful recruitment , training and supervision ; and there should be careful separation from the clinical service of the control patients to prevent accidental contamination . Trial Registration Clinical Trials . Gov Background Recruitment of sufficient participants in an efficient manner is still widely acknowledged to be a major challenge to the mounting and completion of r and omised controlled trials ( RCTs ) . Few recruitment interventions have involved staff undertaking recruitment . This study aim ed i ) to underst and the recruitment process from the perspective of recruiters actively recruiting RCT participants in six pragmatic RCTs , and ii ) to identify opportunities for interventions to improve recruitment . Methods Interviews were undertaken with 72 individuals ( 32 doctors or RCT Chief investigators ( CIs ) ; 40 nurses/other health professionals ) who were actively recruiting participants in six RCTs to explore their experiences of recruitment . The RCTs varied in scale , duration , and clinical context s. Interviews were fully transcribed and analysed using qualitative content and thematic analytic methods derived from grounded theory . For this analysis , data were systematic ally extracted from each RCT and synthesis ed across all six RCTs to produce a detailed and nuanced underst and ing of the recruitment process from the perspectives of the recruiters . Results Recruiters readily identified organisational difficulties , fewer than expected eligible patients , and patients ’ treatment preferences as the key barriers to recruitment . As they described their experiences of recruitment , several previously hidden issues related to their roles as research ers and clinicians emerged , imbued with discomfort and emotion . The synthesis across the RCTs showed that doctors were uncomfortable about aspects of patient eligibility and the effectiveness of interventions , whereas nurses were anxious about approaching potential RCT participants and conflicts between the research and their clinical responsibilities . Recruiters seemed unaware that their views contributed to recruitment difficulties . Their views were not known to RCT CIs . Training and support needs were identified for both groups of staff . Conclusions The synthesis showed that recruitment to these RCTs was a complex and fragile process . Clear obstacles were identified but hidden challenges related to recruiters ’ roles undermined recruitment , unbeknown to RCT CIs . Qualitative research can elicit and identify the hidden challenges . Training and support are then needed for recruiters to become more comfortable with the design and principles of RCTs , so that they can engage more openly with potentially eligible participants and create a more resilient recruitment process Background R and omized controlled trials play a central role in evidence -based practice , but recruitment of participants , and retention of them once in the trial , is challenging . Moreover , there is a dearth of evidence that research teams can use to inform the development of their recruitment and retention strategies . As with other healthcare initiatives , the fairest test of the effectiveness of a recruitment strategy is a trial comparing alternatives , which for recruitment would mean embedding a recruitment trial within an ongoing host trial . Systematic review s indicate that such studies are rare . Embedded trials are largely delivered in an ad hoc way , with interventions almost always developed in isolation and tested in the context of a single host trial , limiting their ability to contribute to a body of evidence with regard to a single recruitment intervention and to research ers working in different context s. Methods / Design The Systematic Techniques for Assisting Recruitment to Trials ( START ) program is funded by the United Kingdom Medical Research Council ( MRC ) Methodology Research Programme to support the routine adoption of embedded trials to test st and ardized recruitment interventions across ongoing host trials . To achieve this aim , the program involves three interrelated work packages : ( 1 ) methodology - to develop guidelines for the design , analysis and reporting of embedded recruitment studies ; ( 2 ) interventions - to develop effective and useful recruitment interventions ; and ( 3 ) implementation - to recruit host trials and test interventions through embedded studies . Discussion Successful completion of the START program will provide a model for a platform for the wider trials community to use to evaluate recruitment interventions or , potentially , other types of intervention linked to trial conduct . It will also increase the evidence base for two types of recruitment intervention . Trial registration The START protocol covers the methodology for embedded trials . Each embedded trial is registered separately or as a sub study of the host trial BACKGROUND Attention to psycho-socio-spiritual needs is considered critical by patients with life-threatening illnesses and their caregivers . Palliative care interventions that address these needs -- particularly spirituality -- are lacking . OBJECTIVE To evaluate the effects of an innovative program to address psycho-socio-spiritual needs in patients with life-threatening illnesses . DESIGN A group intervention entitled Life-Threatening Illness Supportive-Affective Group Experience ( LTI-SAGE ) was developed for reducing patient spiritual , emotional , and death-related distress . SETTING /SUBJECTS African American and Caucasian patients ( n = 69 ) from two hospitals in St. Louis , Missouri , with life-threatening medical conditions ( cancer ; human immunodeficiency virus/acquired immune deficiency syndrome [ HIV/AIDS ] ; geriatric frailty ; liver , kidney , pulmonary , or cardiovascular disease ) were r and omly assigned to intervention or control groups . Intervention patients participated in a maximum of 12 LTI-SAGE groups over a 12-month period . Control patients received st and ard care . MEASUREMENTS Outcome measures were depression symptoms , anxiety , spiritual well-being , and death-related emotional distress . RESULTS After attrition , 51 ( 73.9 % ) patients completed the trial . At the end of the trial , after factoring in compliance , intervention patients had significantly fewer depression symptoms and death-related feelings of meaninglessness and significantly better spiritual well-being than did control patients . CONCLUSIONS The use of the LTI-SAGE model for enhancing the end-of-life illness experience is promising Background : Many health-care providers experience barriers to addressing spiritual needs , such as not having the right vocabulary . The ars moriendi model might be a feasible tool for spiritual history taking in palliative care . Aim : To investigate the effect of a structured spiritual history taking on the spiritual well-being of palliative patients in home care . Design : Cluster r and omized controlled trial , conducted between February and October 2013 . Patients and methods : Registered nurses and general practitioners approached eligible patients with an incurable , life-threatening disease for study participation . Health-care providers allocated to the intervention arm of the study took a spiritual history on the basis of the ars moriendi model . Health-care providers in the control arm provided care as usual . Patient-reported outcomes on spiritual well-being , quality of life , pain , and patient – provider trust were assessed at two points in time . Results : A total of 245 health-care providers participated in the study ( 204 nurses and 41 physicians ) . In all , 49 patient – provider dyads completed the entire study protocol . The median age of the patients was 75 years ( range : 41–95 years ) , and 55 % of the patients were female . There were no significant differences at any point in time in the scores on spiritual well-being , quality of life , pain , or patient – provider trust between the intervention and the control group . Conclusion : This cluster r and omized controlled trial showed no demonstrable effect of spiritual history taking on patient scores for spiritual well-being , quality of life , health-care relationship trust , or pain . Further research is needed to develop instruments that accurately assess the effectiveness of spiritual interventions in palliative care population OBJECTIVE To identify barriers to informed consent in research involving subjects with advanced dementia . DESIGN A r and omized controlled clinical trial of palliative care approaches , compared with usual care , in subjects with advanced dementia who are hospitalized . SETTING A large metropolitan teaching hospital . PARTICIPANTS All patients older than 65 years of age who have advanced dementia and a Functional Assessment Staging score of 6d to 7f and have been admitted to the hospital . MEASUREMENTS Surrogates for all eligible subjects were approached for consent to enroll their family members in the trial . Reasons for refusal to enroll in the study were recorded and categorized as either informed refusal ( i.e. , the surrogate understood the research protocol but declined to give consent for participation ) or as a barrier to informed consent ( i.e. , the surrogates could not participate in the informed consent process or there was no functional surrogate ) . RESULTS Forty-nine percent of 146 eligible subjects could not be enrolled in the study . Only four surrogates refused consent for their family members . Of the remaining 68 patients , 41 eligible subjects ' surrogates could not be engaged in the informed consent process , and 22 subjects did not have a functional surrogate to consent for research . CONCLUSIONS Absence of functional surrogate decision-makers is a major barrier to research and clinical decision-making for hospitalized patients with advanced dementia Enrolling adequate numbers of subjects to research projects that focus on the supportive needs of patients and caregivers is difficult , and this difficulty significantly impedes investigation of this important research area . We report reasons that patients or their informal caregivers declined to participate in one of two r and omized , longitudinal clinical trials testing the Comprehensive Health Enhancement Support System ( CHESS ) , a Web-based information and support scheme for people with advanced cancer and their primary informal caregivers . Patients were asked why they declined participation in these trials ; their responses then were recorded and coded into themes . The leading reasons included factors related to using a computer ( eg , lack of familiarity with using this technology , access to other re sources ) , being attended to by a caregiver ( eg , poor caregiver health , caregiver burden , patient doing well and not needing a caregiver ) , taking part in a study ( eg , survey burden , privacy concerns , wording of the consent form ) , dealing with personal issues ( eg , time commitment , timing of study , feelings of being overwhelmed , and coping styles ) , and lack of interest . By using eligibility criteria that largely parallel those for studies of chemotherapeutic regimens , this research project highlighted reasons why subjects decline participation in clinical trials . This information was specific to supportive care trials ; it may help research ers plan recruitment strategies and enrollment targets To determine the effect of dexamethasone when treating malignant bowel obstruction , 35 patients were r and omized to receive intravenous dexamethasone or a placebo , crossing over to the alternate treatment arm if there had been no resolution of obstruction by day 5 . This was done in two consecutive studies . Patients were stratified according to whether or not they had received specific anticancer therapy within 28 days of study . In trial 1 , 15 out of 22 patients ‘ responded ’ ( resolution of obstruction by day 5 ; 10 on dexamethasone , five on placebo ) . Eleven out of 15 patients were ‘ on treatment ’ . In trial 2 , six out of 13 responded ( three on dexamethasone , three on placebo ) ; three out of six were ‘ on treatment ’ . When both studies are combined , 60 % ( 21/35 ) patients responded ( 13 on dexamethasone , eight on placebo ) . Poor patient accrual terminated both studies . Numbers are too small to allow a combination of studies or formal statistical analysis . We are unable to make any conclusion as to the effectiveness of dexamethasone in the palliation of malignant bowel disease BACKGROUND Method ological challenges such as recruitment problems and participant burden make clinical trials in palliative care difficult . In 2001 - 2004 , two community-based r and omized controlled trials ( RCTs ) of case conferences in palliative care setting s were independently conducted in Australia -- the Queensl and Case Conferences trial ( QCC ) and the Palliative Care Trial ( PCT ) . DESIGN A structured comparative study of the QCC and PCT was conducted , organized by known practical and organizational barriers to clinical trials in palliative care . RESULTS Differences in funding dictated study design s and recruitment success ; PCT had 6 times the budget of QCC . Sample size attainment . Only PCT achieved the sample size goal . QCC focused on reducing attrition through gate-keeping while PCT maximized participation through detailed recruitment strategies and planned for significant attrition . Testing sustainable interventions . QCC achieved a higher percentage of planned case conferences ; the QCC strategy required minimal extra work for clinicians while PCT superimposed conferences on normal work schedules . Minimizing participant burden . Differing strategies of data collection were implemented to reduce participant burden . QCC had short survey instruments . PCT incorporated all data collection into normal clinical nursing encounters . Other . Both studies had acceptable withdrawal rates . Intention-to-treat analyses are planned . Both studies included sub- studies to vali date new outcome measures . CONCLUSIONS Health service interventions in palliative care can be studied using RCTs . Detailed comparative information of strategies , successes and challenges can inform the design of future trials . Key lessons include adequate funding , recruitment focus , sustainable interventions , and mechanisms to minimize participant burden There is little rigorous evidence to underpin clinical guidelines for palliative care . However , research in palliative care is difficult , especially with dying patients . Consent is a major issue , since staff do not wish to invite dying patients to participate in trials . We , therefore , conducted a feasibility study in two units within the North West Wales NHS Trust . We explored two novel approaches to research in palliative care -cluster r and omisation and r and omised consent . All patients admitted to the two units during the study were asked for permission to use their data for research . We allocated the two units , at r and om , to use cluster r and omisation or r and omised consent for three months , and then to crossover to the other design . Of 24 patients dying during cluster-r and omised phases , 13 gave consent on admission to use their data and were , thus , eligible to enter the trial ; however , defined eligibility criteria reduced these to six active participants . Of 29 patients dying during r and omised consent phases , seven gave consent on admission to use their data ; although two were eligible for r and omisation , neither entered the trial . We judge that cluster r and omisation is the more effective design for research with dying patients . Computer simulation , based on data from 1500 dying patients on the Welsh Integrated Care Pathway , shows that crossover cluster trials need much smaller sample s than simple cluster trials . Furthermore , this study has shown that crossover cluster trials are entirely feasible . We recommend a ‘ definitive ’ trial to test the crossover design more widely Research on palliative care presents some unique sampling challenges . The purpose of this paper is to articulate the sampling challenges that palliative care research ers face during phases of study design , conduct , and the reporting of results . Challenges include identifying a target population , avoiding selection bias in the face of clinician and patient denial of serious illness , developing eligibility criteria for a seriously ill population , minimizing high patient refusals due to illness , and accurate reporting of all screened and eligible participants . These challenges are explored within the context of a r and omized clinical trial testing a palliative care intervention . Suggestions for improving scientific rigor in sampling design include 1 ) defining a target population that is consistent with research goals ; 2 ) identifying eligibility criteria that are objective and underst and able to clinicians to yield the desired sample ; and 3 ) reporting results about the target population , sample eligibility /exclusions , and participation using st and ardized criteria Background Untreated pain is common for patients at the end of life . Informal caregivers , often family or friends of patients , are responsible for working with hospice staff to provide pain management . Interdisciplinary team meetings conducted in hospices every 2 weeks provide an opportunity for hospice staff to communicate about pain management with informal caregivers of hospice patients . Purpose We present challenges , solutions , and keys strategies for carrying out a r and omized trial in the hospice setting . Methods We are conducting the Assessing Caregivers for Team Intervention through Video Encounters ( ACTIVE ) study to determine whether regular videoconferencing between hospice patients ’ informal caregivers and the hospice care team alters caregivers ’ perceptions of pain management and patients ’ pain . Participants must be primary caregivers for a hospice patient , at least 18 years of age , capable of providing informed consent , and have access to a computer with a high-speed Internet connection or a telephone . We r and omized caregivers to participate in biweekly team meetings through video or phone conferencing ( intervention ) or to receive usual care from the hospice . All patients receive st and ard hospice care regardless of the group assignment of their informal caregiver . Results As of 1 July 2012 , there have been 1038 new admissions to the participating hospices . Of 391 cases in which no contact was made , 233 patients had died or had life expectancy less than 14 days . Home visits were made to 271 interested and eligible caregivers ; 249 caregivers of 233 patients were r and omly assigned to the usual care or intervention arm . Enrollment is on pace to meet recruitment goals . Lessons Learned Thorough pilot testing of instruments and procedures helped us overcome barriers to conducting research in this vulnerable population . Keys to success included obtaining support from hospice medical directors , including hospice staff in study preparation , minimizing the burden on hospice staff , housing research staff in each participating hospice , using newsletters to enhance communication , developing and maintaining a detailed procedural manual , producing regular data quality reports , developing a secure site to facilitate coding videos for qualitative studies , and holding regular teleconferences with key staff . Limitations Late enrollment of many patients in hospice left little to no time for their caregivers to take part in the intervention . Assisting caregivers of patients with very short life expectancy may require different methods . Conclusions The challenges of conducting r and omized trials with hospice patients and caregivers can be addressed with appropriate study design , well-tested research methods , and proactive monitoring of any issues or problems Dyspnea is a common symptom in palliative care . Despite this , there is uncertainty regarding the role of oxygen to treat the symptom in patients with advanced illness . This r and omized , double-blind , crossover trial examined the effect of oxygen versus air on the relief of dyspnea in patients with advanced cancer . Following the blinded administration of air and oxygen via nasal prongs , 51 patients rated dyspnea and indicated preferences for the blinded treatments . On average , patients improved symptomatically with both air and oxygen , and there were no significant differences between the treatments . The subgroup of 17 hypoxic patients overall did not demonstrate a significant difference between air and oxygen , despite having improved oxygen saturations when administered oxygen . Hypoxia was corrected in 13 of 17 patients using the treatment dose of 4 L/min of oxygen . The experience of dyspnea is a complex , multifactorial phenomenon , with oxygen tension not correlating with the subjective experience . The administration of either air or oxygen via nasal prongs on average confers improvement of the symptom CONTEXT Two million people across the U.K. are living with cancer , often experienced as a long-term condition . They may have unmet needs after active treatment . Rehabilitation aims to address these needs , maximize psychological and physical function , and enable minimum dependency regardless of life expectancy . OBJECTIVES We aim ed to test , in a r and omized controlled trial , the clinical and cost effectiveness of a rehabilitation intervention for patients with advanced , recurrent cancer . METHODS We conducted a two-arm , wait-list control , r and omized trial of a complex rehabilitation intervention delivered by a hospice-based multidisciplinary team vs. usual care for active , progressive , recurrent hematological and breast malignancies , with a follow-up at three months . The primary outcome was the psychological subscale of the Supportive Care Needs Survey ( SCNS ) . Secondary outcomes were other domains of the SCNS , psychological status , continuity of care , quality of life , and re source use . RESULTS Forty-one participants were enrolled and 36 completed the trial . The primary outcome was significantly lower in the intervention arm ( adjusted difference -16.8 , 95 % CI -28.34 to -5.3 ; P = 0.006 ) . The SCNS physical and patient care subscales ( -14.2 , 95 % CI -26.2 to -2.2 ; P = 0.02 and -7.4 , 95 % CI -13.7 to -1.1 ; P = 0.02 , respectively ) and self-reported health state ( 12.8 , 95 % CI 3.2 to 22.4 ; P = 0.01 ) also differed significantly . The incremental cost-effectiveness ratio was £ 19,390 per quality -adjusted life year . CONCLUSION This intervention significantly reduced the unmet needs of cancer survivors and it is likely that it is cost-effective . Despite small numbers , the main effect size was robust . We recommend implementation alongside evaluation in wider clinical setting s and patient population Recent clinical practice guidelines suggest that hospice can be a valuable alternative for patients with advanced heart failure ( HF ) . Unfortunately , there are very few evidence -based nursing interventions to guide symptom management for HF patients in hospice and their caregivers . Nevertheless , conducting clinical research in hospice population s remains fraught with method ological and ethical challenges . Our research team was not naive to the fact that hospice research is difficult . We believed that we had prepared well for a number of contingencies before the beginning of our clinical trial testing the feasibility of delivering a psychosocial intervention to caregivers of patients with HF . Despite the team expertise and well-defined recruitment strategies , the recruitment , both accrual and attrition , remained daunting in this population . The purpose of this article was to report the challenges of recruiting hospice patients with HF and caregivers for our r and omized clinical trial , those we anticipated and those we did not 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 Rigorous clinical research in palliative care is challenging but achievable . Trial participants are likely to have deteriorating performance status , co-morbidities and progressive disease . It is difficult to recruit patients , and attrition unrelated to the intervention being trialled is high . The aim of this paper is to highlight practical considerations from a forum held to discuss these issues by active palliative care clinical research ers . To date , the Australian Palliative Care Clinical Studies Collaborative ( PaCCSC ) has r and omized more than 500 participants across 12 sites in 8 Phase III studies . Insights from the 2010 clinical research forum of the PaCCSC are reported . All active Australian research ers in palliative care were invited to present their current research and address three specific questions : ( 1 ) What has worked well ? ( 2 ) What did n’t work well ? and ( 3 ) How should the research be done differently next time ? Fourteen studies were presented , including six double-blind , r and omized , controlled , multi-site trials run by the PaCCSC . Key recommendations are reported , including guidance on design ; method ologies ; and strategies for maximizing recruitment and retention . These recommendations will help to inform future trial design and conduct in palliative care Oral dryness ( xerostomia ) is a common problem to cancer patients and although there are a number of treatments available few have been studied in the palliative patient by r and omized controlled trials . Thehigh prevalenceof this problem led the research team toconduct a r and omized trialof the effectsof threepotential xerostomia-relieving products on patients presenting with mouth dryness within Holme Tower , Marie Curie Centre . Recruitment into this study commenced in November 1998 following a comprehensive set-up programme that aim ed to inform all staff of the project ’s objectives and methodology . The centre ’s research nurse , who was well known within the unit , was responsible for screening individuals to establish whether they were physically and emotionally capable of a conversation with the research er about the study . Over a 5-month period the research nurse screened 155 patients , but clinical staff , predominantly nurses , granted access to 20 Ð a mere 13 % of cases . In the majority of cases , it was verbalized that the patient was ` too poorly ’ to be approached . Subsequently only four individuals were recruited , with none completing the 3-week project per protocol due to deterioration . Due to the poor level of recruitment achieved , the trial was closed down in March 1999 after the withdrawal of funding by the study ’s sponsors . It was felt that before further rigorous studies could be attempted at the unit , the fundamental question of whether research was indeed feasible in such a setting had to be answered . Thus , a new xerostomia treatment study was introduced that was extremely simple in design ( crossover of two treatments ) and was centred around the aims of raising the profile of research and getting staff involved in all stages of the process . It must be emphasized that this was not intended to be scientific investigation into the relative product efficacies , but a feasibility study into the future of palliative care research at Holme Tower . This simplified trial started in August 1999 and , due to the natural turnover of staff , was conducted by a new research team We report the challenges of the Working to Improve Discussion s About Defibrillator Management trial , our novel , multicenter trial aim ed at improving communication between cardiology clinicians and their patients with advanced heart failure ( HF ) who have implantable cardioverter defibrillators ( ICDs ) . The study objectives are ( 1 ) to increase ICD deactivation conversations , ( 2 ) to increase the number of ICDs deactivated , and ( 3 ) to improve psychological outcomes in bereaved caregivers . The unit of r and omization is the hospital , the intervention is aim ed at HF clinicians , and the patient and caregiver are the units of analysis . Three hospitals were r and omized to usual care and three to intervention . The intervention consists of an interactive educational session , clinician reminders , and individualized feedback . We enroll patients with advanced HF and their caregivers , and then we regularly survey them to evaluate whether the intervention has improved communication between them and their HF providers . We encountered three implementation barriers . First , there were institutional review board concerns at two sites because of the palliative nature of the study . Second , we had difficulty in creating entry criteria that accurately identified an HF population at high risk of dying . Third , we had to adapt our entry criteria to the changing l and scape of ventricular assist devices and cardiac transplant eligibility . Here we present our novel solutions to the difficulties we encountered . Our work has the ability to enhance conduct of future studies focusing on improving care for patients with advanced illness Noisy breathing at the end of life ( noisy breathing ( “ NB ” ) occurs in up to 90 % of people . Interventions have not been systematic ally evaluated . There has been clinical observation coupled with a proposed mechanism of effect that supports a role for octreotide in management of NB . The aim of this phase II study was to assess ten completed participants for the feasibility of an adequately powered phase III study . This r and omized , double-blind , crossover pilot trial recruited participants from an inpatient palliative unit . Participants while well and their proxies simultaneously provided written informed consent . If NB were encountered , people were r and omized to 200 mcg octreotide or 400 mcg hyoscine hydrobromide subcutaneously . If subsequent treatment was needed , the other medication was administered . A five point categorical scale documented the nurses ' assessment of secretions over six hours . Eighty participants were consented of whom 10 ( 3 females , 7 males ; median age 79 , all with advanced cancer ) received medication , five in each arm . There was no difference in the median time to administration of the second medication ( 3 hours ) . Two participants in each arm had a 2 category reduction of intensity after the second medication . Although feasible to consent and study this population in a way that respects autonomy and dignity even in the terminal hours of life , this pilot study suggests reconsideration of the pharmacological interventions ( choice of agents , dosing , timing of dosing and pharmacokinetic profiles ) , st and ardizing of non-pharmacological care ; and ways to measure directly family distress before further r and omized studies for this symptom PURPOSE / OBJECTIVES To report the experience of a group of research ers who have had a year of experience in a clinical trial with homecare hospice patients . SAMPLE 150 hospice patients with cancer and their primary caregivers who were accrued to a National Cancer Institute-funded clinical trial focusing on quality of life . METHODS The investigative team kept careful records of the numbers of patient/caregiver dyads accrued to the study and the reasons for nonaccrual as well as reasons for attrition . Data were analyzed using descriptive statistics . FINDINGS During a nine-month period , the hospice admitted 2,517 patients ; 75 % had cancer and 95 % had caregivers , making them eligible for the study . However , after further screening , only 19 % were eligible for contact and only 5 % finally were accrued to the study . For the 125 patient/caregiver dyads actually accrued to the study , baseline data were obtained on only 50 % and evaluable follow-up data on only 50 % . CONCLUSIONS Accruing patients to clinical trials and retaining them when they are critically ill and near death are extraordinarily difficult tasks . The inability to recruit and retain subjects for clinical trials has implication s for integrity of data , data analysis , success of the project , and the cost of conducting such projects in the future The Patient Care Travelling Record ( PCTR ) is a passport-like health-care summary that , in previous research by the authors , has been found to be a feasible and acceptable tool to convey important clinical information about the palliative care patient . This r and omized controlled trial was conducted to determine the effectiveness and efficiency of this Record in improving patient mood , decreasing uncertainty , improving satisfaction with health care , reducing use of health-care services , and maximizing pain control . Eligible patients were r and omized to receive or not receive the PCTR ( completed by nurse or physician and review ed jointly with the patient ) . As baseline entry into the study and then at 1 and 2 months , patients completed measures on level of certainty , mood states , satisfaction with care , levels of pain , and health-care services utilization . During the 2-year study period , only 20 % ( N = 61 ) of the patients enrolled in a palliative care program in Southern Ontario were eligible for the trial . Of these patients , 18 died , 15 declined to participate , and 7 were emotionally unable to complete the question naires . Thus 21 patients completed the trial . With the exception of those age 65 years and over , the patients using the Record reported decreased levels of uncertainty on follow-up . There was no additional use of health-care services , no differences in mood states , pain relief , or satisfaction with health care . It is significant that 80 % of palliative patients were not eligible because their physical and psychological status rendered them insufficiently stable to participate in a research study . Because of their vulnerable status , these patients may be ideal for the utilization of the Record in clinical care . Although research in this palliative care population is challenging due to difficulties with recruitment and high dropout rates due to death , the PCTR , which was previously shown to be acceptable and feasible , has now been shown to be effective in reducing patient uncertainty , specifically for adults under 65 years . Indications for future research are described Background : Since the 1990s there has been increasing emphasis on ‘ evidence -based medicine ’ . The r and omized controlled trial is widely regarded as the ‘ gold-st and ard ’ study design for evaluating interventions . However , placing too strong an emphasis on a phase III trial , to the neglect of earlier development and piloting work , may result in weaker interventions that are more difficult to evaluate and less likely to be implemented . Aim : To illustrate the benefits and outcomes of qualitative research at the early stages of the research continuum . Setting / Participants : Two cancer studies are evaluated in which the best treatment option is uncertain : ASPECTS ( A Study of Patients ExperienCes of TreatmentS ) and ProtecT ( Prostate Testing for Cancer and Treatment ) . Design : To examine decision-making in relation to palliative chemotherapy for advanced cancer , ASPECTS was a qualitative study involving non-participant observation and recording of oncology consultations . During the ProtecT feasibility study , recruitment interviews were routinely audiotaped and in-depth interviews conducted with men to explore their underst and ing of treatment options and r and omization to trial arms . Results : ASPECTS identified that insufficient information was given to patients about the survival benefits of palliative chemotherapy with implication s for informed consent . ProtecT illustrated the effective use of qualitative research methods to resolve recruitment and r and omization problems for a r and omized controlled trial . Conclusions : These studies illustrate the value of qualitative research , particularly during the earlier phases of the research continuum . Such research may generate hypotheses , strengthen the development and implementation of interventions and enhance their evaluation : all of which are essential to evidence -based medicine Objective : To determine whether topical benzydamine hydrochloride 3 % cream is more effective than placebo in reducing pain related to pressure areas in palliative care patients . Design : R and omized double-blind , placebo-controlled trial . Setting : Three specialist palliative care units in the north of Engl and , with local ethical committee approval for all sites . Subjects : Hospice in- patients with pain related to pressure areas . Interventions : A single application of either benzydamine hydrochloride 3 % cream or placebo cream to the painful pressure area . Main outcome measures : Pain assessed using 100 mm VAS , an 11 point numerical pain score and a five-point pain relief score . Results : There was no statistically significant difference between topical benzydamine hydrochloride 3 % cream and placebo cream in reducing pain related to pressure areas in palliative care patients . Conclusions : This study does not demonstrate a statistically significant difference between the two treatments . However the study does provide reliable information with respect to the use of different pain measurement tools in late-stage palliative patients . It also provides information regarding the baseline characteristics of this group of patients which may be useful in the planning of any future similar studies Patients with advanced dementia often receive poor end-of-life care . We aim ed to design and pilot a palliative care and advance care plan ( ACP ) intervention . Patients had undergone emergency hospital admission and had severe dementia . The intervention consisted of a palliative care patient assessment which informed an ACP discussion with the carer , who was offered the opportunity to write an ACP for the person with dementia . Carer – patient dyads were r and omized to ‘ usual care ’ or the intervention . Carer-related outcome measures included the Kessler Distress Scale , Decision Satisfaction Inventory , Client Satisfaction Question naire and the Euroqol-5D , measured at baseline , six weeks , six months and three months after bereavement . The Satisfaction with End of Life Care in Dementia Scale was completed if the patient died . The 32 patient participants were physically frail and in the advanced stages of dementia : 62 % had pressure damage to the skin , all needed feeding assistance and 95 % were in pain . Nearly 50 % died during the six-month follow-up period . Carers were difficult to recruit during acute admission ; 33 patients and carers entered the study ( 22 intervention arm ; 11 control arm ) . Only seven carers made ACPs . The care planning discussion was well received , but few carers wrote an ACP , despite intensive support from an experienced nurse specialist . Advance care planning is , in theory , a necessary intervention for people with severe dementia ; the reluctance of carers to write plans needs to be explored further End-of-life care must be informed by method ologically rigorous , high- quality research , but well-documented barriers make the conduct of palliative care clinical trials difficult . With careful consideration to study design and procedures , these barriers are surmountable . This paper discusses the approach used in a large scale , r and omised , controlled trial of service-based interventions in a regional palliative care service in South Australia , and the impact of this trial on palliative care research more broadly , the changes to the service in which it was conducted , and on health policy beyond palliative care . The Palliative Care Trial evaluated three interventions in a 2 × 2 × 2 factorial cluster r and omised design : case conferences , general practitioner education , and patient education . Main outcomes were performance status , pain intensity , and re source utilisation . A total of 461 patients were enrolled in the study . Pre- study planning and piloting is crucial , and accurately estimated withdrawal and death rates in the study . Other study design elements that facilitated this research included assessment of three interventions at one time , a dedicated recruitment role , a single clinical triage point , embedding data collection into routine clinical assessment s , and meaningful outcome measures . Recruitment and retention of participants is possible if barriers are systematic ally identified and addressed . This study challenged and developed the research culture within our clinical team and subsequently translated into further research Aromatherapy massage is used in cancer palliative care to improve quality of life but there is little evidence for its effectiveness . A large pragmatic multicentre r and omized controlled trial was set up to examine the effectiveness of aromatherapy in improving psychological distress and quality of life in patients with cancer . This paper examines the challenges encountered in the design and execution of the study . The original design , i ) focused on palliative care patients with advanced disease ; ii ) had both a no-intervention and a treatment control group ( relaxation therapy ) ; and iii ) adopted 90 % power for sample size calculations . A varied measurement strategy was employed . Recruitment proved difficult , referrers were ‘ gate-keeping ’ , patients were often too ill to approach and others declined . The trial was modified to ensure viability . Eligibility was extended to all patients with cancer irrespective of stage , the relaxation group was removed and the power reduced to 80 % . Although it is not generally good practice to change a study design once recruitment has started , the changes were consistent with the original basic study aims and design principles . The data collection phase was successfully completed in July 2002 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 PURPOSE Palliative care is increasingly viewed as a necessary component of cancer care , especially for patients with advanced disease . Rigorous clinical trials are thus needed to build the palliative care evidence base , but clinical research -especially participant recruitment-is difficult . Major barriers include ( 1 ) patient factors , ( 2 ) " gatekeeping , " and ( 3 ) ethical concerns . Here we discuss an approach to overcoming these barriers , using the Palliative Care Trial ( PCT ) as a case study . PATIENTS AND METHODS The PCT was a 2 × 2 × 2 factorial r and omized controlled trial ( RCT ) of different service delivery models to improve pain control in the palliative setting . It used a recruitment protocol that fused evidence -based strategies with principles of " social marketing , " an approach involving the systematic application of marketing techniques . Main components included ( 1 ) an inclusive triage algorithm , ( 2 ) information booklets targeting particular stakeholders , ( 3 ) a specialized recruitment nurse , and ( 4 ) st and ardization of wording across all study communications . RESULTS From an eligible pool of 607 patients , the PCT enrolled 461 patients over 26 months . Twenty percent of patients referred to the palliative care service were enrolled ( 76 % of those eligible after screening ) . Several common barriers were minimized ; among those who declined participation , family disinterest was uncommon ( 5 % ) , as was the perception of burden imposed ( 4 % ) . CONCLUSION Challenges to clinical trial recruitment in palliative care are significant but not insurmountable . A carefully crafted recruitment and retention protocol can be effective . Our experience with design ing and deploying a social-marketing-based protocol shows the benefits of such an approach |
12,983 | 27,581,994 | The results do not show any significant effect of memory rehabilitation on performance in objective memory tests , mood , functional abilities , or quality of life .
AUTHORS ' CONCLUSIONS Participants who received cognitive rehabilitation for memory problems following a stroke reported benefits from the intervention on subjective measures of memory in the short term ( i.e. the first assessment point after the intervention , which was a minimum of four weeks ) .
This effect was not , however , observed in the longer term ( i.e. the second assessment point after the intervention , which was a minimum of three months ) .
There was , therefore , limited evidence to support or refute the effectiveness of memory rehabilitation . | BACKGROUND Memory problems are a common cognitive complaint following stroke and can potentially affect ability to complete functional activities .
Cognitive rehabilitation programmes either attempt to retrain lost or poor memory functions , or teach patients strategies to cope with them .
Some studies have reported positive results of cognitive rehabilitation for memory problems , but the results obtained from previous systematic review s have been less positive and they have reported inconclusive evidence .
This is an up date of a Cochrane review first published in 2000 and most recently up date d in 2007 .
OBJECTIVES To determine whether participants who have received cognitive rehabilitation for memory problems following a stroke have better outcomes than those given no treatment or a placebo control .
The outcomes of interest were subjective and objective assessment s of memory function , functional ability , mood , and quality of life .
We considered the immediate and long-term outcomes of memory rehabilitation . | OBJECTIVES To evaluate a paging system design ed to improve independence in people with memory problems and executive deficits . METHODS After a successful pilot study , a r and omised control trial was conducted involving a crossover design with 143 people aged between 8 and 83 years . All had one or more of the following : memory , planning , attention , or organisation problems . Most had sustained a traumatic head injury or a stroke although a few had developmental learning difficulties or other conditions . The crossover design ensured that some people received a pager after a 2 week baseline whereas others were required to wait for 7 weeks after the baseline before receiving the pager . Participants were assessed at three time periods — namely , at baseline , 7 weeks , and at 14 weeks postbaseline . RESULTS More than 80 % of those who completed the 16 week trial were significantly more successful in carrying out everyday activities ( such as self care , self medication , and keeping appointments ) when using the pager in comparison with the baseline period . For most of these , significant improvement was maintained when they were monitored 7 weeks after returning the pager . CONCLUSIONS This particular paging system significantly reduces everyday failures of memory and planning in people with brain injury Deficits in attention and executive control are some of the most common , debilitating and persistent consequences of brain injuries . Underst and ing neural mechanisms that support clinical ly significant improvements , when they do occur , may help advance treatment development . Intervening via rehabilitation provides an opportunity to probe such mechanisms . Our objective was to identify neural mechanisms that underlie improvements in attention and executive control with rehabilitation training . We tested the hypothesis that intensive training enhances modulatory control of neural processing of perceptual information in patients with acquired brain injuries . Patients ( n=12 ) participated either in st and ardized training design ed to target goal -directed attention regulation , or a comparison condition ( brief education ) . Training result ed in significant improvements on behavioural measures of attention and executive control . Functional magnetic resonance imaging methods adapted for testing the effects of intervention for patients with varied injury pathology were used to index modulatory control of neural processing . Pattern classification was utilized to decode individual functional magnetic resonance imaging data acquired during a visual selective attention task . Results showed that modulation of neural processing in extrastriate cortex was significantly enhanced by attention regulation training . Neural changes in prefrontal cortex , a c and i date mediator for attention regulation , appeared to depend on individual baseline state . These behavioural and neural effects did not occur with the comparison condition . These results suggest that enhanced modulatory control over visual processing and a rebalancing of prefrontal functioning may underlie improvements in attention and executive control Aim : To examine the effects of working memory ( WM ) training in adult patients with stroke . Methods : A r and omized pilot study with a treatment group and a passive control group ; 18 participants ( 12 males ) in a vocational age group ( mean age 54 years ) were r and omized to either the treatment or the control condition . The intervention consisted of computerized training on various WM tasks for five weeks . A neuropsychological test battery and self-rating on cognitive functioning in daily life ( the CFQ ) were administered both before and after the treatment . Results : Statistically significant training effects were found on the non-trainedtests for WM and attention , i.e. , tests that measure related cognitive functions but are not identical to tasks in the training programme ( Span board p < 0.05 ; PASAT p < 0.001 ; Ruff 2&7 p < 0.005 ) . There was a significant decrease in symptoms of cognitive problems as measured by the CFQ ( p < 0.005 ) . Conclusion : More than one year after a stroke , systematic WM training can significantly improve WM and attention Objective : Study short- and long-term transfer effects of a computerized working memory ( WM ) training programme for patients suffering from working memory deficits after acquired brain injury . Research design : A controlled experimental study with a cross-over design . Methods : A consecutive sample of 21 subjects . Mean age 43.2 years , time since injury/illness onset 37 months ( median ) . The subjects were r and omly selected into two groups where one group served as controls . All subjects trained daily for 5 weeks in a computer WM task program . They were followed-up at 4 and 20 weeks after the training . Results : A significant improvement in the trained WM tasks , significant improvements in neuropsychological WM-test results at 4 and 20 weeks after training compared to baseline . Improvement in the subjects ’ rated occupational performance and satisfaction with performance in pre-defined occupational problems . Rated quality -of-life did not change . However , rated overall health increased 20 weeks after training . Conclusions : Structured and intense computerized WM training improves subjects ’ cognitive functioning as measured by neuropsychological WM-dem and ing tests , rated occupational performance , satisfaction with performance and rated overall health . The training probably has an impact on the rehabilitation outcome , returning to work , as well as on daily activities for individuals with verified WM impairments The aim of the study was to compare the fidelity of manualised group memory rehabilitation programmes for participants with neurological disabilities . A sample of 11 neurological patients with memory problems , enrolled in a r and omised controlled trial comparing compensation , restitution and self-help treatments , were observed during group sessions . Time-sampling was used to record the activity of the participants and the content of the discussion at one minute intervals . There was a significant difference between groups in the amount of time the group leader and participants spent talking ( p < .001 ) . Participants in the compensation and restitution groups spent significantly more time in memory rehabilitation discussion than participants in the self-help group ( p < .001 ) . There was also a significant difference between the amount of time spent discussing internal and external memory aids in the compensation and restitution groups ( p < .001 ) . These results support the fidelity of the interventions provided . This study also highlights the usefulness of time-sampling as a method to record the content and activity in rehabilitation groups Cognitive impairment is a frequent complication of stroke . The aim of this study was to evaluate the effectiveness of cognitive training performed early after stroke . Ninety-two patients were r and omly assigned to either the study group ( SG ) or the control group ( CG ) . Cognitive rehabilitation consisted of 16 individual one-hour sessions in which patients performed therapist- guided computer exercises . The patients in the CG performed a sham intervention . After four weeks all the patients were re-evaluated . In the SG , significant improvements ( p<0.05 ) were detected in all neuropsychological measures at the post-training evaluation , while the CG showed mild ( not statistically significant ) improvements on cognitive tests . Between-group analysis revealed statistically significant differences in the domains of memory and visual attention . Cognitive training performed early after stroke seems to be a viable option for improving cognitive outcome in stroke survivors . Further studies should assess whether this may favor their reintegration into everyday life BACKGROUND AND PURPOSE To be useful for clinical research , an outcome measure must be feasible to administer and have sound psychometric attributes , including reliability , validity , and sensitivity to change . This study characterizes the psychometric properties of the Stroke Impact Scale ( SIS ) Version 2.0 . METHODS Version 2.0 of the SIS is a self-report measure that includes 64 items and assesses 8 domains ( strength , h and function , ADL/IADL , mobility , communication , emotion , memory and thinking , and participation ) . Subjects with mild and moderate strokes completed the SIS at 1 month ( n=91 ) , at 3 months ( n=80 ) , and at 6 months after stroke ( n=69 ) . Twenty-five subjects had a replicate administration of the SIS 1 week after the 3-month or 6-month test . We evaluated internal consistency and test-retest reliability . The validity of the SIS domains was examined by comparing the SIS to existing stroke measures and by comparing differences in SIS scores across Rankin scale levels . The mixed model procedure was used to evaluate responsiveness of the SIS domain scores to change . RESULTS Each of the 8 domains met or approached the st and ard of 0.9 alpha-coefficient for comparing the same patients across time . The intraclass correlation coefficients for test-retest reliability of SIS domains ranged from 0.70 to 0.92 , except for the emotion domain ( 0.57 ) . When the domains were compared with established outcome measures , the correlations were moderate to strong ( 0.44 to 0.84 ) . The participation domain was most strongly associated with SF-36 social role function . SIS domain scores discriminated across 4 Rankin levels . SIS domains are responsive to change due to ongoing recovery . Responsiveness to change is affected by stroke severity and time since stroke . CONCLUSIONS This new , stroke-specific outcome measure is reliable , valid , and sensitive to change . We are optimistic about the utility of measure . More studies are required to evaluate the SIS in larger and more heterogeneous population s and to evaluate the feasibility and validity of proxy responses for the most severely impaired patients Background Stroke is one of the most common causes of cognitive impairment . Up to 75 % of stroke survivors may be considered to have cognitive impairment , which severely limit individual autonomy for successful reintegration into family , work and social life . The clinical efficacy of acupuncture with Baihui ( DU20 ) and Shenting ( DU24 ) in stroke and post-stroke cognitive impairment has been previously demonstrated . Computer-assisted cognitive training is part of conventional cognitive rehabilitation and has also shown to be effective in improvement of cognitive function of affected patients . However , the cognitive impairment after stroke is so complexity that one single treatment can not resolve effectively . Besides , the effects of acupuncture and RehaCom cognitive training have not been systematic ally compared , nor has the possibility of a synergistic effect of combination of the two therapeutic modalities been evaluated . Our primary aim of this trial is to evaluate the synergistic effect of acupuncture and RehaCom cognitive training on cognitive dysfunction after stroke . Method / Design A r and omized controlled trial of 2 × 2 factorial design will be conducted in the Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine . A total of 240 patients with cognitive dysfunction after stroke who meet the eligibility criteria will be recruited and r and omized into RehaCom training group , acupuncture group , a combination of both or control group in a 1:1:1:1 ratio . All patients will receive conventional treatment . The interventions will last for 12 weeks ( 30 min per day , Monday to Friday every week ) . Evaluations will be conducted by blinded assessors at baseline and again at 4 , 8 and 12 weeks . Outcome measurements include mini – mental state examination ( MMSE ) , Montreal cognitive assessment s ( MoCA ) , functional independence measure scale ( FIM ) and adverse events . Discussion The results of this trial are expected to clarify the synergistic effect of acupuncture and RehaCom cognitive training on cognitive dysfunction after stroke . Furthermore , to confirm whether combined or alone of acupuncture and RehaCom cognitive training , is more effective than conventional treatment in the management of post-stroke cognitive dysfunction . Trial registration Chinese Clinical Trial Registry : ChiCTR-TRC-13003704 . Registration date : 4 September , 2013 BACKGROUND Rehabilitation of impaired cognitive functions begins to be considered a st and ard component of medical care after acquired brain injury . Indeed , many evidence s support the effectiveness of the two major categories of techniques , i.e. the traditional and computer-assisted ones , which are widely used in cognitive rehabilitative treatment . OBJECTIVE Aim of this study is to evaluate the effects of pc - cognitive training in brain injury patients . METHODS We studied 35 subjects ( r and omly divided into two groups ) , affected by traumatic or vascular brain injury , having attended from January 2010 to December 2012 the Laboratory of Robotic and Cognitive Rehabilitation of IRCCS Neurolesi of Messina . Cognitive impairment was investigated through psychometric battery , administered before ( T0 ) and two months ( T1 ) after the cognitive pc-training , which was performed only by the experimental group , in addition to conventional treatment . Statistical analysis was performed using Wilcoxon test with a p < 0.01 . RESULTS At time T0 , all patients showed language deficits and cognitive alterations in visual attention and memory abilities . After the rehabilitation program we noted a global improvement in both the groups . However , at T1 , the experimental group showed a greater cognitive improvement than the control group , with significant differences in nearly all the neuropsychological tests performed . CONCLUSIONS Our data suggest that cognitive pc-training may be a promising methodology to optimize the rehabilitation outcomes following brain injury Memory problems are common in patients with a range of neurological conditions , but there have been few attempts to provide and evaluate the usefulness of memory training for groups of neurological out patients . We used a waitlist-controlled trial design to assess the effectiveness of a newly created , 6-session intervention , which involved training in the use of compensatory strategies as well as education regarding memory function , neurological damage , sleep and lifestyle factors that have an impact on memory . Fifty-six patients with neurological conditions ( e.g. , stroke , epilepsy ) and memory complaints completed the training and assessment s. Outcomes were evaluated in terms of reported strategy use as well as objective and subjective measures of antero grade and prospect i ve memory . Training result ed in significant improvements on number of strategies used , scores on the Rey Auditory Verbal Learning Test ( total learning and delayed recall ) and self-report on the Comprehensive Assessment of Prospect i ve Memory . Improvements were stable at 3-month follow-up . Better individual outcomes were related to lower baseline memory scores , fewer symptoms of depression and greater self-awareness of memory function . Overall the study provides encouraging results to indicate that patients with neurological conditions such as stroke and epilepsy can show improvements in memory after a relatively short group-based intervention Background and Purpose — Impaired attention contributes to poor stroke outcomes . Attention process training ( APT ) reduces attention deficits after traumatic brain injury . There was no evidence for effectiveness of APT in stroke patients . This trial evaluated effectiveness of APT in improving attention and broader outcomes in stroke survivors 6 months after stroke . Methods — Participants in this prospect i ve , single-blinded , r and omized , clinical trial were 78 incident stroke survivors admitted over 18 months and identified via neuropsychological assessment as having attention deficit . Participants were r and omly allocated to st and ard care plus up to 30 hours of APT or st and ard care alone . Both groups were impaired ( z≤−2.0 ) across measures of attention at baseline , with the exception of Paced Auditory Serial Addition Test , which was below average ( z≤−1.0 ) . Outcome assessment occurred at 5 weeks and 6 months after r and omization . The primary outcome was Integrated Visual Auditory Continuous Performance Test Full-Scale Attention Quotient . Results — APT result ed in a significantly greater ( P<0.01 ) improvement on the primary outcome than st and ard care . Difference in change on the Cognitive Failures Question naire approached significance ( P=0.07 ) . Differences on other measures of attention and broader outcomes were not significant . Conclusion — APT is a viable and effective means of improving attention deficits after incident stroke Primary objective : Navigational skills are fundamental to community travel and , hence , personal independence and are often disrupted in people with cognitive impairments . Navigation devices are being developed that can support community navigation by delivering directional information . Selecting an effective mode to provide route-prompts is a critical design issue . This study evaluated the differential effects on pedestrian route finding using different modes of prompting delivered via a h and held electronic device for travellers with severe cognitive impairments . Research design : A within-subject comparison study was used to evaluate potential differences in route navigation performance when travellers received directions using four different prompt modes : ( 1 ) aerial map image , ( 2 ) point of view map image , ( 3 ) text based instructions/no image and ( 4 ) audio direction/no image . Methods and procedures : Twenty travellers with severe cognitive impairments due to acquired brain injury walked four equivalent routes using four different prompting modes delivered via a wrist-worn navigation device . Navigation scores were computed that captured accuracy and confidence during navigation . Main outcome : Results of the repeated measures Analysis of Variance suggested that participants performed best when given prompts via speech-based audio directions . The majority of the participants also preferred this prompting mode . Findings are interpreted in the context of cognitive re source allocation theory OBJECTIVE To compare a specialized interprofessional team approach to community-based stroke rehabilitation with usual home care for stroke survivors using home care services . METHODS R and omized controlled trial of 101 community-living stroke survivors ( < 18 months post-stroke ) using home care services . Subjects were r and omized to intervention ( n=52 ) or control ( n=49 ) groups . The intervention was a 12-month specialized , evidence -based rehabilitation strategy involving an interprofessional team . The primary outcome was change in health-related quality of life and functioning ( SF-36 ) from baseline to 12 months . Secondary outcomes were number of strokes during the 12-month follow-up , and changes in community reintegration ( RNLI ) , perceived social support ( PRQ85-Part 2 ) , anxiety and depressive symptoms ( Kessler-10 ) , cognitive function ( SPMSQ ) , and costs of use of health services from baseline to 12 months . RESULTS A total of 82 subjects completed the 12-month follow-up . Compared with the usual care group , stroke survivors in the intervention group showed clinical ly important ( although not statistically significant ) greater improvements from baseline in mean SF-36 physical functioning score ( 5.87 , 95 % CI -3.98 to 15.7 ; p=0.24 ) and social functioning score ( 9.03 , CI-7.50 to 25.6 ; p=0.28 ) . The groups did not differ for any of the secondary effectiveness outcomes . There was a higher total per-person costs of use of health services in the intervention group compared to usual home care although the difference was not statistically significant ( p=0.76 ) . CONCLUSIONS A 12-month specialized , interprofessional team is a feasible and acceptable approach to community-based stroke rehabilitation that produced greater improvements in quality of life compared to usual home care . Clinical trials.gov identifier : NCT00463229 Background and purpose . This study aims to determine the long-term effects of a new Memory Self-efficacy ( MSE ) training program for stroke patients on MSE , depression , and quality of life . Methods . In a r and omized controlled trial , patients were allocated to a MSE training or a peer support group . Outcome measures were MSE , depression , and quality of life , measured with the Metamemory-In-Adulthood question naire , Center for Epidemiological Studies –Depression Scale ( CES-D ) , and the Who-Qol Bref question naire , respectively . We used linear mixed models to compare the outcomes of both groups immediately after training , after 6 months , and after 12 months , adjusted for baseline . Results . In total , 153 former in patients from 2 rehabilitation centers were r and omized—77 to the experimental and 76 to the control group . MSE increased significantly more in the experimental group and remained significantly higher than in the control group after 6 and 12 months ( B = 0.42 ; P = .010 ) . Psychological quality of life also increased more in the experimental group but not significantly ( B = 0.09 ; P = .077 ) . However , in the younger subgroup of patients ( < 65 years old ) , psychological quality of life significantly improved in the experimental group compared to the control group and remained significantly higher over time ( B = 0.14 ; P = .030 ) . Other outcome measures were not significantly different between both groups . Conclusions . An MSE training program improved MSE and psychological quality of life in stroke patients aged < 65 years . These effects persisted during 12 months of follow-up Memory complaints are common after stroke , yet there have been very few studies of the outcome of memory rehabilitation in these patients . The present study evaluated the effectiveness of a new manualised , group-based memory training programme . Forty out patients with a single-stroke history and ongoing memory complaints were enrolled . The six-week course involved education and strategy training and was evaluated using a wait-list crossover design , with three assessment s conducted 12 weeks apart . Outcome measures included : tests of antero grade memory ( Rey Auditory Verbal Learning Test : RAVLT ; Complex Figure Test ) and prospect i ve memory ( Royal Prince Alfred Prospect i ve Memory Test ) ; the Comprehensive Assessment of Prospect i ve Memory ( CAPM ) question naire and self-report of number of strategies used . Significant training-related gains were found on RAVLT learning and delayed recall and on CAPM informant report . Lower baseline scores predicted greater gains for several outcome measures . Patients with higher IQ or level of education showed more gains in number of strategies used . Shorter time since onset was related to gains in prospect i ve memory , but no other stroke-related variables influenced outcome . Our study provides evidence that a relatively brief , group-based training intervention can improve memory functioning in chronic stroke patients and clarified some of the baseline factors that influence outcome This study investigated the remediation and assessment of everyday memory impairment in a sample of long-term acquired brain injury ( ABI ) subjects . The Rivermead Behavioural Memory Test ( RBMT ) and subtests of the Wechsler Memory Scale-Revised ( WMS-R ) were selected to measure global memory performance . A memory question naire and a daily memory checklist were developed from a review of existing self-report question naires . The interrelationships among self-report measures and st and ardized psychometric tests of memory were examined and the findings suggest that self-report measures may be used to obtain relatively accurate information about everyday memory performance . A baseline across groups ' design evaluated the relative effectiveness of two different approaches in training subjects to use a diary to compensate for memory problems . There was a Diary Only ( DO ) approach , which emphasized compensation based upon task specific learning , and a Diary and Self-Instructional Training ( DSIT ) approach , which taught compensation using higher cognitive skills of self-awareness and self-regulation . The results obtained show that , during the treatment phase , the DSIT group more consistently made diary entries , reported less memory problems , and made more positive ratings associated with treatment efficacy . The implication s arising from the current study are that : ( 1 ) the choice of memory assessment procedures need to be guided by the patients ' real daily living needs ; and ( 2 ) an approach based upon self-instructional training has greater ecological validity than an approach that focuses on task specific learning . In general , successful assessment and rehabilitation of memory deficits requires a well-established theoretical basis and sound ecological validity The objective of the study was to examine the effectiveness of a customised personal digital assistant ( PDA ) as a cognitive aid for people with acquired brain injury , using a r and omised parallel-group study . The participants were 34 patients with acquired brain injury in a cognitive rehabilitation setting . The experimental group used a customised PDA , while the control group received care-as-usual ( paper- and -pencil aids ) . Measurements were conducted at baseline ( T0 ) , after 8 hours of training ( T1 ) , after 16 hours of training ( T2 ) , and at 5-month follow-up ( T3 ) . The main outcome was the attainment of individualised goals . Both groups showed a significant increase in goal attainment ( GAS ) ( p < .001 ) . There were no significant differences between the groups at T1 or T2 on any of the other outcome measures . It was concluded that the customised PDA was as effective as paper- and -pencil aids , and may therefore serve as a useful alternative when choosing the optimal rehabilitation strategy for a patient Assistive technologies for cognition ( ATC ) provide an effective means to compensate for prospect i ve memory failures among adults with acquired brain injury ( ABI ; de Joode , van Heugten , Verhey , & van Boxtel , 2010 ; Sohlberg et al. , 2007 ) . This study evaluated a novel ATC device , the Television Assisted Prompting ( TAP ) system , which provides audiovisual reminders at scheduled prospect i ve times on a person 's home television . A r and omised , controlled crossover design evaluated task completion for two preferred , two non-preferred , and two structured experimental tasks among 23 adults with ABI between two conditions : TAP prompting or typical ( TYP ) practice , without TAP reminders . Main outcomes showed a significant advantage of prospect i ve memory prompting ( 72 % completion ) over no prompting ( 43 % completion ) and higher task completion with TAP prompting for research er-assigned experimental tasks ( 81 % ) compared to self-selected preferred ( 68 % ) or non-preferred ( 68 % ) tasks . Results are discussed in the context of ATC efficacy to support prospect i ve memory prompting following ABI , with contributions and future directions for continued investigation of customisation of prompts to maximise task completion Neurorehabilitation of poststroke cognitive impairments is an important medical problem . The purpose of the present study was to estimate the efficacy of new methods of restoration of impaired cognitive functions using computer correction programs . 43 poststroke patients aged 57 - 69 , ( male - 23 , female - 20 ) were r and omized into two groups . First group patients have been treated with the st and ard methods and supplementary neuropsychological computer training for 14days , 25 - 35min of duration per day . Control group received st and ard treatment according to Federal and local medical recommendations . Initial and achieved levels of cognitive functioning were estimated with the use of Mini Mental State Examination , Frontal Assessment Battery , the Clock Drawing Test , the Montreal Cognitive Assessment , Schulte 's test , Hospital Anxiety and Depression Scale . We found that including the computer correction programs into the complex protocol of rehabilitation of post-stroke patients confirmed their efficacy in both clinical aspects and the Patient Global Impression Scale . Although the results are encouraging , further studies are required with larger sample s and longer follow-up to identify characteristics of those patients who are most likely to benefit from computer training of cognitive functions Background : Although cognitive impairments are common following stroke , there is considerable uncertainty about the types of interventions that can reduce activity restrictions and improve quality of life . Indeed , a recent project to identify priorities for research into life after stroke determined that the top priority for patients , carers and health professionals was how to improve cognitive impairments . Objective : To provide an overview of the evidence for the effectiveness of cognitive rehabilitation for patients with stroke and to determine the main gaps in the current evidence base . Methods : Evidence was synthesis ed for the six Cochrane review s relating to rehabilitation for post-stroke cognitive impairment and any subsequently published r and omized controlled trials to February 2012 . Results : Data arising from 44 trials involving over 1500 patients was identified . Though there was support for the effectiveness of cognitive rehabilitation for some cognitive impairments , significant gaps were found in the current evidence base . All of the Cochrane review s identified major limitations within the evidence they identified . Conclusions : There is currently insufficient research evidence , or evidence of insufficient quality , to support clear recommendations for clinical practice . Recommendations are made as to the research required to strengthen the evidence base , and so facilitate the delivery of effective interventions to individuals with cognitive impairment after stroke Background and purpose To analyse the prospect of memory training for patients with organic brain damage . Methods Sixty-two patients with memory disorder were assigned to three different groups : a control group ( n=16 ) with low dose memory training , a process oriented memory training group ( POT ) ( n=24 ) and a group ( ST ) who was taught to compensate for memory problems with different strategies ( n=22 ) . Most of the patients had suffered a stroke . Inclusion criteria were medium to weak memory impairment defined by the patients ’ performance in the California Verbal Learning Test . Patients with complete amnesia were excluded . Specific care was taken that the groups did not differ in age , time since illness , duration of rehabilitation effort , verbal and performance IQ , memory and attention performance . The two treatment groups received 20 hours memory training , the low dose memory training control group 7 sessions . Results The treatment groups improved in verbal and prospect i ve memory , but only the group with POT experienced a significant improvement compared with the control group . Training effects were specific , i. e. they affected verbal memory , but were not encapsulated , i. e. generalized to the recall of prose passages and of appointments . The POT group also showed a statistically weak outperformance compared with the ST group and some attentional improvement as well . Conclusion Memory training is effective in patients with organic brain lesion , but only if applied frequently . Comparing the two training high intensity treatments , a POT focus seems to be superior to teaching a set of compensation strategies Background : Previous studies have demonstrated the effectiveness of paging systems in compensating for everyday memory and planning problems after brain injury , including in individuals with traumatic brain injury ( TBI ) . Methods : Here , in addition to further analyses of the TBI data from a previous r and omised control crossover trial , results are reported from a sub-group of 36 participants with brain injury from cerebrovascular accident ( CVA ) . Results : Results indicate that , as with the TBI group , the pager was effective . However , the pattern of results following cessation of treatment differed . At a group level , TBI participants demonstrated maintenance of pager-related benefits , whereas CVA participants ’ performance returned to baseline levels . Comparisons of demographic and neuropsychological characteristics of the groups showed that the CVA group was older , had a shorter interval post-injury , and had poorer executive function than the TBI group . Furthermore , within the TBI group , maintenance was associated with executive functioning , such that executive dysfunction impeded maintenance . This correlation remained after controlling for demographic differences between groups . Conclusions : Together , these findings suggest that executive dysfunction may affect treatment — for example , whether or not temporary use of the pager is sufficient to establish a subsequently self-sustaining routine Abstract Objective : To study if computerized working memory ( WM ) training , in the sub-acute phase after acquired brain injury , in patients with impaired WM , improves WM , cognition and psychological health . Research design : A r and omized study ( n = 47 ) with an intervention group ( IG ) and a control group ( CG ) , mean age 47.7 years . The WAIS-III NI , Digit span , Arithmetic , Letter-Number Sequences ( Working Memory sub-scale ) , Spatial span , the Barrow Neurological Institute Screen for Higher Cerebral Functions ( BNIS ) and the self-rating scales DEX and HADS were administered at baseline and at follow-ups at 6 and 18 weeks . Both groups underwent integrated rehabilitation . The IG also trained with the computerized WM training program , Cogmed QM , which was offered to the CG and followed up after the study completion . Results : Both groups improved after their WM training in Working Memory , BNIS and in Digit span , particularly the reversed section . Both the BNIS and the Digit span differed significantly between the IG and CG due to the greater improvement in the IG after their WM training . Psychological health improved as both groups reported less depressive symptoms and the CG also less anxiety , after the training . Conclusion : Results indicated that computerized WM training can improve working memory , cognition and psychological health Background . Stroke patients with a low memory self-efficacy ( MSE ) report more memory complaints than patients with a high MSE . Objective . The aim of this study was to examine the effect of a memory-training program on MSE in the chronic phase after stroke and to identify which patients benefit most from the MSE training program . Methods . In a r and omized controlled trial , the effectiveness of the MSE training program ( experimental group ) was compared with a peer support program ( control group ) in chronic stroke patients . The primary outcome was MSE , measured using the Metamemory-In-Adulthood Question naire . Secondary outcomes included depression , quality of life , and objective verbal memory capacity . Changes in outcomes over the intervention period were compared between both groups . Demographic and clinical variables were studied as potential predictors of MSE outcome in the experimental group . Results . In total , 153 patients were included : mean age = 58 years ( st and ard deviation [ SD ] = 9.7 ) , 54.9 % male , and mean of 54 months ( SD = 37 ) after stroke . Of these , 77 were assigned to the training and 76 to the control group . Improvement of MSE ( B = 0.40 ; P = .019 ) was significantly greater in the training than in the control group . No significant differences were found for the secondary outcomes . An increase in MSE after training was predicted by a younger age ( B = −0.033 ; P = .006 ) and a better memory capacity ( B = 0.043 ; P = .009 ) , adjusted for baseline MSE . Conclusions . MSE can be improved by the MSE training program for stroke patients . Younger patients and patients with a better memory capacity benefit most from the MSE training program ( Dutch Trial Register : NTR-TC 1656 ) This study , a quasi-experimental , one-group pretest – post-test design , evaluated the effects on cognitive functioning and cardiorespiratory fitness of 8-week interventions ( aerobic exercise alone and aerobic exercise and cognitive training combined ) in patients with chronic stroke and cognitive impairment living in the community ( participants : n=14 , 61.93±9.90 years old , 51.50±38.22 months after stroke , n=7 per intervention group ) . Cognitive functions and cardiorespiratory fitness were evaluated before and after intervention , and at a 3-month follow-up visit ( episodic memory : revised-Hopkins Verbal Learning Test ; working memory : Brown – Peterson paradigm ; attention omission and commission errors : Continuous Performance Test ; cardiorespiratory fitness : peak oxygen uptake during a symptom-limited , grade d exercise test performed on a semirecumbent ergometer ) . Friedman ’s two-way analysis of variance by ranks evaluated differences in score distributions related to time ( for the two groups combined ) . Post-hoc testing was adjusted for multiple comparisons . Compared with before the intervention , there was a significant reduction in attention errors immediately following the intervention ( omission errors : 14.6±21.5 vs. 8±13.9 , P=0.01 ; commission errors : 16.4±6.3 vs. 10.9±7.2 , P=0.04 ) , and in part at follow-up ( omission errors on follow-up : 3.4±4.3 , P=0.03 ; commission errors on follow-up : 13.2±7.6 , P=0.42 ) . These results suggest that attention may improve in chronic stroke survivors with cognitive impairment following short-term training that includes an aerobic component , without a change in cardiorespiratory fitness . R and omized – controlled studies are required to confirm these findings OBJECTIVE The authors compared changes in client performance on three goals poststroke after the Cognitive Orientation to daily Occupational Performance ( CO-OP ) intervention or st and ard occupational therapy ( SOT ) to determine the magnitude and direction of change . METHOD Eight people living in the community following a stroke were r and omly assigned to receive CO-OP ( n = 4 ) or SOT ( n = 4 ) . CO-OP is a 10-session , cognitive-oriented approach to improving performance that uses client-driven cognitive strategies . SOT was therapist driven and combined task-specific and component-based training . Goal performance was measured by the therapist-rated Performance Quality Rating Scale ( PQRS ) and the participant-rated Canadian Occupational Performance Measure ( COPM ) . RESULTS Using Mann-Whitney U test , we found that CO-OP participants showed significantly greater improvement in performance ( PQRS , p = .02 ; COPM Performance , p = .02 ) compared with SOT but no improvement in satisfaction ( COPM Satisfaction , p = .38 ) . CONCLUSION The CO-OP group demonstrated larger performance improvements than the SOT group . Because of the promising results , an investigation using a larger sample is warranted Prospect i ve memory impairment is common following acquired brain injury ( ABI ) and intervention has proved challenging . The current treatment of choice involves using external memory aids as a method of compensation , with those incorporating active reminders proving most successful . In this paper we report findings of an investigation into the effectiveness of a novel external memory aid , Google Calendar . This aid incorporates active reminders and overcomes some of the limitations associated with existing aids . Twelve participants with ABI took part in the study incorporating a r and omised control crossover within-subjects design , consisting of a 5-week baseline phase , followed by two 5-week intervention phases where either Google Calendar or a st and ard diary were used . Participants identified activities to target during the study and a family member monitored their success . Google Calendar was more effective than the diary in enhancing prospect i ve memory performance . It also proved more popular , on account of its active reminders which helped trigger the retrieval of intentions , whilst reducing the need for monitoring . While further research is required to substantiate these initial findings , it is recommended that clinicians familiarise themselves with using Google Calendar , as it appears to offer additional potential in the management of prospect i ve memory deficits following ABI Background and Purpose — Cognitive impairment occurs in ⩽30 % of all stroke survivors . However , effective therapies aim ed at preventing poststroke cognitive decline are lacking . We assessed the efficacy of a multidomain intervention on preventing cognitive decline after stroke . Methods — In this r and omized , observer-blind trial patients were recruited within 3 months after an acute stroke in 5 Austrian neurological centers . Patients were assigned to a 24-month lifestyle-based multidomain intervention or st and ard stroke care . Primary outcomes were the cognitive subscale of the Alzheimer Disease Assessment Scale ( ADAS-cog ) and occurrence of cognitive decline in the composite scores of at least 2 of 5 cognitive domains at 24 months . Results — A total of 101 patients were r and omized into multi-intervention and 101 into st and ard care during June 2010 and November 2012 . Of them , 76 patients in the intervention group and 83 in the control group were included in the final intention-to-treat analysis . At 24 months , 8 of 76 ( 10.5 % ) patients in the intervention group and 10 of 83 ( 12.0 % ) patients in the control group showed cognitive decline corresponding to a relative risk reduction of 0.874 ( 95 % confidence interval , 0.364–2.098 ) . The change in ADAS-cog from baseline to 24 months was not different either ( median 0 [ IQR , −1 to 2 ] in both groups ; P=0.808 ) . Conclusions — This trial found no benefit of 24-month multidomain intervention with focus on improvement in lifestyle and vascular risk factors on the incidence of poststroke cognitive decline in comparison with st and ard stroke care . Studies with a larger sample size are needed . Clinical Trial Registration — URL : http:// clinical trials.gov . Unique identifier : NCT01109836 Background . Cognitive impairments occur frequently after stroke and contribute to significant disability . Strategy training shows promise but has not been examined in the acute phase of recovery . Objective . We conducted a single-blind r and omized pilot study estimating the effect of strategy training , relative to reflective listening ( attention control ) , for reducing disability and executive cognitive impairments . Methods . Thirty participants with acute stroke who were enrolled in inpatient rehabilitation and had cognitive impairments were r and omized to receive strategy training ( n = 15 , 10 sessions as adjunct to usual inpatient rehabilitation ) or reflective listening ( n = 15 , same dose ) . The Functional Independence Measure assessed disability at baseline , rehabilitation discharge , 3 , and 6 months . The Color Word Interference Test of the Delis – Kaplan Executive Function System assessed selected executive cognitive impairments ( inhibition , flexibility ) at baseline , 3 , and 6 months . Results . Changes in Functional Independence Measure scores for the 2 groups over 6 months showed significant effects of group ( F1,27 = 9.25 , P = .005 ) , time ( F3,74 = 96.00 , P < .001 ) , and group * time interactions ( F3,74 = 4.37 , P < .007 ) after controlling for baseline differences in stroke severity ( F1,27 = 6.74 , P = .015 ) . Color Word Interference Inhibition scores showed significant effects of group ( F1,26 = 6.50 , P = .017 ) and time ( F2,34 = 4.74 , P = .015 ) , but the group * time interaction was not significant ( F2,34 = 2.55 , P = .093 ) . Color Word Interference Cognitive Flexibility scores showed significant effects of group ( F1,26 = 23.41 , P < .001 ) , time ( F2,34 = 12.77 , P < .001 ) , and group * time interactions ( F2,34 = 7.83 , P < .002 ) . Interaction effects suggested greater improvements were associated with strategy training . Conclusions . Strategy training shows promise for addressing disability in the first 6 months after stroke . Lessons from this pilot study may inform future clinical trials Objective To investigate the central mechanism of cognitive training in patients with stroke , using resting state ( RS ) functional magnetic resonance imaging ( fMRI ) . Methods Patients with stroke and executive function and memory deficit were r and omized to receive computer-assisted cognitive training ( treatment group ; total 60 h training over 10 weeks ) or no training ( control group ) . All participants received neuropsychological assessment and RS fMRI at baseline and 10 weeks . Results Patients in the treatment group ( n = 16 ) showed increased functional connectivity ( FC ) of the hippocampus with the frontal lobe ( right inferior , right middle , left middle , left inferior and left superior frontal gyrus ) and left parietal lobe at 10 weeks compared with baseline . Patients in the control group ( n = 18 ) showed decreased FC of the left hippocampus – right occipital gyrus , and right hippocampus – right posterior lobe of cerebellum and left superior temporal gyrus . Significant correlations were found between improved neuropsychological scores and increased FC of the hippocampus with the frontal lobe and left parietal lobe in the treatment group only . Conclusions Increased RS FC of the hippocampus with the frontal and parietal lobes may be an important mechanism of cognitive recovery after stroke Objective : To evaluate the effects of community-based rehabilitation therapy on neurological function deficit in stroke patients . Design : Prospect i ve , single-blind , r and omized controlled multicentre trial . Setting : At home , in Shanghai , China . Subjects : A total of 737 stroke patients in the community . Intervention : The rehabilitation group received additional st and ardized community-based rehabilitation therapy at home for five months . Main outcome measures : Patients were evaluated using the Clinical Neurological Function Deficit Scale before intervention and at the end of two and five months . Results : Although both the rehabilitation group and the control group improved over time , the rehabilitation group showed a greater improvement in Clinical Neurological Function Deficit Scale scores . The differences between the groups were significant . After five months , the Clinical Neurological Function Deficit Scale scores of the cerebral infa rct ion rehabilitation group improved by 6.77 ; the haemorrhage rehabilitation group by 7.99 ; the total rehabilitation group by 7.03 . In comparison , the Clinical Neurological Function Deficit Scale scores of the cerebral infa rct ion control group improved by 1.57 ; the haemorrhage control group by 5.34 ; the total control group by 2.43 . This implies a difference in improvement of 5.2 in the cerebral infa rct ion group , 2.65 in the haemorrhage group , and 4.6 in the total group in favour of the rehabilitation group between groups . Conclusion : St and ardized community-based rehabilitation therapy may help stroke patients to improve their neurological function Background Cognitive impairment after stroke is a considerable burden to patients and their caregivers and occurs in one-third of stroke survivors . No strategy to prevent cognitive decline after stroke exists thus far . Established vascular risk factors have been associated with cognitive decline and may be a target for therapeutic interventions in stroke survivors . Aim To test whether intensive multifactorial non-pharmacologic interventions based on lifestyle modification can reduce the risk of cognitive decline in patients who recently suffered ischemic stroke . Methods A r and omized , controlled , multicenter , observer-blind trial was design ed . The reference group obtains stroke care according to st and ard guidelines . The intervention group additionally receives intensive control and motivation for better compliance with prescribed evidence -based medication , regular blood pressure measurements , healthy diet , regular physical activity and cognitive training . Primary outcomes are the rate of cognitive decline at 24 months , assessed by a neuropsychological test battery and the cognitive subscale of the Alzheimer 's Disease Assessment Scale . Results 202 patients ( 29 % women ) , aged 62 ± 9 years , were recruited during 2010 to 2012 . Stroke related impairment at inclusion was low ( mean National Institutes of Health Stroke Scale : 1.9±1.8 , median modified Rankin Scale : 1 ( 0 - 1 ) ) . At baseline , groups did not differ significantly in demographic , clinical or lifestyle characteristics . Conclusion The recruitment was successful and the groups are balanced regarding potential confounding variables . The study will provide essential data about the feasibility and efficacy of lifestyle intervention after stroke in order to develop a new approach to prevent cognitive decline in patients with mild ischemic stroke Objective : The evidence for the effectiveness of memory rehabilitation is inconclusive . The aim was to compare the effectiveness of two group memory rehabilitation programmes with a self-help group control . Design : Single-blind r and omized controlled trial . Participants : Participants with memory problems following traumatic brain injury , stroke or multiple sclerosis were recruited from community setting s. Interventions : Participants were r and omly allocated , in cohorts of four , to compensation or restitution group treatment programmes or a self-help group control . All programmes were manual-based and comprised two individual and ten weekly group sessions . Main measures : Memory functions , mood , and activities of daily living were assessed at baseline and five and seven months after r and omization . Results : There were 72 participants ( mean age 47.7 , SD 10.2 years ; 32 men ) . There was no significant effect of treatment on the Everyday Memory Question naire ( P = 0.97 ) . At seven months the mean scores were comparable ( restitution 36.6 , compensation 41.0 , self-help 44.1 ) . However , there was a significant difference between groups on the Internal Memory Aids Question naire ( P = 0.002 ) . The compensation and restitution groups each used significantly more internal memory aids than the self-help group ( P < 0.01 ) . There were no statistically significant differences between the groups on measures of mood , adjustment and activities of daily living ( P > 0.05 ) . Conclusions : There results show few statistically significant effects of either compensation or restitution memory group treatment as compared with a self-help group control . Further r and omized trials of memory rehabilitation are needed Few brief self-report memory question naires are available , and non has been well vali date d. We design ed a brief question naire , the MAC-Q , to assess age-related memory decline . Validity and reliability of the MAC-Q were assessed in 232 subjects meeting diagnostic criteria for age-associated memory impairment ( AAMI ) . Concurrent validity of the MAC-Q was supported by a significant correlation ( r = .41 , p < .001 ) with a lengthy , well-vali date d memory question naire . Multiple regression analysis indicated that memory test scores were significant predictors of MAC-Q scores . MAC-Q scores were not predicted by Hamilton Depression Scale scores , suggesting that memory complaint in AAMI is not related to affective status . Internal consistency and test-retest reliability of the MAC-Q were satisfactory . Our data support the validity and reliability of the MAC-Q , a new brief memory question naire . The MAC-Q is of particular relevance to the assessment of AAMI , but should also prove useful in any clinical or research setting requiring a brief index of memory complaint PRIMARY OBJECTIVE The present study reports the results of 103 persons with acquired brain injury who were r and omly assigned to one of three 20-session analogy problem-solving skill training groups , namely : online training ( through computer video conferencing with interactive software ) ; computer-assisted training ( through interactive patient-directed software ) ; therapist administered training ( face-to-face therapist guided training activities ) ; and a " no-treatment " control group . RESEARCH DESIGN Pre- and post-test quasi-experimental design . MAIN OUTCOME AND RESULTS Individuals ' problem-solving skills and self-efficacy in all four groups were assessed over a four-week period . Overall , the training methods were found to be effective in improving problem solving skills regardless of the modes of delivery ( except in the case of the control group ) . The continuous " human touch " characteristics of the therapist-administered group showed significant better improvements in self-efficacy in problem-solving . CONCLUSION The statistically significantly improvement in problem solving skills in the online-group suggests that this approach could effectively improve cognitive functions of person with ABI and yield training outcomes comparable to other modes of delivery such as the face-to-face training . The conceptualization and applicability of tele-cognitive rehabilitation , its implication s for persons with ABI , and future studies in this research area are also discussed Purpose . The purpose of this study was to estimate the effect of the Cognitive Orientation to daily Occupational Performance ( CO-OP ) approach compared with usual outpatient rehabilitation on activity and participation in people <3 months poststroke . Methods . An exploratory , single-blind , r and omized controlled trial , with a usual-care control arm , was conducted . Participants referred to 2 stroke rehabilitation outpatient programs were r and omized to receive either usual care or CO-OP . The primary outcome was actual performance of trained and untrained self-selected activities , measured using the Performance Quality Rating Scale ( PQRS ) . Additional outcomes included the Canadian Occupational Performance Measure ( COPM ) , the Stroke Impact Scale Participation Domain , the Community Participation Index , and the Self-Efficacy Gauge . Results . A total of 35 eligible participants were r and omized ; 26 completed the intervention . Post intervention , PQRS change scores demonstrated that CO-OP had a medium effect over usual care on trained self-selected activities ( d = 0.5 ) and a large effect on untrained activities ( d = 1.2 ) . At a 3-month follow-up , PQRS change scores indicated a large effect of CO-OP on both trained ( d = 1.6 ) and untrained activities ( d = 1.1 ) . CO-OP had a small effect on COPM and a medium effect on the Community Participation Index perceived control and on the Self-Efficacy Gauge . Conclusion . CO-OP was associated with a large treatment effect on follow-up performances of self-selected activities and demonstrated transfer to untrained activities . A larger trial is warranted Objective : To evaluate if home-based rehabilitation of in patients improved outcome compared to st and ard care . Design : Interventional , r and omised , safety/efficacy open-label trial . Setting : University hospital stroke unit in collaboration with three municipalities . Subjects : Seventy-one eligible stroke patients ( 41 women ) with focal neurological deficits hospitalised in a stroke unit for more than three days and in need of rehabilitation . Interventions : Thirty-eight patients were r and omised to home-based rehabilitation during hospitalization and for up to four weeks after discharge to replace part of usual treatment and rehabilitation services . Thirty-three control patients received treatment and rehabilitation following usual guidelines for the treatment of stroke patients . Main measures : Ninety days post-stroke the modified Rankin Scale score was the primary endpoint . Other outcome measures were the modified Barthel-100 Index , Motor Assessment Scale , CT-50 Cognitive Test , EuroQol-5D ™ , Body Mass Index and treatment-associated economy . Results : Thirty-one intervention and 30 control patients completed the study . Patients in the intervention group achieved better modified Rankin Scale score ( Intervention median = 2 , IQR = 2 - 3 ; Control median = 3 , IQR = 2–4 ; P=0.04 ) . EuroQol-5D ™ quality of life median scores were improved in intervention patients ( Intervention median = 0.77 , IQR = 0.66–0.79 ; Control median = 0.66 , IQR = 0.56 – 0.72 ; P=0.03 ) . The total amount of home-based training in minutes highly correlated with mRS , Barthel , Motor Assessment Scale and EuroQol-5D ™ scores ( P-values ranging from P<0.00001 to P=0.01 ) . Economical estimations of intervention costs were lower than total costs of st and ard treatment . Conclusion : Early home-based rehabilitation reduced disability and increased quality of life . Compared to st and ard care , home-based stroke rehabilitation was more cost-effective Objective : To determine the effectiveness of personal digital assistant devices on achievement of memory and organization goals in patients with poor memory after acquired brain injury . Design : Assessor blinded r and omized controlled trial . Setting : Specialist brain injury rehabilitation hospital ( in patients and out patients ) . Participants : Adults with acquired brain impairments ( 85 % traumatic brain injury ; aged ≥17 years ) who were assessed as having functional memory impairment on the Rivermead Behavioural Memory Test ( General Memory Index ) . Interventions : Training and support to use a personal digital assistant for eight weeks to compensate for memory failures by an occupational therapist . The control intervention was st and ard rehabilitation , including use of non-electronic memory aids . Main outcome measures : Goal Attainment Scale which assessed achievement of participants ’ daily memory functioning goals and caregiver perception of memory functioning ; and General Frequency of Forgetting subscale of the Memory Functioning Question naire administered at baseline ( pre-r and omization ) and post intervention ( eight weeks later ) . Results : Forty-two participants with memory impairment were recruited . Use of a personal digital assistant led to greater achievement of functional memory goals ( mean difference 1.6 ( 95 % confidence interval ( CI ) 1.0 to 2.2 ) , P = 0.0001 ) and improvement on the General Frequency of Forgetting subscale ( mean difference 12.5 ( 95 % CI 2.0 to 22.9 ) , P = 0.021 ) . Conclusions : Occupational therapy training in the use of a h and held computer improved patients ’ daily memory function more than st and ard rehabilitation To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrollment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials |
12,984 | 22,006,930 | Four fair- to good- quality diagnostic accuracy studies and 4 fair- to good- quality RCTs showed mixed results of cotesting ( HPV plus cytology ) in women aged 30 years or older compared with cytology alone , with no clear advantage over primary HPV screening . | BACKGROUND Screening programs using conventional cytology have successfully reduced cervical cancer , but newer tests might enhance screening .
PURPOSE To systematic ally review the evidence on liquid-based cytology ( LBC ) and high-risk human papillomavirus ( HPV ) screening for U.S. Preventive Services Task Force use in updating its 2003 recommendation . | Background In the HPV FOCAL trial , we will establish the efficacy of hr-HPV DNA testing as a st and -alone screening test followed by liquid based cytology ( LBC ) triage of hr-HPV-positive women compared to LBC followed by hr-HPV triage with ≥ CIN3 as the outcome . Methods / Design HPV-FOCAL is a r and omized , controlled , three-armed study over a four year period conducted in British Columbia . It will recruit 33,000 women aged 25 - 65 through the province 's population based cervical cancer screening program . Control arm : LBC at entry and two years , and combined LBC and hr-HPV at four years among those with initial negative results and hr-HPV triage of ASCUS cases ; Two Year Safety Check arm : hr-HPV at entry and LBC at two years in those with initial negative results with LBC triage of hr-HPV positives ; Four Year Intervention Arm : hr-HPV at entry and combined hr-HPV and LBC at four years among those with initial negative results with LBC triage of hr-HPV positive cases Discussion To date , 6150 participants have a completed sample and epidemiologic question naire . Of the 2019 women enrolled in the control arm , 1908 ( 94.5 % ) were cytology negative . Women aged 25 - 29 had the highest rates of HSIL ( 1.4 % ) . In the safety arm 92.2 % of women were hr-HPV negative , with the highest rate of hr-HPV positivity found in 25 - 29 year old women ( 23.5 % ) . Similar results were obtained in the intervention arm HPV FOCAL is the first r and omized trial in North America to examine hr-HPV testing as the primary screen for cervical cancer within a population -based cervical cancer screening program . Trial Registration International St and ard R and omised Controlled Trial Number Register , IS RCT BACKGROUND To determine whether testing for DNA of oncogenic human papillomaviruses ( HPV ) is superior to the Papanicolaou ( Pap ) test for cervical-cancer screening , we conducted a r and omized trial comparing the two methods . METHODS We compared HPV testing , using an assay approved by the Food and Drug Administration , with conventional Pap testing as a screening method to identify high- grade cervical intraepithelial neoplasia in women ages 30 to 69 years in Montreal and St. John 's , Canada . Women with abnormal Pap test results or a positive HPV test ( at least 1 pg of high-risk HPV DNA per milliliter ) underwent colposcopy and biopsy , as did a r and om sample of women with negative tests . Sensitivity and specificity estimates were corrected for verification bias . RESULTS A total of 10,154 women were r and omly assigned to testing . Both tests were performed on all women in a r and omly assigned sequence at the same session . The sensitivity of HPV testing for cervical intraepithelial neoplasia of grade 2 or 3 was 94.6 % ( 95 % confidence interval [ CI ] , 84.2 to 100 ) , whereas the sensitivity of Pap testing was 55.4 % ( 95 % CI , 33.6 to 77.2 ; P=0.01 ) . The specificity was 94.1 % ( 95 % CI , 93.4 to 94.8 ) for HPV testing and 96.8 % ( 95 % CI , 96.3 to 97.3 ; P<0.001 ) for Pap testing . Performance was unaffected by the sequence of the tests . The sensitivity of both tests used together was 100 % , and the specificity was 92.5 % . Triage procedures for Pap or HPV testing result ed in fewer referrals for colposcopy than did either test alone but were less sensitive . No adverse events were reported . CONCLUSIONS As compared with Pap testing , HPV testing has greater sensitivity for the detection of cervical intraepithelial neoplasia . ( Current Controlled Trials number , IS RCT N57612064 [ controlled-trials.com ] . ) BACKGROUND Although testing for human papillomavirus ( HPV ) has higher sensitivity and lower specificity than cytology alone for detecting cervical intraepithelial neoplasia ( CIN ) , studies comparing conventional and liquid-based cytology have had conflicting results . METHODS In the first phase of a two-phase multicenter r and omized controlled trial , women aged 35 - 60 years in the conventional arm ( n = 16,658 ) were screened using conventional cytology , and women in the experimental arm ( n = 16,706 ) had liquid-based cytology and were tested for high-risk HPV types using the Hybrid Capture 2 assay . Women in the conventional arm were referred to colposcopy with atypical cells of undetermined significance ( ASCUS ) or higher and those in the experimental arm were referred with ASCUS or higher cytology or with a positive ( > or = 1 pg/mL ) HPV test . Sensitivity and positive predictive value ( PPV ) for detection of cervical intraepithelial neoplasia grade 2 or higher ( CIN2 + ) were calculated . RESULTS The screening methods and referral criterion applied in the experimental arm had higher sensitivity than that in the conventional arm ( relative sensitivity = 1.47 ; 95 % confidence interval [ CI ] = 1.03 to 2.09 ) but a lower PPV ( relative PPV = 0.40 ; 95 % CI = 0.23 to 0.66 ) . With HPV testing alone at > or = 1 pg/mL and at > or = 2 pg/mL , the gain in sensitivity compared with the conventional arm remained similar ( relative sensitivity = 1.43 , 95 % CI = 1.00 to 2.04 and relative sensitivity = 1.41 , 95 % CI = 0.98 to 2.01 , respectively ) but PPV progressively improved ( relative PPV = 0.58 , 95 % CI = 0.33 to 0.98 and relative PPV = 0.75 , 95 % CI = 0.45 and 1.27 , respectively ) . Referral based on liquid-based cytology alone did not increase sensitivity compared with conventional cytology ( relative sensitivity = 1.06 ; 95 % CI = 0.72 to 1.55 ) but reduced PPV ( relative PPV = 0.57 ; 95 % CI = 0.39 to 0.82 ) . CONCLUSIONS HPV testing alone was more sensitive than conventional cytology among women 35 - 60 years old . Adding liquid-based cytology improved sensitivity only marginally but increased false-positives . HPV testing using Hybrid Capture 2 with a 2 pg/mL cutoff may be more appropriate than a 1 pg/mL cutoff for primary cervical cancer screening BACKGROUND Primary cervical screening with both human papillomavirus ( HPV ) DNA testing and cytological examination of cervical cells with a Pap test ( cytology ) has been evaluated in r and omized clinical trials . Because the vast majority of women with positive cytology are also HPV DNA positive , screening strategies that use HPV DNA testing as the primary screening test may be more effective . METHODS We used the data base from the intervention arm ( n = 6,257 women ) of a population -based r and omized trial of double screening with cytology and HPV DNA testing to evaluate the efficacy of 11 possible cervical screening strategies that are based on HPV DNA testing alone , cytology alone , and HPV DNA testing combined with cytology among women aged 32 - 38 years . The main outcome measures were sensitivity for detection of cervical intraepithelial neoplasia grade 3 or worse ( CIN3 + ) within 6 months of enrollment or at colposcopy for women with a persistent type-specific HPV infection and the number of screening tests and positive predictive value ( PPV ) for each screening strategy . All statistical tests were two-sided . RESULTS Compared with screening by cytology alone , double testing with cytology and for type-specific HPV persistence result ed in a 35 % ( 95 % confidence interval [ CI ] = 15 % to 60 % ) increase in sensitivity to detect CIN3 + , without a statistically significant reduction in the PPV ( relative PPV = 0.76 , 95 % CI = 0.52 to 1.10 ) , but with more than twice as many screening tests needed . Several strategies that incorporated screening for high-risk HPV subtypes were explored , but they result ed in reduced PPV compared with cytology . Compared with cytology , primary screening with HPV DNA testing followed by cytological triage and repeat HPV DNA testing of HPV DNA-positive women with normal cytology increased the CIN3 + sensitivity by 30 % ( 95 % CI = 9 % to 54 % ) , maintained a high PPV ( relative PPV = 0.87 , 95 % CI = 0.60 to 1.26 ) , and result ed in a mere 12 % increase in the number of screening tests ( from 6,257 to 7,019 tests ) . CONCLUSIONS Primary HPV DNA-based screening with cytology triage and repeat HPV DNA testing of cytology-negative women appears to be the most feasible cervical screening strategy Objective To assess which of three triage strategies for women with borderline abnormal cervical smear results in the best psychosocial outcomes . Design Pragmatic , non-blinded , multicentre , r and omised controlled trial . Setting 18 family planning clinics across Australia , covering both urban and rural areas , between January 2004 and October 2006 . Participants Women aged 16 - 70 years ( n=314 ) who attended routine cervical screening and received a borderline cervical smear . Interventions Patients were r and omly assigned to human papillomavirus ( HPV ) DNA testing ( n=104 ) , a repeat smear test at six months ( n=106 ) , or the patient ’s informed choice of either test supported by a decision aid ( n=104 ) . Psychosocial outcomes were assessed at multiple time points over 12 months by postal question naire . Main outcome measures We assessed health related quality of life ( SF36 mental health subscale ) , cognitive effects ( such as perceived risk of cervical cancer , intrusive thoughts ) , affective outcomes ( general anxiety [ state-trait anxiety inventory ] ) , specific anxiety about an abnormal smear ( cervical screening question naire ) , and behavioural outcomes ( sexual health behaviour and visits to the doctor ) over 12 months of follow-up . Results At two weeks , some psychosocial outcomes were worse for women allocated to HPV testing compared with those in the smear testing group ( SF36 vitality subscale : t=−1.63 , df=131 , P=0.10 ; intrusive thoughts χ2=8.14 , df=1 , P<0.01 ) . Over 12 months , distress about the abnormal smear was lowest in women allocated to HPV testing and highest in the repeat smear testing group ( t=−2.89 , df=135 , P<0.01 ) . Intrusive thoughts were highest in patients allocated to HPV testing ( 25 % , compared with 13 % in the informed choice group ; difference=12 % , 95 % CI −1.1 % to 25.1 % ) . Women in the HPV DNA group and the informed choice group were more satisfied with their care than women allocated to repeat smear testing . Conclusions Although the psychosocial effect was initially worse for women allocated to HPV triage , over the full year of follow-up this intervention was better for women ’s psychosocial health than repeat smear testing . Offering informed choice could have a small advantage for cognitive outcomes , but in view of the additional effort and logistical complexity that this intervention requires , HPV testing alone can be justified for most women . Trial Registration actr.org.au Identifier : BACKGROUND Testing for human papillomavirus ( HPV ) DNA is reportedly more sensitive than cytology for the detection of high- grade cervical intraepithelial neoplasia ( CIN ) . The effectiveness of HPV testing in primary cervical screening was assessed in the ARTISTIC trial , which was done over two screening rounds approximately 3 years apart ( 2001 - 03 and 2004 - 07 ) by comparing liquid-based cytology ( LBC ) combined with HPV testing against LBC alone . METHODS Women aged 20 - 64 years who were undergoing routine screening as part of the English National Health Service Cervical Screening Programme in Greater Manchester were r and omly assigned ( between July , 2001 , and September , 2003 ) in a ratio of 3:1 to either combined LBC and HPV testing in which the results were revealed and acted on , or to combined LBC and HPV testing where the HPV result was concealed from the patient and investigator . The primary outcome was the detection rate of cervical intraepithelial neoplasia grade 3 or worse ( CIN3 + ) in the second screening round , analysed by intention to treat . This trial is registered with the International St and ard R and omised Controlled Trial Number IS RCT N25417821 . FINDINGS There were 24 510 eligible women at entry ( 18 386 in the revealed group , 6124 in the concealed group ) . In the first round of screening 233 women ( 1.27 % ) in the revealed group had CIN3 + , compared with 80 ( 1.31 % ) women in the concealed group ( odds ratio [ OR ] 0.97 , 95 % CI 0.75 - 1.25 ; p>0.2 ) . There was an unexpectedly large drop in the proportion of women with CIN3 + between the first and second rounds of screening in both groups , at 0.25 % ( 29 of 11 676 ) in the revealed group and 0.47 % ( 18 of 3866 women ) in the concealed group ( OR 0.53 , 95 % CI 0.30 - 0.96 ; p=0.042 ) . For both rounds combined , the proportion of women with CIN3 + were 1.51 % ( revealed ) and 1.77 % ( concealed ) ( OR 0.85 , 95 % CI 0.67 - 1.08 ; p>0.2 ) . INTERPRETATION LBC combined with HPV testing result ed in a significantly lower detection rate of CIN3 + in the second round of screening compared with LBC screening alone , but the effect was small . Over the two screening rounds combined , co-testing did not detect a higher rate of CIN3 + or CIN2 + than LBC alone . Potential changes in screening methodology should be assessed over at least two screening rounds . FUNDING National Institute of Health Research Health Technology Assessment Programme Our study directly compares the performance of liquid-based ( LBC ) and conventional cytology for detecting high- grade cervical intraepithelial neoplasia and cancer ( CIN 2 + ) in high-risk , previously unscreened women . As part of a larger r and omized clinical trial assessing the efficacy and safety of a " screen and treat " program for cervical cancer prevention , 5,652 South African women , aged 35 to 65 years , were screened using either ThinPrep or conventional Papanicolaou cytology . The cytology method used ( i.e. , ThinPrep or conventional ) was rotated on a 6-month basis for the duration of the study . Directly following collection of the cytology specimen , all women underwent colposcopy with endocervical curettage and biopsy of all colposcopic abnormalities . Assessment of cytology and histology results was blinded and results were compared using histology-confirmed CIN as the " gold st and ard . " The accuracy of LBC and conventional cytology was statistically equivalent , although the sensitivity of conventional cytology was at least 5 percentage points higher at all cutoff levels . For example , at a cytology cutoff level of low- grade squamous intraepithelial lesion , the sensitivity of LBC was 60.3 % for CIN2 + vs. 69.1 % for conventional cytology and specificity was 94.1 % and 94.5 % , respectively . LBC specimens were significantly less likely to be " satisfactory-but-limited-by " ( 6.5 % vs. 27.9 % ) but significantly more likely to be unsatisfactory ( 2.2 % vs. 0.8 % ) . Thus , in this high-risk population , the sensitivity of LBC is no greater than the sensitivity of conventional cytology . Because of the higher unit cost of LBC , low re source setting s should carefully consider the potential benefits and drawbacks of LBC before adopting this new technology Background : Human papillomavirus ( HPV ) DNA testing is more sensitive than cytology for detection of cervical intraepithelial neoplasia grade 3 and cancer ( ≥CIN3 ) . Adding HPV testing to cytology is recommended for women ≥30 but long-term prospect i ve studies of HPV testing are rare . Methods : Beginning in 1989–1990 , ∼20,000 women in a prepaid health maintenance organization ( median age = 34 ) were followed passively by recommended annual cytology . We tested archived cervicovaginal lavage specimens collected at enrollment , primarily by MY09-MY11 PCR-based methods , for carcinogenic HPV types . We calculated positive and negative predictive values for the entire study period , and Kaplan – Meier estimates of cumulative probability for ≥CIN3 , up to 18 years of follow-up . Results : We observed 15 cases of invasive cervical cancer during the study period , and 189 cases of CIN3 . Predictive values and Kaplan – Meier analyses yielded the same conclusions . In women 30 and older , the reassurance against ≥CIN3 following a single negative HPV test was long-lasting ( cumulative probability = 0.7 % during follow-up ) . In this age group , a single HPV test ( positive vs. negative , hazard ratio of 8.5 , 95 % CI = 4.8–15.1 ) provided greater long-term risk stratification than a single cytologic result ( abnormal vs. normal , HR = 2.9 , 95 % CI = 1.2–6.6 ) . The risk for ≥CIN3 was higher for HPV16 than for the average of the other carcinogenic types ( hazard ratio = 2.7 ) . Conclusion and Impact : The data from this cohort study show the long-term predictive value of HPV testing , particularly in women ≥30 , and a possible role for distinguishing particularly carcinogenic types like HPV16 . Cancer Epidemiol Biomarkers Prev ; 20(7 ) ; 1398–409 . © 2011 AACR BACKGROUND Tests for the DNA of high-risk types of human papillomavirus ( HPV ) have a higher sensitivity for cervical intraepithelial neoplasia grade 3 or worse ( CIN3 + ) than does cytological testing , but the necessity of such testing in cervical screening has been debated . Our aim was to determine whether the effectiveness of cervical screening improves when HPV DNA testing is implemented . METHODS Women aged 29 - 56 years who were participating in the regular cervical screening programme in the Netherl and s were r and omly assigned to combined cytological and HPV DNA testing or to conventional cytological testing only . After 5 years , combined cytological and HPV DNA testing were done in both groups . The primary outcome measure was the number of CIN3 + lesions detected . Analyses were done by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N20781131 . FINDINGS 8575 women in the intervention group and 8580 in the control group were recruited , followed up for sufficient time ( > or = 6.5 years ) , and met eligibility criteria for our analyses . More CIN3 + lesions were detected at baseline in the intervention group than in the control group ( 68/8575 vs 40/8580 , 70 % increase , 95 % CI 15 - 151 ; p=0.007 ) . The number of CIN3 + lesions detected in the subsequent round was lower in the intervention group than in the control group ( 24/8413 vs 54/8456 , 55 % decrease , 95 % CI 28 - 72 ; p=0.001 ) . The number of CIN3 + lesions over the two rounds did not differ between groups . INTERPRETATION The implementation of HPV DNA testing in cervical screening leads to earlier detection of CIN3 + lesions . Earlier detection of such lesions could permit an extension of the screening interval In a study involving 13 842 women and 113 gynaecologists , liquid-based cytology and HPV testing for detecting cervical cancer were compared . A total of 1334 women were found to be positive for one or both tests and were invited for colposcopy with biopsy . A total of 1031 satisfactory biopsies on 1031 women were thereafter collected using a systematic biopsy protocol , which was r and om in the colposcopically normal-appearing cervix or directed in the abnormal one . In all , 502 women with negative tests were also biopsied . A total of 82 histologic high- grade squamous intraepithelial lesion ( HSIL ) were reported in biopsies , all from the group with one or both tests positive . Sensitivity and specificity to detect histologic HSIL were 59 and 97 % for cytology , and 97 and 92 % for HPV . In total , 14 % of review ed negative cytological preparations associated with histologic HSIL contained no morphologically abnormal cells despite a positive HPV test . This suggested a theoretical limit for cytology sensitivity . HPV viral load analysis of the 1143 HPV-positive sample s showed a direct relationship between abnormal Pap test frequency and HPV viral load . Thus , not only does the HPV testing have a greater sensitivity than cytology but the probability of the latter being positive can also be defined as a function of the associated HPV viral load In a prospect i ve cohort study 8466 women attending routine cervical cancer screening were recruited . Colposcopy was performed on women with any degree of atypia on cytology and /or a positive high-risk human papillomavirus (HPV)-DNA test ( HC2 ; Hybrid Capture 2 © ) , and for a r and omly selected sample of 3.4 % women with negative findings on both . Quality control included review s of cytology , histology , colposcopy images and retesting of sample s with polymerase chain reaction . Test diagnostic performances were based on 7908 women who had complete baseline and follow-up results . Routine histology identified 86 women with high- grade cervical intraepithelial neoplasia ( CIN2 + ) , which was confirmed by review histology in only 46 cases . Sensitivity of routine cytology for the detection of CIN2 + was 43.5 % , with a specificity , positive predictive value ( PPV ) , negative predictive value ( NPV ) of 98.0 , 11.4 and 99.7 % , respectively . Sensitivity of the HC2 test for the detection of CIN2 + was 97.8 % , with a specificity , PPV and NPV , of 95.3 , 10.9 and 100 % , respectively . No high- grade neoplasia was detected in the r and omly selected control group . A negative HPV-test result , even in combination with a positive Papanicolaou ( Pap ) result , virtually excluded any risk of underlying high- grade disease , but this was not the case for a negative Pap result . These data show that HPV testing is of value for the detection or exclusion of prevalent CIN in a routine cervical cancer-screening setting and could be used for further risk classification of women for follow-up management CONTEXT Human papillomavirus ( HPV ) DNA testing of women having Papanicolaou ( Pap ) smears showing atypical squamous cells of undetermined significance ( ASCUS ) has clinical usefulness . Whether HPV DNA testing alone is useful in primary screening remains to be determined . OBJECTIVE To determine the accuracy of HPV DNA testing for detecting cervical intraepithelial neoplasia ( CIN ) grade 3 or cancer ( the criterion st and ard ) . DESIGN , SETTING , AND PARTICIPANTS Between December 1997 and October 2000 , 4075 women who attended Planned Parenthood clinics in Washington State were screened simultaneously using thin-layer Pap and HPV DNA testing by a polymerase chain reaction (PCR)-based method and by a liquid-based RNA-DNA hybridization capture with signal amplification assay ( signal amplification ) . Women who were positive for high-risk HPV types , or had Pap results of ASCUS or higher , were considered to have positive screening test results and were referred for colposcopy and biopsy . Additionally , a r and om sample of women with negative screening test results was referred for colposcopy . Based on individual and combined thin-layer Pap , HPV PCR , and HPV signal amplification test results from the screening and the colposcopy visits , 7 colposcopy triage strategies were defined and evaluated . MAIN OUTCOME MEASURE Sensitivity and specificity for detecting cervical lesions grade d CIN 3 or higher for each of the 7 triage strategies . RESULTS The estimated prevalence of CIN 3 or higher was 3.2 % . The sensitivity ( 95 % confidence interval ) of thin-layer Pap ( with a result of > or = ASCUS ) for identifying women with CIN 3 or higher was only 61.3 % ( 48.5%-70.9 % ) compared with 88.2 % ( 78.9%-93.8 % ) for HPV testing by PCR and 90.8 % ( 83.1%-95.8 % ) by signal amplification . Differences in specificities were also observed : 82.4 % ( 81.8%-83.1 % ) for thin-layer Pap ( with a result of > or = ASCUS ) , 78.8 % ( 77.9%-79.7 % ) for PCR , and 72.6 % ( 69.4%-75.0 % ) for signal amplification . Compared with referral for colposcopy of all women with ASCUS or higher , signal amplification testing of women with ASCUS and referral of those with a positive result was about as sensitive ( 61.3 % vs 60.3 % , respectively ) and significantly more specific ( 82.4 % vs 88.9 % , respectively ) . The strategy requiring repeat positive PCR tests on 2 visits had a sensitivity of 84.2 % ( 75.3%-91.0 % ) and a specificity of 86.2 % ( 85.1%-87.3 % ) . All tests were more specific and less sensitive in older ( > or = 30 years ) vs younger women . CONCLUSIONS Testing for HPV has higher sensitivity but lower specificity than thin-layer Pap screening . In some setting s , particularly where screening intervals are long or haphazard , screening for HPV DNA may be a reasonable alternative to cytology-based screening of reproductive-age women The purpose of the study was to assess the psychosocial impact of human papillomavirus ( HPV ) testing as an adjunct to cytology in routine primary cervical screening . A controlled study of the psychosocial impact of HPV testing within a r and omized trial of HPV testing to assess its efficacy in cervical screening was carried out . The trial provides a r and omized setting of revealed HPV results versus concealed results permitting valid comparisons for assessing true psychosocial impact . The setting comprised a large number of general practice s in primary care . Women aged 20–64 years who underwent routine cervical screening participated in the study . The intervention was a revealed high-risk HPV test result in addition to cervical cytology . The main outcome was measured using General Health Question naire ( GHQ-28 ) , Spielberger State – Trait Anxiety Inventory , and Sexual Rating Scale ( SRS ) . Among women with either mildly abnormal or normal cytology , receiving an HPV(+ ve ) result did not impact significantly on GHQ caseness and mean scores or on Spielberger State and Trait scores when compared with women in whom the HPV(+ ve ) test result was concealed . Among women with normal cytology , receiving an HPV(+ ve ) result was associated with a reduction in the Sexual Rating Scale compared with similar women whose HPV(+ ve ) result was concealed . HPV testing does not add significant psychologic distress when combined with cytology in routine primary cervical screening BACKGROUND Human papillomavirus ( HPV ) DNA testing has shown higher sensitivity than cytology for detecting cervical lesions , but it is uncertain whether the higher sensitivity is dependent on the age of the woman being screened . We compared the age-specific performance of primary HPV DNA screening with that of conventional cytology screening in the setting of an organized population -based cervical cancer screening program in Finl and . METHODS From January 1 , 2003 , to December 31 , 2005 , r and omized invitations were sent to women aged 25 - 65 years for routine cervical cancer screening by primary high-risk HPV DNA testing ( n = 54 207 ) with a Hybrid Capture 2 assay followed by cytology triage for women who were HPV DNA positive or by conventional cytology screening ( n = 54 218 ) . In both screening arms , cytology results of low- grade squamous intraepithelial lesion or worse triggered a referral for colposcopy . Relative rates ( RRs ) of detection to assess test sensitivity , specificity , and positive predictive values ( PPVs ) with 95 % confidence intervals ( CIs ) were calculated for the histological endpoints of cervical intraepithelial neoplasia ( CIN ) grade 1 or higher ( CIN 1 + ) , CIN grade 2 or higher ( CIN 2 + ) , and CIN grade 3 or higher ( CIN 3 + ) . All statistical tests were two-sided . RESULTS The overall frequency of colposcopy referrals was 1.2 % in both screening arms . Women younger than 35 years were referred more often in the HPV DNA screening vs the conventional screening arm ( RR = 1.27 , 95 % CI = 1.01 to 1.60 ) . The prevalence of histologically confirmed CIN or cancer was 0.59 % in the HPV DNA screening arm vs 0.43 % in the conventional screening arm . The relative rates of detection for CIN 1 , CIN 2 , and CIN 3 + for HPV DNA screening with cytology triage vs conventional screening were 1.44 ( 95 % CI = 0.99 to 2.10 ) , 1.39 ( 95 % CI = 1.03 to 1.88 ) , and 1.22 ( 95 % CI = 0.78 to 1.92 ) , respectively . The specificity of the HPV DNA test with cytology triage was equal to that of conventional screening for all age groups ( 99.2 % vs 99.1 % for CIN 2 + , P = .13 ) . Among women aged 35 years or older , the HPV DNA test with cytology triage tended to have higher specificity than conventional screening . The PPVs for HPV DNA screening with cytology triage were consistently higher than those for conventional screening . In both screening arms , the test specificities increased with increasing age of the women being screening , whereas the highest PPVs were observed among the youngest women being screened . Overall , 7.2 % of women in the HPV DNA screening arm vs 6.6 % of women in the conventional screening arm were recommended for intensified follow-up , and the percentages were highest among 25- to 29-year-olds ( 21.9 % vs 10.0 % , respectively ) . CONCLUSIONS Primary HPV DNA screening with cytology triage is more sensitive than conventional screening . Among women aged 35 years or older , primary HPV DNA screening with cytology triage is also more specific than conventional screening and decreases colposcopy referrals and follow-up tests OBJECTIVE To compare the accuracy of conventional cytology with liquid based cytology for primary screening of cervical cancer . DESIGN R and omised controlled trial . SETTING Nine screening programmes in Italy . PARTICIPANTS Women aged 25 - 60 attending for a new screening round : 22 466 were assigned to the conventional arm and 22 708 were assigned to the experimental arm . INTERVENTIONS Conventional cytology compared with liquid based cytology and testing for human papillomavirus . MAIN OUTCOME MEASURE Relative sensitivity for cervical intraepithelial neoplasia of grade 2 or more at blindly review ed histology , with atypical cells of undetermined significance or more severe cytology considered a positive result . RESULTS In an intention to screen analysis liquid based cytology showed no significant increase in sensitivity for cervical intraepithelial neoplasia of grade 2 or more ( relative sensitivity 1.17 , 95 % confidence interval 0.87 to 1.56 ) whereas the positive predictive value was reduced ( relative positive predictive value v conventional cytology 0.58 , 0.44 to 0.77 ) . Liquid based cytology detected more lesions of grade 1 or more ( relative sensitivity 1.68 , 1.40 to 2.02 ) , with a larger increase among women aged 25 - 34 ( P for heterogeneity 0.0006 ) , but did not detect more lesions of grade 3 or more ( relative sensitivity 0.84 , 0.56 to 1.25 ) . Results were similar when only low grade intraepithelial lesions or more severe cytology were considered a positive result . No evidence was found of heterogeneity between centres or of improvement with increasing time from start of the study . The relative frequency of women with at least one unsatisfactory result was lower with liquid based cytology ( 0.62 , 0.56 to 0.69 ) . CONCLUSION Liquid based cytology showed no statistically significant difference in sensitivity to conventional cytology for detection of cervical intraepithelial neoplasia of grade 2 or more . More positive results were found , however , leading to a lower positive predictive value . A large reduction in unsatisfactory smears was evident . TRIAL REGISTRATION Current Controlled Trials IS RCT N81678807 [ controlled-trials.com ] Objective To assess the performance and impact of primary human papillomavirus ( HPV ) DNA screening with cytology triage compared with conventional cytology on cervical cancer and severe pre-cancerous lesions . Design R and omised trial . Setting Population based screening programme for cervical cancer in southern Finl and in 2003 - 5 . Participants 58 076 women , aged 30 - 60 , invited to the routine population based screening programme for cervical cancer . Interventions Primary HPV DNA test ( hybrid capture II ) with cytology triage if the result was positive or conventional cytological screening ( reference ) . Main outcome measures Rate of cervical cancer , cervical intraepithelial neoplasia ( CIN ) grade III , and adenocarcinoma in situ ( as a composite outcome referred to as CIN III+ ) during 2003 - 7 through record linkage between files from the screening registry and the national cancer registry . Results In the HPV and conventional arms there were 95 600 and 95 700 woman years of follow-up and 76 and 53 cases of CIN III+ , respectively ( of which six and eight were cervical cancers ) . The relative rate of CIN III+ in the HPV arm versus the conventional arm was 1.44 ( 95 % confidence interval 1.01 to 2.05 ) among all women invited for screening and 1.77 ( 1.16 to 2.74 ) among those who attended . Among women with a normal or negative test result , the relative rate of subsequent CIN III+ was 0.28 ( 0.04 to 1.17 ) . The rate of cervical cancer between arms was 0.75 ( 0.25 to 2.16 ) among women invited for screening and 1.98 ( 0.52 to 9.38 ) among those who attended . Conclusions When incorporated into a well established organised screening programme , primary HPV screening with cytology triage was more sensitive than conventional cytology in detecting CIN III+ lesions . The number of cases of cervical cancer was small , but considering the high probability of progression of CIN III the findings are of importance regarding cancer prevention . Trial registration Current Controlled Trials IS RCT N23885553 BACKGROUND Human papillomavirus ( HPV ) testing is known to be more sensitive , but less specific than cytology for detecting cervical intraepithelial neoplasia ( CIN ) . We assessed the efficacy of cervical-cancer screening policies that are based on HPV testing . METHODS Between March , 2004 , and December , 2004 , in two separate recruitment phases , women aged 25 - 60 years were r and omly assigned to conventional cytology or to HPV testing in combination with liquid-based cytology ( first phase ) or alone ( second phase ) . R and omisation was done by computer in two screening centres and by sequential opening of numbered sealed envelopes in the remaining seven centres . During phase one , women who were HPV-positive and aged 35 - 60 years were referred to colposcopy , whereas women aged 25 - 34 years were referred to colposcopy only if cytology was also abnormal or HPV testing was persistently positive . During phase two , women in the HPV group were referred for colposcopy if the HPV test was positive . Two rounds of screening occurred in each phase , and all women had cytology testing only at the second round . The primary endpoint was the detection of grade 2 and 3 CIN , and of invasive cervical cancers during the first and second screening rounds . Analysis was done by intention to screen . This trial is registered , number IS RCT N81678807 . FINDINGS In total for both phases , 47,001 women were r and omly assigned to the cytology group and 47,369 to HPV testing . 33,851 women from the cytology group and 32,998 from the HPV-testing group had a second round of screening . We also retrieved the histological diagnoses from screening done elsewhere . The detection of invasive cervical cancers was similar for the two groups in the first round of screening ( nine in the cytology group vs seven in the HPV group , p=0.62 ) ; no cases were detected in the HPV group during round two , compared with nine in the cytology group ( p=0.004 ) . Overall , in the two rounds of screening , 18 invasive cancers were detected in the cytology group versus seven in the HPV group ( p=0.028 ) . Among women aged 35 - 60 years , at round one the relative detection ( HPV vs cytology ) was 2.00 ( 95 % CI 1.44 - 2.77 ) for CIN2 , 2.08 ( 1.47 - 2.95 ) for CIN3 , and 2.03 ( 1.60 - 2.57 ) for CIN2 and 3 together . At round two the relative detection was 0.54 ( 0.23 - 1.28 ) for CIN2 , 0.48 ( 0.21 - 1.11 ) for CIN3 , and 0.51 ( 0.28 - 0.93 ) for CIN2 and 3 together . Among women aged 25 - 34 years , there was significant heterogeneity between phases in the relative detection of CIN3 . At round one the relative detection was 0.93 ( 0.52 - 1.64 ) in phase one and 3.91 ( 2.02 - 7.57 ) in phase two . At round two the relative detection was 1.34 ( 0.46 - 3.84 ) in phase one and 0.20 ( 0.04 - 0.93 ) in phase two . Pooling both phases , the detection ratio of CIN2 for women aged 25 - 34 years was 4.09 ( 2.24 - 7.48 ) at round one and 0.64 ( 0.23 - 1.27 ) at round two . INTERPRETATION HPV-based screening is more effective than cytology in preventing invasive cervical cancer , by detecting persistent high- grade lesions earlier and providing a longer low-risk period . However , in younger women , HPV screening leads to over-diagnosis of regressive CIN2 . FUNDING European Union , Italian Ministry of Health , Regional Health Administrations of Piemonte , Tuscany , Veneto and Emilia-Romagna , and Public Health Agency of Lazio We evaluated the overall agreement between colposcopically directed biopsies and the definitive excisional specimens within the context of three clinical trials . A total of 737 women aged 16 - 45 who had a cervical biopsy taken within 6 months before their definitive therapy were included . Per- protocol , colposcopists were to also obtain a representative cervical biopsy immediately before definitive therapy . Using adjudicated histological diagnoses , the initial biopsies and the same day biopsies were correlated with the surgically excised specimens . The overall agreement between the biopsies taken within 6 months of definitive therapy , and the definitive therapy diagnoses was 42 % ( weighted kappa = 0.34 ) ( 95 % CI : 0.29 - 0.39 ) . The overall underestimation of cervical intraepithelial neoplasia grade 2/3 or adenocarcinoma in situ ( CIN2 - 3/AIS ) and CIN3/AIS was 26 and 42 % , respectively . When allowing for one degree of variance in the correlation , the overall agreement was 92 % for CIN2 - 3/AIS . The overall agreement between the same day biopsy and definitive therapy specimen was 56 % ( weighted kappa = 0.41 ) ( 95 % CI : 0.36 - 0.47 ) , and the underestimation of CIN2 - 3/AIS was 57 % . There were significant associations in the agreement between biopsies and excisional specimen diagnoses when patients were stratified by age , number of biopsies , lesion size , presence of human papillomavirus (HPV)16/18 and region . Of 178 diagnostic endocervical curettages performed , 14 ( 7.9 % ) found any HPV disease . Colposcopic accuracy improved when CIN2 and CIN3/AIS were grouped as a single predictive measure of high- grade disease . Colposcopy functioned well when allowed a one-degree difference between the biopsy and the surgical histologic interpretations , as done in clinical practice . Taking more than one biopsy improved colposcopic accuracy and could improve patient management The purpose was to evaluate alternative cytological screening methods in population -based screening for cervical cancer up to cancer incidence and mortality outcome . Automation-assisted screening was compared to conventional cytological screening in a r and omized design . The study was based on follow-up of 503,391 women invited in the Finnish cervical cancer screening program during 1999 - 2003 . The endpoints were incident cervical cancer , severe intraepithelial neoplasia and deaths from cervical cancer . One third of the women had been r and omly allocated to automation-assisted screening and two thirds to conventional cytology . Information on cervical cancer and severe neoplasia were obtained through 1999 - 2007 from a linkage between screening and cancer registry files . There were altogether 3.2 million woman-years at risk , and the average follow-up time was 6.3 years . There was no difference in the risk of cervical cancer between the automation-assisted and conventional screening methods ; the relative risk ( RR ) of cervical cancer between the study and control arm was 1.00 ( 95 % confidence interval [ CI ] = 0.76 - 1.29 ) among all invited and 1.08 ( 95 % CI = 0.76 - 1.51 ) among women who were test negative at entry . Comparing women who were test negative with nonscreened , RR of cervical cancer incidence was 0.26 , 95 % CI = 0.19 - 0.36 and of mortality 0.24 ( 0.13 - 0.43 ) . Both methods were valid for screening . Because cervical cancer is rare in our country , we can not rule out small differences between methods . Evidence on alternative methods for cervical cancer screening is increasing and it is thus feasible to evaluate new methods in large-scale population -based screening programs up to cancer outcome Objective : We sought to evaluate the performance of the human papillomavirus high-risk DNA test in patients 30 years and older . Material s and Methods : Screening ( n = 835 ) and diagnosis ( n = 518 ) groups were defined based on prior Papanicolaou smear results as part of a clinical trial for cervical cancer detection . We compared the Hybrid Capture II ( HCII ) test result with the worst histologic report . We used cervical intraepithelial neoplasia ( CIN ) 2/3 or worse as the reference of disease . We calculated sensitivities , specificities , positive and negative likelihood ratios ( LR+ and LR− ) , receiver operating characteristic ( ROC ) curves , and areas under the ROC curves for the HCII test . We also considered alternative strategies , including Papanicolaou smear , a combination of Papanicolaou smear and the HCII test , a sequence of Papanicolaou smear followed by the HCII test , and a sequence of the HCII test followed by Papanicolaou smear . Results : For the screening group , the sensitivity was 0.69 and the specificity was 0.93 ; the area under the ROC curve was 0.81 . The LR+ and LR− were 10.24 and 0.34 , respectively . For the diagnosis group , the sensitivity was 0.88 and the specificity was 0.78 ; the area under the ROC curve was 0.83 . The LR+ and LR− were 4.06 and 0.14 , respectively . Sequential testing showed little or no improvement over the combination testing . Conclusions : The HCII test in the screening group had a greater LR+ for the detection of CIN 2/3 or worse . HCII testing may be an additional screening tool for cervical cancer in women 30 years and older . ( Cancer Epidemiol Biomarkers Prev 2008;17(10):2865–71 Diagnostic tests are used to confirm , exclude , classify , or monitor disease to guide treatment . Their clinical value depends on whether the information they provide leads to improved patient outcomes ; this can be assessed by r and omized trials that compare patient outcomes from the new diagnostic test versus the old test strategy . However , r and omized trials of test- and -treatment strategies are not routinely performed . They are not required for marketing approval , and they are not always feasible because they require large sample sizes . As a result , new diagnostic tests frequently enter clinical practice without evidence of improved patient outcomes . Studies of diagnostic test accuracy can show how well diagnostic strategies that include a new test identify the presence or absence of disease compared with an old test strategy by comparing each with the results of a reference st and ard test . However , if clinicians use only information about test accuracy to decide whether to adopt a new diagnostic test , they sometimes may harm patients ( for example , if subsequent treatments are unsafe or ineffective ) . It is therefore worthwhile to investigate how best to decide if clinicians can rely on evidence about test accuracy or if they need to wait for patient outcome results from r and omized trials . Fryback and Thornbury ( 1 ) described a hierarchy of 6 levels of evidence for the assessment of a diagnostic test : 1 ) the technical quality of test information ; 2 ) diagnostic accuracy ; 3 ) change in the referring physician 's diagnostic thinking ; 4 ) change in the patient management plan ; 5 ) change in patient outcomes ; and 6 ) societal costs and benefits . This framework does not provide guidelines about if and when lower levels of evidence are adequate to assess a test and always requires r and omized trials for conclusions about improved patient outcomes . Some research ers have suggested that accuracy studies alone may sometimes suffice ( 2 - 6 ) . We provide a practical framework to help clinicians decide whether a new diagnostic test can be adopted on the basis of evidence of test accuracy alone or if they need to wait for results from r and omized trials . A Framework for Deciding if Evidence of Test Accuracy Will Suffice Studies of diagnostic test accuracy can suffice if clinicians already have evidence from r and omized trials showing that treatment of the cases detected by the diagnostic test improved patient outcomes ( Figure 1 ) . This approach may seem straightforward ; however , it requires a clear underst and ing of the proposed use and benefits of the new test , as well as careful consideration of whether the cases detected are representative of the patients included in treatment trials . Figure 1 . Trial evidence versus linked evidence of test accuracy and treatment efficacy . The benefits of a new diagnostic test will vary according to how it is used . Investigators of a new diagnostic test need to explicitly state who will be tested , where the new test will fit in the existing diagnostic pathway , and what tests it will supplement or replace . This information will allow them to identify the expected benefits of adopting the new test and , therefore , the most relevant questions to ask to assess its value . Test attributes generally fall into 3 categories : 1 ) The test is safer or is less costly ; 2 ) the test is more specific ( excludes more cases of nondisease ) and thus avoids unnecessary treatment ; and 3 ) the test is more sensitive ( detects more cases of disease ) and thus promotes more appropriate treatment . We propose a simple sequence of questions to guide decisions about whether evidence of test accuracy will suffice for each of these 3 categories ( Figure 2 ) . The first step in assessing a new diagnostic test is to classify it according to whether it is more sensitive than the old test . We describe the key concepts of this framework using simple examples to describe situations where the new test offers better safety or specificity with similar sensitivity , followed by consideration of situations where the test is more sensitive . We also consider other , more complex scenarios . In each of these examples , we have some existing evidence of treatment efficacy for cases detected by an old test , and therefore , the rationale for testing has already been established . Figure 2 . Assessing new tests using evidence of test accuracy , given that treatment is effective for cases detected by the old test . When a New Test Has Similar Sensitivity to an Old Test If a new diagnostic and old diagnostic test have similar sensitivity , it is generally reasonable to assume that they will detect the same true cases of disease . However , a new test may offer other positive attributes , such as better safety or more specificity than an old test . If studies of test accuracy show that the new test offers other positive attributes without a loss of sensitivity , it is logical to assume that cases detected by either test will show the same response to treatment . Therefore , new trials assessing treatment efficacy in the cases detected by the new test are not needed . When a new test and an old test show similar sensitivity and specificity , the value of the new test corresponds to the benefits of avoiding the adverse events or costs associated with the old test . For example , Doppler ultrasonography has been adopted as a less invasive replacement for venography for diagnosis of deep venous thrombosis ( 7 ) . Given that trials have shown that treatment of this condition is effective ( 8) , studies of test accuracy showing that Doppler ultrasonography and venography have similar sensitivity and specificity suffice to determine the value of the new test ( Table , example 1 ) . Table . New Diagnostic Test Assessment Framework and Examples If a new test is more specific than an old test , it avoids the harms of unnecessary further investigation or treatment . In this scenario , evidence showing that the new test has similar sensitivity but better specificity than the old test will suffice to determine the new test 's value . For example , new immunochemical fecal occult blood testing kits have been proposed to offer increased specificity , without a loss of sensitivity , for detecting human blood , reducing the high false-positive rate of the older guaiac-based test kits ( 9 ) . Given that trials have already shown the benefit of detecting colorectal cancer with guaiac test kits , studies of test accuracy will suffice to determine whether the immunochemical tests have increased specificity without any substantial loss in sensitivity ( Table , example 2 ) . Our assessment is more complex when we consider a new test that involves a tradeoff between positive and negative attributes . We deal with this situation later . When the New Test Is More Sensitive than the Old Test If a new test is more sensitive than an old test but has similar specificity , its value is directly related to the treatment response in the extra cases detected . If treatment response has already been assessed by treatment trials enrolling patients detected by the new test , decisions to use the test will be based on whether these trials showed that treatment improves patient outcomes . In this instance , evidence of test accuracy linked with evidence of treatment efficacy replaces the need for new r and omized trials ( Figure 1 ) . There will also be a good match between tested and treated population s if the results for patients identified by a new test are analyzed in a treatment trial as potential predictors of treatment response . For example , trials of adjuvant tamoxifen among women with early breast cancer have shown that the estrogen receptor status of the tumor determines its response to treatment ( 10 ) . These trials demonstrate the clinical value of testing for estrogen receptor status , as well as the effectiveness of tamoxifen therapy . However , more commonly , treatment trials have only enrolled cases detected by an old test . In these situations , clinicians need to consider whether the results apply to cases detected by the new test . Assessing Whether the Extra Cases Detected by a New , More Sensitive Test Respond to Treatment Clinicians first need to ask whether the extra cases detected by a new diagnostic test represent the same spectrum or subtypes of disease as those included in treatment trials . If they do , then r and omized trials may not be required ( Figure 2 ) . If they do not , or if clinicians can not be certain that they do , then clinicians also need to ask whether treatment response is known to be similar across the range of disease spectrum or subtype . These considerations are important regardless of the magnitude of the difference in sensitivity between tests . At one extreme , a good match between tested and treated population s is possible if the reference st and ard used to determine test sensitivity and specificity is also the starting point for trials conducted in similar population s. For example , computed tomography colonography is more sensitive for the detection of large colorectal polyps when scanning is performed with the patient in prone and supine positions versus supine positioning alone , without reduced specificity ( 11 ) . Treatment trials showing improved survival following the early detection and treatment of colorectal polyps have been based on cases detected by colonoscopy , the reference st and ard for the computed tomography colonography accuracy studies . All of these tests are used to identify the same disease characteristic ( adenomatous colorectal polyps ) and spectrum of disease ( classified by polyp size ) , so it is reasonable to conclude that computed tomography colonography with dual positioning will improve patient outcomes compared with supine positioning alone ( Table , example 3 ) . At the other extreme , a good match between tested and treated population s will not be possible if a new test measures a different biological characteristic to define disease and leads to a different selection of cases for treatment . For example , a new BACKGROUND Screening for cervical cancer based on testing for human papillomavirus ( HPV ) increases the sensitivity of detection of high- grade ( grade 2 or 3 ) cervical intraepithelial neoplasia , but whether this gain represents overdiagnosis or protection against future high- grade cervical epithelial neoplasia or cervical cancer is unknown . METHODS In a population -based screening program in Sweden , 12,527 women 32 to 38 years of age were r and omly assigned at a 1:1 ratio to have an HPV test plus a Papanicolaou ( Pap ) test ( intervention group ) or a Pap test alone ( control group ) . Women with a positive HPV test and a normal Pap test result were offered a second HPV test at least 1 year later , and those who were found to be persistently infected with the same high-risk type of HPV were then offered colposcopy with cervical biopsy . A similar number of double-blinded Pap smears and colposcopies with biopsy were performed in r and omly selected women in the control group . Comprehensive registry data were used to follow the women for a mean of 4.1 years . The relative rates of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected at enrollment and at subsequent screening examinations were calculated . RESULTS At enrollment , the proportion of women in the intervention group who were found to have lesions of grade 2 or 3 cervical intraepithelial neoplasia or cancer was 51 % greater ( 95 % confidence interval [ CI ] , 13 to 102 ) than the proportion of women in the control group who were found to have such lesions . At subsequent screening examinations , the proportion of women in the intervention group who were found to have grade 2 or 3 lesions or cancer was 42 % less ( 95 % CI , 4 to 64 ) and the proportion with grade 3 lesions or cancer was 47 % less ( 95 % CI , 2 to 71 ) than the proportions of control women who were found to have such lesions . Women with persistent HPV infection remained at high risk for grade 2 or 3 lesions or cancer after referral for colposcopy . CONCLUSIONS The addition of an HPV test to the Pap test to screen women in their mid-30s for cervical cancer reduces the incidence of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected by subsequent screening examinations . ( Clinical Trials.gov number , NCT00479375 [ Clinical Trials.gov ] . ) |
12,985 | 19,593,108 | However , none of the comparative studies of pedicle and free TRAM procedures found significant differences in abdominal wall function between the 2 groups .
Free TRAM groups experienced minimal deficit in rectus muscle function , whereas DIEP flaps returned to baseline for both rectus and oblique muscle function .
Subjective measures of abdominal wall function were similar across unipedicle TRAM , free TRAM , and DIEP flap procedures .
Patients with bilateral pedicle or free TRAM reconstruction also experienced a significant decrease in the ability to perform sit-ups and a significant decrease in activities of daily living , recreational , and laborious activities .
With the exception of those who had bipedicled TRAM or bilateral free TRAM procedures , most women reported return to their preoperative function without a decrease in their ability to perform activities of daily living .
Although some studies report an objective advantage of DIEP flaps , this does not appear to translate to detriments in the performance of activities of daily living . | Perforator flap breast reconstruction potentially offers patients greater postoperative abdominal strength compared with traditional TRAM techniques .
Our purpose was to perform a systemic review of the published literature regarding abdominal wall function following breast reconstruction and compare outcomes between pedicle TRAM , free TRAM , and perforator flap procedures . | Objective : To prospect ively evaluate the psychosocial outcomes and body image of patients 2 years postmastectomy reconstruction using a multicenter , multisurgeon approach . Background : Although breast reconstruction has been shown to confer significant psychosocial benefits in breast cancer patients at year 1 postreconstruction , we considered the possibility that psychosocial outcomes may remain in a state of flux for years after surgery . Methods : Patients were recruited as part of the Michigan Breast Reconstruction Outcome Study , a 12 center , 23 surgeon prospect i ve cohort study of mastectomy reconstruction patients . Two-sided paired sample t tests were used to compare change scores for the various psychosocial subscales . Multiple regression analysis was used to determine whether the magnitude of the change score varied by procedure type . Results : Preoperative and postoperative year 2 surveys were received from 173 patients ; 116 with immediate and 57 with delayed reconstruction . For the immediate reconstruction cohort , significant improvements were observed in all psychosocial subscales except for body image . This occurred essentially independent of procedure type . In the cohort with delayed reconstruction , significant change scores were observed only in body image . Women with transverse rectus abdominis musculocutaneous flaps had significantly greater gains in body image scores ( P = 0.003 and P = 0.034 , respectively ) when compared with exp and er/implants . Conclusions : General psychosocial benefits and body image gains continued to manifest at 2 years postmastectomy reconstruction . In addition , procedure type had a surprisingly limited effect on psychosocial well being . With outcomes evolving beyond year 1 , these data support the need for additional longitudinal breast reconstruction outcome studies Although it is thought that transverse rectus abdominis muscle ( TRAM ) flap breast reconstruction produces excellent cosmetic results that are maintained over the long term , there is little objective evidence in the literature to support this . One hundred seventy‐one consecutive patients who underwent TRAM flap reconstruction were prospect ively analyzed over an 8‐year period to assess their morbidity and late cosmetic outcome . The early patient complication rate ( < 2 months ) was 37.4 percent , the late hernia and fat necrosis rates ( > 2 months ) were 8.8 and 13.5 percent , respectively , and the contralateral symmetrization rate was 33.9 percent . The cosmetic results were evaluated prospect ively using an objective five‐point global scale . Each patient was scored at each visit once surgery was completed . Follow‐up continued until a flap was lost , a patient died , or the point of last patient contact was reached . Six patients died during the study . The actuarial percentage cosmetic outcome remained stable during the study period , with an acceptable result in 96.4 percent of patients at 2 years and in 94.2 percent of patients at 5 years . Only five patients in this series obtained poor cosmetic outcomes , with three due to substantial flap necrosis and two because of poor flap design . Two free TRAM flaps were also lost . Log‐rank analysis revealed that neither patient age nor timing of surgery significantly affected the cosmetic outcome . Single pedicle and supercharged ( single pedicle ) TRAM flaps produced slightly better results than bipedicle and free TRAM flaps . In this prospect i ve longitudinal study , TRAM flap reconstructions were shown to produce aesthetically pleasing results . Moreover , with long‐term follow‐up , it was demonstrated that these reconstructions maintained their stability . ( Plast . Reconstr . Surg . 107 : 1710 , 2001 . In the past decade , changing attitudes toward breast reconstruction among both patients and providers have led a growing number of women to seek breast reconstruction after mastectomy . Although investigators have documented the psychological , social , emotional , and functional benefits of breast reconstruction , little research has evaluated the effects of procedure choice on these outcomes . The current study prospect ively evaluated and compared psychosocial outcomes for three common options for mastectomy reconstruction : tissue exp and er/implant , pedicle TRAM , and free TRAM techniques . In a prospect i ve cohort design , patients undergoing postmastectomy reconstruction for the first time with exp and er/implant , pedicle TRAM , or free TRAM procedures were recruited from 12 centers and 23 plastic surgeons in the United States and Canada . Before reconstruction and at 1 year after reconstruction , patients were evaluated by a battery of question naires consisting of both generic and condition-specific surveys . Outcomes assessed included emotional well-being , vitality , general mental health , social functioning , functional well-being , social well-being , and body image . Baseline ( preoperative ) scores and the change in scores ( the difference between postoperative and preoperative scores ) were compared across procedure types using t tests and analysis of covariance . Preoperative and 1-year postoperative surveys were obtained from 273 patients . Procedure type was reported in 250 patients , of whom 56 received implant reconstructions , 128 pedicle TRAM flaps , and 66 free TRAM flaps . A total of 161 immediate and 89 delayed reconstructions were performed . Among women receiving immediate reconstruction , significant improvements were observed in all psychosocial variables except body image . However , no significant effects of procedure type on these changes over time existed . Similarly , delayed reconstruction patients had significant increases in emotional well-being , vitality , general mental health , functional well-being , and body image . Although the choice of reconstructive technique did not significantly impact most of these outcomes , significant differences existed among procedure types for three psychosocial subscales . Patients undergoing delayed exp and er/implant reconstructions reported greater improvements in vitality and social well-being relative to women receiving delayed TRAM procedures . By contrast , delayed TRAM patients noted significantly greater gains in body image compared with women choosing delayed exp and er-implant reconstruction . The authors conclude that both immediate and delayed breast reconstructions provide substantial psychosocial benefits for mastectomy patients . Although the choice of reconstructive procedure does not seem to significantly affect improvements in psychosocial status with immediate reconstruction , our data suggest that procedure type does have a significant effect on gains in vitality and body image for women undergoing delayed reconstruction BACKGROUND Previously , we found patient satisfaction with breast reconstruction at postoperative year 1 significantly higher in the autogenous tissue compared with the exp and er/implant population . But breast reconstructive procedures have different " aging " processes , and the point at which outcomes stabilize is unclear . So we evaluated patient satisfaction with breast reconstruction at postoperative year 2 and compared the results with those from our previous study . STUDY DESIGN As part of the Michigan Breast Reconstruction Outcomes Study , women undergoing mastectomy reconstruction ( including exp and er/implants and pedicle and free transverse rectus abdominis musculocutaneous flaps [ TRAM ] ) were prospect ively evaluated . Preoperatively and at postoperative years 1 and 2 , women completed a question naire that collected a variety of vali date d health status information . The postoperative question naire had an additional seven items assessing both general and esthetic satisfaction as separate subscales . To assess the effects of procedure on satisfaction and control for possible confounding , multiple logistic regression was used . RESULTS At year 2 , patients with TRAM flaps ( both free and pedicle ) continued to have higher levels of esthetic satisfaction compared with exp and er/implant patients ( odds ratio 2.8 , p < 0.01 ) . But no significant differences were appreciated in esthetic satisfaction between women with free and pedicle TRAM flaps . In regard to general satisfaction , the type of reconstruction ( exp and er/implant , pedicle TRAM , and free TRAM ) had no statistically significant effect . CONCLUSIONS At postoperative year 2 , procedural differences initially found in women 's general satisfaction with breast reconstruction diminish . Specifically , women with pedicle TRAM flaps , free TRAM flaps , and exp and er/implants had similar levels of general satisfaction . But at year 2 , patients continue to be more esthetically satisfied with autogenous tissue than with exp and er/implant reconstructions Twenty-seven free transverse rectus abdominis musculocutaneous ( TRAM ) and 16 pedicled TRAM flap breast reconstruction patients were studied for 7 to 41 months ( mean , 23 months ) postoperatively to compare abdominal sequelae after these two operations . The patient groups were demographically similar ; mean age was 47 years in both groups . Subjective grading of the results was similar in both groups . The incidence of minor lower abdominal bulges was higher ( 44 % , 7/16 ) in the pedicled group than in the free TRAM flap group ( 4 % , 1/27 ) . No hernias were found . Delayed healing of the abdominal scar occurred in 3 free TRAM flap and 1 pedicled TRAM flap patients . Two free TRAM flap ( 8 % ) and 7 pedicled TRAM ( 44 % ) flap patients had minor edge necrosis of the breast . Trunk strength was tested using an isokinetic device ( Lido Multi Joint II ) , and peak torque for flexion ( mean , 111 Nm ± 25 Nm in the free TRAM flap group and 123 Nm ± 28 Nm in the pedicled TRAM flap group ) and extension ( mean , 144 Nm ± 38 Nm and 167 Nm ± 45 Nm ) were measured . No statistical differences occurred between these groups . Sit-up performance was tested and grade d from 1 to 6 . Both groups performed equally ( 4.8 and 4.8 ) and within normal values for this age group . Ultrasonography of the rectus muscles revealed that in the free TRAM flap group , the rectus muscle of the operated side was significantly thinner ( cranial segment 6.8 mm vs. 7.8 mm , p < 0.05 ) , thus the harvesting of a segment of muscle below the umbilicus seems to disturb the quality of the entire muscle . The mean size of the muscular defect in the free TRAM flap group was 4.3 x 6.1 cm . In this study no differences in patient satisfaction or trunk strength could be found between free and pedicled TRAM flap patients Background : Functional outcomes in breast reconstruction are important quality measures and aid in patients ' decision-making process . To address the concerns of abdominal wall morbidity with transverse rectus abdominis musculocutaneous ( TRAM ) flap reconstructions , the authors prospect ively evaluated the long-term effects of postmastectomy breast reconstruction on trunk function using objective clinical measures . Methods : Using a multicenter prospect i ve cohort design , they recruited women undergoing first-time immediate or delayed breast reconstructions from 12 centers and 23 plastic surgeons . Trunk functional data , objective ly measured with Cybex machines , for patients with an exp and er/implant , pedicle TRAM , and free TRAM reconstructions were evaluated preoperatively and at postoperative years 1 and 2 in 183 patients . The effects of procedure type , timing , and laterality on trunk peak torque and range of motion were analyzed using linear regression . Results : At 2 years postoperatively , procedure type , timing , and laterality did not significantly affect the range of motion for trunk flexion and extension . Peak torque for trunk flexion at year 2 was significantly decreased in patients with TRAM compared with exp and er/implant reconstructions ( p < 0.05 ) , with a 6 to 19 percent decrease in flexion peak torque . However , no significant difference in flexion peak torque was found between patients with free and pedicle TRAM reconstructions . Conclusions : The authors found that ( 1 ) breast cancer patients with TRAM reconstructions had a less than 20 percent long-term deficit in trunk flexion peak torque and ( 2 ) there was no significant difference in trunk function between patients receiving pedicle and free TRAM reconstructions Objective The authors prospect ively studied the impact of immediate breast reconstruction on patients undergoing mastectomy . Summary Background Data Despite the advocation of a breast-conserving approach to the treatment of breast cancer , many women continue to medically require or choose mastectomy for the treatment of breast cancer . In recent years , immediate breast reconstruction has become an alternative to either mastectomy alone or to delayed reconstruction . Methods A prospect i ve data base of 216 patients who underwent mastectomy with immediate reconstruction was established . In this series , 94 procedures involved implants or tissue exp and ers , and 124 tissue transfers were performed . Results The overall complication rate was 15.3 % ; only 9 % of patients who underwent autologous tissue transfers required secondary procedures . When implants were performed , the overall rate of prosthetic loss was 8 % . The majority of patients ( n = 101 ) underwent transverse rectus abdominis musculocutaneous ( TRAM ) flaps . Twenty-six of the 38 ( 17.5 % ) patients who required transfusion were from this group . Partial flap losses in this group ( 7 % ) were correlated to a history of heavy smoking . With a median follow-up of 33.2 months , only two patients had recurred locally . According to patient opinion , autologous tissue transfers result ed in a statistically better cosmetic result . Conclusions Immediate reconstruction can be performed safely and with excellent cosmetic results Abdominal weakness is a known potential complication of breast reconstruction with a pedicled or free TRAM flap . It has been presumed that the DIEP flap , which involves no muscle resection , does not compromise abdominal muscle strength but little objective research exists to substantiate this . The aims of this retrospective study were to compare abdominal muscle strength following free TRAM flap and DIEP flap , to compare both groups with a control group and to establish the effect of both procedures on functional activities . Fifty women ( 23 with a DIEP flap , 27 with a free TRAM flap ) plus 32 non-operated controls underwent assessment of their abdominal and back extensor muscle strength on a KIN COM isokinetic dynamometer . Two question naires were used to establish the impact on function . The TRAM flap group had significant weakness of the abdominal and back extensor muscles compared with the DIEP flap group and the control group . The trend was for the DIEP flap group to have weaker abdominal muscles than the control group . There was a higher level of abdominal pain and a greater number of reported functional difficulties in the TRAM flap group than in the DIEP flap group . This study demonstrates that whilst the DIEP flap can reduce the strength deficit caused by the free TRAM flap , abdominal weakness can still result from the DIEP flap . A r and omised controlled trial is currently underway to investigate the effect of preoperative abdominal exercises in preventing/minimising postoperative abdominal muscle weakness in this group Abdominal wall function is a major concern for plastic surgeons performing breast reconstruction with TRAM flaps . The deep inferior epigastric perforator ( DIEP ) free flap spares the whole rectus abdominis muscle , includes skin and fat only , and therefore , preserves adequate abdominal wall competence . Between January of 1995 and May of 1997 , a total of 50 breast reconstructions in 42 patients were performed by using the DIEP flap . Eight patients had bilateral procedures . Five breast reconstructions were immediate and 45 were delayed . All patients were collected prospect ively and no patients were excluded from this study . The average age of patients was 47 years ( range , 22 to 59 years ) and the average weight was 65 kg ( range , 51 to 103 kg ) . Seventy percent of patients had one or more risk factors for TRAM flap reconstruction . The mean postoperative follow-up period was 13 months ( range , 3 to 30 months ) . Twenty consecutive patients ( 17 single and 3 bilateral DIEP flap breast reconstructions ) within this group underwent evaluation of their abdominal wall function preoperatively and then 3 and 6 months postoperatively by using Lacote 's muscle grading system . Average flap harvesting time was 120 minutes and average blood loss was 420 cc . Total flap loss and partial necrosis occurred in one ( 2 percent ) and three flaps ( 6 percent ) , respectively . Abdominal wound infection occurred in seven patients ( 17 percent ) . Unfortunately , one patient died of adult respiratory distress syndrome on the seventh postoperative day . Fat necrosis was found in three flaps ( 6 percent ) . Postoperative abdominal wall examination did not reveal any hernia , but bulging was found in two patients ( 5 percent ) . All patients were able to resume their daily activities . Abdominal wall function tests in the series of 20 patients showed that all patients had reached or even improved their preoperative level of upper and lower rectus muscle function 6 months after the operation . The external oblique muscles were the most affected by the procedure of flap harvesting , but only two patients ( 10 percent ) were found to have a measurable impairment after 6 months . Patient satisfaction with the reconstructed breast and the donor site was rated high . The free DIEP flap is , therefore , a reliable and valuable method of breast reconstruction . The donor site morbidity was decreased , and the more tedious flap dissection did not affect the overall outcome & NA ; Abdominal‐wall function was evaluated preoperatively and at intervals postoperatively in 25 consecutive patients undergoing breast reconstruction with transverse rectus abdominis myocutaneous ( TRAM ) flaps ( single‐pedicled TRAM flap , 14 patients ; free TRAM flap , 9 patients ; and bilateral free TRAM flaps , 2 patients ) . Objective measures of abdominal‐wall function were performed with the B200 Isostation , a triaxial dynamometer . In addition , the patients were assessed by a physical therapist and filled out an activity question naire at each postoperative examination . Tests of abdominal‐wall function demonstrated the greatest decrease in performance at the 6‐week postoperative tests of flexion . The maximum isometric flexion torque of the pedicled TRAM flap group decreased to 58 ± 10 percent , while the unilateral free TRAM flap group average was 87 ± 11 percent of baseline . For the pedicled TRAM flap group this difference was significant ( p = 0.004 ) . By the 6‐month evaluation , the maximum isometric flexion torque increased for both the pedicled and the free TRAM flap groups to 89 ± 13 percent and 93 ± 8 percent of baseline , respectively . The physical therapist evaluation of abdominal‐wall strength and the activity question naire data showed no statistically significant differences between groups or over time . Rectus abdominis muscle harvest for pedicled TRAM flaps causes a greater insult to the abdominal wall than does free TRAM flap harvest . The ultimate clinical effect of the sacrifice of even an entire rectus abdominis muscle appears to be well tolerated by most patients . This is the first prospect i ve outcome study of abdominal‐wall function in TRAM flap patients . The clinical implication s of this information will be discussed A prospect i ve study was design ed to evaluate the possible changes in abdominal wall strength following free transverse rectus abdominis musculocutaneous ( TRAM ) flap surgery for breast reconstruction . Twenty-two patients were examined 1 day before surgery , and at 3 , 6 , and 12 months postoperatively . Trunk muscle strength was measured by the same physiotherapist using an isokinetic dynamometer ( Lido Multi Joint II , Loredan Biomedical Inc. , Davies , CA ) . The peak torque and average torque for both flexion and extension at 60 degrees per second angular velocity were recorded from the curves obtained . There was a significant reduction in trunk flexion strength at 3 months postoperatively ( peak torque mean , 92 % of the preoperative value ; p = 0.04 ) , but this was corrected by 6 months ( mean , 96 % ) , and improved to 98 % by 12 months . The patient 's ability to do curled trunk sit-ups was evaluated by the same physiotherapist and grade d on a scale from 1 to 6 . In 9 of 19 patients the operation had no effect on sit-up performance during follow-up . In 10 of 19 patients there was a reduction of one or two grade s at 3 months that did not improve by 12 months . Magnetic resonance imaging of the abdominal wall was performed on 9 patients . The mean area of the upper third of both rectus muscles was measured on the axial images . At 3 months postoperatively the mean area of the upper third of the donor muscle was significantly larger than the contralateral ( p = 0.03 ) . There was no difference in size at 6 months , and by 12 months the donor side was smaller . This prospect i ve study shows that harvesting of a free TRAM flap can cause a sub clinical reduction in abdominal strength , although this was not noticed by the patients themselves & NA ; The main disadvantage when the transverse rectus abdominis musculocutaneous ( TRAM ) flap is used for breast reconstruction is the potential for weakening of the abdominal wall . This prospect i ve study was initiated to objective ly evaluate abdominal muscle strength after pedicled and free TRAM flap breast reconstructions over time . Twenty‐three patients with pedicled TRAM flaps and 19 patients with free TRAM flaps were included . A dynamic dynamometer system , KIN‐COM , was used to measure maximal voluntary trunk flexor and extensor strength preoperatively and 6 and 12 months postoperatively . The patients ' subjective opinions 1 year postoperatively were recorded by means of a question naire . A transient decrease in abdominal strength , in both groups , occurred at 6 months but was essentially regained at 12 months . The use of a pedicled or free TRAM flap did not influence postoperative abdominal strength per se . The balance between the abdominal strength and back strength remained in the free flap group but was altered postoperatively in the pedicled flap group ; back strength was increased and remained so after 12 months . The difference between the two procedures is relatively small compared with individual variations , indicating that there are more important factors than the kind of surgery influencing the restoration of muscle strength . The question naire revealed a greater occurrence of abdominal wall bulging in the free flap group ( 82 percent ) versus 48 percent in the pedicled flap group . No postoperative differences regarding exercise frequency or sensitivity of the abdominal wall were found between the pedicled and free TRAM flap groups . ( Plast . Reconstr . Surg . 102 : 1508 , 1998 . This study was undertaken to demonstrate that the deep inferior epigastric perforator ( DIEP ) flap can provide the well-known advantages of autologous breast reconstruction with lower abdominal tissue while avoiding the abdominal wall complications of the transverse rectus abdominis myocutaneous ( TRAM ) flap . Eighteen unilateral free DIEP flap breast reconstruction patients were assessed 12 - 30 months ( mean 17.8 months ) after surgery . Clinical examination , physical exercises and isokinetic dynamometry were performed preoperatively and two months and one year postoperatively . Intraoperative segmental nerve stimulation , visual evaluation and postoperative CT scans were also used to quantify the damage to the rectus muscle . The 18 patients were then compared with 20 free TRAM flap patients and 20 non-operated controls . Two DIEP flap patients presented with abdominal asymmetry . A limited decrease of trunk flexing strength was noticed but rotatory function was intact . Ten of the TRAM flap patients had umbilical or abdominal asymmetry , bulging or hernias . TRAM flap patients showed a statistically significant reduction in strength to flex and to rotate the upper trunk compared to both the one year postoperative DIEP flap group and the control group . The answers to a question naire revealed impairment of activities of daily living for some TRAM flap patients while the activities of all DIEP flap patients were unaffected . Our data demonstrate that the free DIEP flap can limit the surgical damage to the rectus abdominis and oblique muscles to an absolute minimum . We believe it is worthwhile to spend extra operative time , the main disadvantage of this technique , to limit late postoperative weakness of the lower abdominal wall In today ’s increasingly competitive health care marketplace , consumer satisfaction has become an important measure of quality . Furthermore , measures of satisfaction with treatment interventions are influential factors in determining patients ’ and payers ’ choices of health care . This study sought to evaluate satisfaction with postmastectomy breast reconstruction and to assess the effects of procedure type and timing on patient satisfaction . As part of the Michigan Breast Reconstruction Outcome Study , patients undergoing first-time mastectomy reconstruction were prospect ively evaluated , including cohorts of women choosing exp and er/implant , pedicle TRAM flap , and free TRAM flap procedures . Preoperatively and 1 year postoperatively , participants completed a question naire that collected a variety of health status information . The postoperative question naire had an additional seven items assessing both general satisfaction with reconstruction ( five items ) and aesthetic satisfaction ( two items ) as separate subscales . Patients were asked to respond to each item using a five-point Likert scale . Item responses ranged from 1 , indicating high satisfaction , to 5 , reflecting low satisfaction . In the data analysis , only patients responding with a 1 or 2 for all of the items within a subscale were classified as “ satisfied ” for the subscale . To assess the effects of procedure type ( implant , pedicle TRAM flap , and free TRAM flap ) and timing ( immediate versus delayed ) on satisfaction and to control for possible confounding effects from other independent variables , multiple logistic regression was employed . In our analysis , odds ratios and associated 95 percent confidence intervals were calculated for each independent variable in the regression . Statistical significance was design ated at the p ≤ 0.05 level . A total of 212 patients were followed during the period of 1994 to 1997 , including 141 immediate and 71 delayed reconstructions . The study population consisted of 49 exp and er/implant , 102 pedicle TRAM flap , and 61 free TRAM flap reconstruction patients . The analysis showed a significant association between procedure type and patient satisfaction . TRAM flap patients ( both free and pedicle ) appeared to have significantly greater general and aesthetic satisfaction compared with exp and er/implant patients ( p = 0.03 and 0.001 , respectively ) . Furthermore , pedicle TRAM flap patients were more aesthetically satisfied than those with free TRAM flaps ( p = 0.072 ) . The other independent variables of age and procedure timing did not appear to significantly affect either general or aesthetic satisfaction . However , preoperative physical activity was positively correlated with general satisfaction at the p = 0.034 level . The choice of procedure seems to have a significant effect on both aesthetic and general patient satisfaction with breast reconstruction . In this study , autogenous tissue reconstructions produced higher levels of patient aesthetic and general satisfaction compared with implant techniques . Pedicle and free TRAM flap patients do not seem to differ significantly in general satisfaction . However , women receiving pedicle TRAM flaps reported greater aesthetic satisfaction compared with patients undergoing free TRAM flaps . Furthermore , patient age and procedure timing may not have an effect on patient satisfaction with breast reconstruction |
12,986 | 26,613,036 | The strongest evidence is for the effects of aerobic exercise on improving physical fitness , muscular strength and quality of life in dialysis patients .
The benefits of exercise in dialysis patients are well established , supporting the prescription of physical activity in their regular treatment . | Chronic kidney disease ( CKD ) is a public health problem .
Although physical activity is essential for the prevention and treatment of most chronic diseases , exercise is rarely prescribed for CKD patients .
The objective of the study was to search for and appraise evidence on the effectiveness of exercise interventions on health endpoints in CKD patients . | BACKGROUND Patients with chronic heart failure ( CHF ) have a continuing high mortality . Autonomic dysfunction may play an important role in the pathophysiology of cardiac death in CHF . UK-HEART examined the value of heart rate variability ( HRV ) measures as independent predictors of death in CHF . METHODS AND RESULTS In a prospect i ve study powered for mortality , we recruited 433 out patients 62+/-9.6 years old with CHF ( NYHA functional class I to III ; mean ejection fraction , 0.41+/-0.17 ) . Time-domain HRV indices and conventional prognostic indicators were related to death by multivariate analysis . During 482+/-161 days of follow-up , cardiothoracic ratio , SDNN , left ventricular end-systolic diameter , and serum sodium were significant predictors of all-cause mortality . The risk ratio for a 41.2-ms decrease in SDNN was 1.62 ( 95 % CI , 1.16 to 2.44 ) . The annual mortality rate for the study population in SDNN subgroups was 5.5 % for > 100 ms , 12.7 % for 50 to 100 ms , and 51.4 % for < 50 ms . SDNN , creatinine , and serum sodium were related to progressive heart failure death . Cardiothoracic ratio , left ventricular end-diastolic diameter , the presence of nonsustained ventricular tachycardia , and serum potassium were related to sudden cardiac death . A reduction in SDNN was the most powerful predictor of the risk of death due to progressive heart failure . CONCLUSIONS CHF is associated with autonomic dysfunction , which can be quantified by measuring HRV . A reduction in SDNN identifies patients at high risk of death and is a better predictor of death due to progressive heart failure than other conventional clinical measurements . High-risk subgroups identified by this measurement are c and i date s for additional therapy after prescription of an ACE inhibitor Background Functional limitations , altered cardiac autonomic activity , and psychological distress are known disorders in chronic hemodialysis ( HD ) patients , relating to increased morbidity and mortality . The aim of this study was to examine the influence of an exercise training program on emotional parameters and heart rate variability ( HRV ) indices , as well as to determine whether emotional stress contributes to autonomic dysfunction in these patients . Methods Forty-four HD patients were r and omly assigned into group A ( 24 patients , aged 46.3 ± 11.2 years ) , who participated in a 1-year intradialytic exercise training program and group B ( 20 patients , aged 45.8 ± 10.8 years ) , who were used as controls . At baseline and a year after , measures of HRV were obtained for the estimation of st and ard deviation of RR intervals , the mean square successive differences , percentage of RR intervals differing by more than 50 ms from the preceding RR interval ( pNN50 ) , and low to high frequency components . Emotional parameters ( Beck Depression Inventory – BDI and Hospital Anxiety and Depression Scale – HADS ) were also assessed by vali date d question naires . Moreover , all patients performed a spiroergometric study for the estimation of VO2peak . Results At baseline , all measurements were similar in the two groups and remained almost unchanged after a year in group B. After a year of training , VO2peak increased from 16.79 ± 5.24 to 22.33 ± 4.90 ml/kg per min ( P > 0.001 ) in group A. Trained patients also showed an increase in st and ard deviation of RR intervals by 58.8 % ( P > 0.001 ) , the mean square successive differences by 68.1 % ( P > 0.001 ) , pNN50 by 23.5 % ( P > 0.001 ) , and a low to high frequency ratio by 17.3 % ( P > 0.001 ) . Finally , at the end of the study , group A showed a decrease in BDI score by 34.5 % ( P > 0.001 ) and HADS by 23.9 % ( P > 0.001 ) . Canonical correlation revealed significant inverse correlation among depression ( in BDI and HADS ) and HRV indices before and after exercise training . Conclusion Cardiac autonomic modulation seemed to be sensitive to the experience of persistent depression in HD patients . Significantly , exercise training reduced emotional distress and concomitantly improved HRV AIM To evaluate the effects of a yoga-based exercise program on pain , fatigue , sleep disturbance , and biochemical markers in hemodialysis patients . MATERIAL S AND METHODS In 2004 a r and omized controlled trial was carried out in the outpatient hemodialysis unit of the Nephrology Department , Uludag University Faculty of Medicine . Clinical ly stable hemodialysis patients ( n=37 ) were included and followed in two groups : the modified yoga-based exercise group ( n=19 ) and the control group ( n=18 ) . Yoga-based exercises were done in groups for 30 min/day twice a week for 3 months . All of the patients in the yoga and control groups were given an active range of motion exercises to do for 10 min at home . The main outcome measures were pain intensity ( measured by the visual analogue scale , VAS ) , fatigue ( VAS ) , sleep disturbance ( VAS ) , and grip strength ( mmHg ) ; biochemical variables-- urea , creatinine , calcium , alkaline phosphatase , phosphorus , cholesterol , HDL-cholesterol , triglyceride , erythrocyte , hematocrit -- were evaluated . RESULTS After a 12-week intervention , significant improvements were seen in the variables : pain -37 % , fatigue -55 % , sleep disturbance -25 % , grip strength + 15 % , urea -29 % , creatinine -14 % , alkaline phosphatase -15 % , cholesterol -15 % , erythrocyte + 11 % , and hematocrit count + 13 % ; no side-effects were seen . Improvement of the variables in the yoga-based exercise program was found to be superior to that in the control group for all the variables except calcium , phosphorus , HDL-cholesterol and triglyceride levels . CONCLUSION A simplified yoga-based rehabilitation program is a complementary , safe and effective clinical treatment modality in patients with end-stage renal disease BACKGROUND The prevalence of obesity has markedly increased in patients with chronic kidney disease ( CKD ) . Studies on the impact of exercise focusing on obese CKD patients are scarce . Therefore , we aim ed to investigate the effect of aerobic exercise performed either in an exercise centre or at home on visceral fat in overweight non-dialysed CKD patients . METHODS Twenty-seven sedentary men ( 52.1 ± 9.5 years , body mass index 30.4 ± 3.8 kg/m(2 ) , estimated glomerular filtration rate ( eGFR ) 27.5 ± 11.6 mL/min ) were r and omly assigned to a centre-based exercise group ( n = 10 ) , home-based exercise group ( n = 8) or control group ( n = 9 ) . The aerobic training was prescribed according to ventilatory threshold and performed three times per week during 12 weeks . Body composition was assessed by dual energy X-ray absorptiometry ( DEXA ) and the distribution of abdominal fat by computed tomography . RESULTS In the centre-based group , visceral fat and waist circumference decreased 6.4 ± 6.4 mm ( P < 0.01 ) and 2.0 ± 2.3 cm ( P = 0.03 ) and leg lean mass increased 0.5 ± 0.4 kg ( P < 0.01 ) . No significant changes were observed in the home-based group . Visceral fat increased 5.0 ± 4.4 mm in the control group ( P = 0.01 ) . In relation to the control , a group-by-time interaction was significant for visceral fat and waist circumference for both exercise groups and for leg lean mass for the centre-based group . Mean blood pressure decreased in both exercise groups ( centre-based 13 % , P < 0.01 and home-based 10 % , P = 0.03 ) and eGFR increased 3.6 ± 4.6 mL/min ( P = 0.03 ) in the centre-based group . These parameters remained unchanged in the control group . CONCLUSIONS Centre-based aerobic exercise is an effective approach to reduce visceral fat besides promoting relevant clinical benefits in male overweight CKD patients BACKGROUND AND OBJECTIVES CKD is associated with poor cardiorespiratory fitness ( CRF ) . This predefined sub study determined the effect of exercise training and lifestyle intervention on CRF and explored the effect on cardiovascular risk factors and cardiac and vascular function . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Between February 2008 and March 2010 , 90 patients with stage 3 - 4 CKD were screened with an exercise stress echocardiogram before enrollment . Patients ( n=83 ) were r and omized to st and ard care ( control ) or lifestyle intervention . The lifestyle intervention included multidisciplinary care ( CKD clinic ) , a lifestyle program , and aerobic and resistance exercise training for 12 months . CRF ( peak Vo2 ) , left ventricular function , arterial stiffness , anthropometric , and biochemical data were collected at baseline and 12 months . RESULTS Ten percent of r and omized patients had sub clinical myocardial ischemia at screening and completed the study without incident . There was no baseline difference among 72 patients who completed follow-up ( 36 in the lifestyle intervention group and 36 in the control group ) . The intervention increased peak Vo2 ( 2.8±0.7 ml/kg per minute versus -0.3±0.9 ml/kg per minute ; P=0.004 ) . There was small weight loss ( -1.8±4.2 kg versus 0.7±3.7 kg ; P=0.02 ) but no change in BP or lipids . Diastolic function improved ( increased e ' of 0.75±1.16 cm/s versus -0.47±1.0 cm/s ; P=0.001 ) but systolic function was well preserved and did not change . The change in arterial elastance was attenuated ( 0.11±0.76 mmHg/ml versus 0.76±0.96 mmHg/ml ; P=0.01 ) . Δ peak Vo2 was associated with group allocation and improved body composition . CONCLUSIONS Exercise training and lifestyle intervention in patients with CKD produces improvements in CRF , body composition , and diastolic function Background : Dyslipidemia has been established as a well-known traditional risk factor for cardiovascular disease in chronic kidney disease patients . Aim : This study investigated the impact of Hatha yoga exercise on lipid parameters in patients with end-stage renal disease ( ESRD ) on hemodialysis . Material s and Methods : This prospect i ve r and omized study consisted of 33 ESRD patients in the Hatha yoga exercise group that was matched with 35 ESRD patients in the control group . Serum total cholesterol , triglycerides , low-density lipoprotein (LDL)-cholesterol , and high-density lipoprotein (HDL)-cholesterol were determined at baseline ( 0 month ) and after 4 months . Results : Comparing values after 4 months versus baseline in the prehemodialysis Hatha yoga exercise group , there was found a significant decrease in total cholesterol from 5.126 ± 0.092 mmol/l to 4.891 ± 0.072 mmol/l ( -4.58 % ; P = 0.0001 ) , triglycerides from 2.699 ± 0.078 mmol/l to 2.530 ± 0.063 mmol/l ( -6.26 % ; P = 0.0001 ) , LDL-cholesterol from 2.729 ± 0.083 mmol/l to 2.420 ± 0.066 mmol/l ( -11.32 % ; P = 0.0001 ) , and total cholesterol/HDL-cholesterol ratio from 5.593 ± 0.119 mmol/l to 4.907 ± 0.116 mmol/l ( -12.26 % ; P = 0.047 ) . For patients in the Hatha yoga exercise group , 51.5 % had normal total cholesterol at 0 month while 70.0 % had normal total cholesterol ( P < 0.05 ) after 4 four months and 54.5 % of patients had normal LDL-cholesterol at 0 month while 84.9 % had normal LDL-cholesterol after 4 months ( P < 0.05 ) . Conclusion : These findings suggest that Hatha yoga exercise has preventive and beneficial effects and may be a safe therapeutic modality in ESRD patients BACKGROUND Cardiovascular disease ( CVD ) mortality rates are greatly elevated in chronic kidney disease patients receiving maintenance haemodialysis therapy . The purpose of this study was to evaluate the efficacy of intradialytic endurance exercise training on novel risk factors that may contribute to this excessive CVD risk . METHODS Seventeen haemodialysis patients were r and omized to either an intradialytic exercise training ( cycling ) group ( EX ; n = 8) or a non-exercising control group ( CON ; n = 9 ) for 4 months . At baseline and following the intervention , we measured serum parameters related to CVD risk and renal function , used echocardiography to measure variables related to cardiac structure and function and assessed physical performance by a vali date d shuttle walk test . RESULTS Performance on the shuttle walk test increased by 17 % in EX ( P < 0.05 ) , but did not change in CON . There was no change in serum lipids or inflammatory markers ( C-reactive protein , interleukin-6 ) in either group . Serum thiobarbituric acid reactive substances , a marker of oxidative stress , were reduced by 38 % in EX ( P < 0.05 ) , but did not change in CON . In addition , serum alkaline phosphatase ( ALP ) , a putative risk factor for vascular calcification , was reduced by 27 % in EX ( P < 0.05 ) , but did not change in CON . There was no change in left atrial volume , left ventricular mass or myocardial performance index in either group . However , the thickness of the epicardial fat layer was reduced by 11 % in EX ( P < 0.05 ) , but did not change in CON . Furthermore , the change in physical performance was inversely correlated to the change in epicardial fat ( r = -0.63 ; P = 0.03 ) . CONCLUSIONS These results suggest that endurance exercise training may improve CVD risk in haemodialysis patients by decreasing novel risk factors including serum oxidative stress , ALP and epicardial fat PURPOSE To investigate the effect of progressive resistance training ( PRT ) on body composition , physical fitness , quality of life , lipid and nutritional profile of patients on hemodialysis ( HD ) . METHODS A non equivalent comparison group pretest and posttest design study was used with 40 participants who were r and omly assigned to the exercise group ( 20 participants ) and the comparison group ( 20 participants ) . The exercise group received PRT for 30 minutes per session , 3 sessions a week , for 12 weeks , while the comparison group received usual care . The PRT consisted of upper and lower body exercises using elastic b and s and s and bags . Outcome measures evaluated were : body composition , physical fitness , quality of life , and lipid profile . RESULTS Skeletal muscle mass , grip , leg muscle strength , and quality of life all improved significantly in the exercise group . Body fat rate , total cholesterol and triglyceride rate decreased significantly in the exercise group . CONCLUSION These results suggest that PRT improves body composition , physical fitness , quality of life , and lipid profile of patients on HD . PRT using elastic b and s and s and bags can be utilized as part of a regular care plan for these patients BACKGROUND The present study was design ed to determine the effect of short-term moderate-intensity exercise training on arterial stiffness in patients with chronic kidney disease ( CKD ) stage 3 . STUDY DESIGN R and omized controlled trial with a parallel-group design . SETTING & PARTICIPANTS Testing and training sessions were performed at Springfield College . 46 ( treatment group , n=25 ; control group , n=21 ) patients with CKD with diabetes and /or hypertension completed the study . INTERVENTION The aerobic training program consisted of 16 weeks of supervised exercise training at 50%-60 % peak oxygen uptake ( Vo2peak ) 3 times per week , while the control group remained sedentary . Identical testing procedures were performed following the 16-week intervention . OUTCOMES The primary outcome was arterial stiffness . Secondary outcomes were aerobic capacity , various blood parameters ( endothelin 1 , nitrate/nitrite , and high-sensitivity C-reactive protein ) , and health-related quality of life . MEASUREMENTS Arterial stiffness was assessed with aortic pulse wave velocity ( PWV ) , aerobic capacity by Vo2peak , blood parameters by enzyme-linked immunosorbent assays , and health-related quality of life by the 36-Item Short Form Health Survey ( SF-36 ) . Participants attended 4 sessions before being r and omly assigned to either the treatment or control group . Participants gave consent during the first session , whereas a grade d exercise test with measurement of Vo2peak was completed during the second session . During sessions 3 and 4 , aortic PWV was measured at rest prior to 40 minutes of either moderate-intensity exercise training or seated rest . A venous blood sample was obtained prior to exercise or rest and participants completed the SF-36 question naire . RESULTS 16 weeks of training led to an 8.2 % increase in Vo2peak for the treatment group ( P=0.05 ) , but no changes in aortic PWV . LIMITATIONS R and omization was not concealed and was violated on one occasion ; also , use of an indirect measurement of endothelial function and the short duration of the intervention . CONCLUSIONS Short-term moderate-intensity exercise training does not alter arterial stiffness in patients with CKD , but seems to reduce endothelin 1 levels BACKGROUND Kidney failure is associated with muscle wasting and physical impairment . Moderate- to high-intensity strength training improves physical performance , nutritional status and quality of life in people with chronic kidney disease and in dialysis patients . However , the effect of low-intensity strength training has not been well documented , thus representing the objective of this pilot study . METHODS Fifty participants ( mean + /- SD , age 69 + /- 13 years ) receiving long-term haemodialysis ( 3.7 + /- 4.2 years ) were r and omized to intra-dialytic low-intensity strength training or stretching ( attention-control ) exercises twice weekly for a total of 48 exercise sessions . The primary study outcome was physical performance assessed by the Short Physical Performance Battery score ( SPPB ) after 36 sessions , if available , or carried forward from 24 sessions . Secondary outcomes included lower body strength , body composition and quality of life . Measurements were obtained at baseline and at completion of 24 ( mid ) , 36 ( post ) and 48 ( final ) exercise sessions . RESULTS Baseline median ( IQR ) SPPB score was 6.0 ( 5.0 ) , with 57 % of the participants having SPPB scores below 7 . Exercise adherence was 89 + /- 15 % . The primary outcome could be computed in 44 participants . SPPB improved in the strength training group compared to the attention-control group [ 21.1 % ( 43.1 % ) vs. 0.2 % ( 38.4 % ) , respectively , P = 0.03 ] . Similarly , strength training participants exhibited significant improvements from baseline compared to the control group in knee extensor strength , leisure-time physical activity and self-reported physical function and activities of daily living ( ADL ) disability ; all P < 0.02 . Adverse events were common but not related to study participation . CONCLUSIONS Intra-dialytic , low-intensity progressive strength training was safe and effective among maintenance dialysis patients . Further studies are needed to establish the generalizability of this strength training program in dialysis patients Background Patients with obesity , diabetes , and chronic kidney disease ( CKD ) are generally physically inactive , have a high mortality rate , and may benefit from an exercise program . Methods We performed a 24-week r and omized controlled feasibility study comparing aerobic exercise plus optimal medical management to medical management alone in patients with type 2 diabetes , obesity ( body mass index [ BMI ] > 30 kg/m2 ) , and stage 2 - 4 CKD ( estimated glomerular filtration rate [ eGFR ] 15 - 90 mL/min/1.73 m2 with persistent proteinuria ) . Subjects r and omized to exercise underwent thrice weekly aerobic training for 6 followed by 18 weeks of supervised home exercise . The primary outcome variable was change in proteinuria . Results Seven subjects r and omized to exercise and 4 control subjects completed the study . Exercise training result ed in an increase in exercise duration during treadmill testing , which was accompanied by slight but insignificant decreases in resting systolic blood pressure and 24-hour proteinuria . Exercise did not alter GFR , hemoglobin , glycated hemoglobin , serum lipids , or C-reactive protein ( CRP ) . Caloric intake and body weight and composition also did not change with exercise training . Conclusion Exercise training in obese diabetic patients with CKD is feasible and may have clinical benefits . A large-scale r and omized controlled trial to determine the effects of exercise on renal functions , cardiovascular fitness , inflammation , and oxidative stress in diabetic patients with CKD is planned In r and omised controlled trials , allocation concealment ( separating the process of r and omisation from the recruitment of participants ) is important for rigorously design ed trials.1–4 In 1996 many major medical journals adopted the CONSORT statement ( whereby research ers have to include a short checklist of essential items and a flow diagram when reporting trials),5 and this move encouraged the reporting of allocation concealment . We review ed the prevalence of adequate allocation concealment and its association with the statistical significance of trial results . We search ed by h and four general medical journals ( the BMJ , JAMA , the Lancet , and the New Engl and Journal of Medicine ) to identify r and omised controlled trials published from January 2002 to December 2002 . We included articles if the authors reported that participants were r and omised and if the trial was published as a full report with the results of the main analyses . We categorised articles according to whether allocation concealment was adequate ( the person who executed the allocation sequence was different from the person who recruited Twenty-five hemodialysis patients were r and omized into comparable exercising ( E , N = 14 ) and sedentary control ( N = 11 ) groups . After baseline testing , training was 3 to 5 times weekly for a mean of 12 + /- 4 ( SD ) months . Maximal aerobic capacity increased 21 % ( P less than 0.01 ) , and the duration s for the grade d exercise stress test improved 19 % ( P less than 0.01 ) in E , but did not change in controls ( 8 + /- 4 months ) . Declining blood pressures in 8 hypertensive E led to reductions in antihypertensive medications ; no changes occurred in 9 hypertensive controls . Exercise lowered plasma total triglyceride levels 33 % ( 280 + /- 258 to 175 + /- 95 mg/dl ; P less than 0.01 ) , but no change occurred in total and low-density lipoprotein cholesterol concentrations . High-density lipoprotein cholesterol levels rose 16 % in E ( 31 + /- 9 to 36 + /- 12 mg/dl ; P less than 0.02 ) , but did not change in controls . An increase in the affinity of insulin for receptors on mononuclear cells was associated with a 20 % decrease in fasting plasma insulin levels ( 24 + /- 7 to 19 + /- 2 microU/ml , N = 8 ; P less than 0.05 ) and a 42 % improvement in glucose disappearance rates ( 1.9 + /- 1.0 to 2.6 + /- 1.2 % per min , N = 6 ) in E. There were no changes in the body weights or diets of the patients . A 27 % increase in red blood cell mass ( P less than 0.02 ) with no change in plasma volume result ed in a 27 % increase in hematocrit ( 24 + /- 3 % to 31 + /- 5 % , P less than 0.01 ) and a 20 % increase in hemoglobin ( 8 + /- 1 to 10 + /- 2 g/dl ; P less than 0.01 ) in E. ( ABSTRACT TRUNCATED AT 250 WORDS Objective : To assess the effects of intradialytic exercise training on health-related quality of life indices in haemodialysis patients . Subjects/ patients : Thirty-five patients on haemodialysis , with a mean ( SD ) age of 48.8 ( 13.9 ) years , volunteered to participate in the study . They were r and omized either to rehabilitation group ( group A : 19 patients ) , following a 10-month intradialytic exercise training programme or to control group ( group B : 14 patients ) . After the r and omization , two of the patients , one of each group , withdrew from the study for reasons unrelated to exercise training . Method : All patients at the beginning and the end of the study underwent clinical examination , laboratory tests and a treadmill exercise testing with spiroergometric study for the evaluation of their aerobic capacity ( Vo2peak ) . A formal psychosocial assessment , which included affective ( Beck Depression Inventory ) , health-related quality of life ( Quality of Life Index , Living Question naire of Minnesota , Life Satisfaction Index and Short Form-36 question naire ) and personality ( Eysenck Personality Question naire ) parameters , was evaluated at beginning and end of the study . The dose of erythropoietin was changed as needed , according to the level of the haemoglobin , aim ing to keep it at 11 ( 2 ) g/dL during the study . Results : Baseline values were similar between the two groups . After training in group A , Vo2peak was increased by 21.1 % ( P<0.05 ) and exercise time by 23.6 % ( P<0.05 ) . Moreover , group A showed a decrease in self-reported depression ( Beck Depression Index ) of 39.4 % ( P<0.001 ) . In addition , trained patients demonstrated a significant improvement in Quality of Life Index ( from 6.5 ( 1.8 ) to 9.0 ( 1.3 ) , P<0.001 ) and Life Satisfaction Index ( from 44.8 ( 8.6 ) to 53.0 ( 5.6 ) , P<0.001 ) , and an increase in the Physical Component Scale of the SF-36 ( from 40.5 ( 5.6 ) to 44.5 ( 5.5 ) , P<0.05 ) , while the Mental Component Scale remained unchanged . Multiple regression analysis indicated that the improvement in quality of life depended on the participation in exercise programmes , the effects of training and the reduction in the level of depression . No changes were observed in Eysenck Personality Question naire by the end of the study , while all the above parameters remained almost unchanged in the controls . Conclusion : The results demonstrated that intradialytic exercise training improves both physical functioning and psychological status in haemodialysis patients , leading to an improvement of patients ' quality of life BACKGROUND Individuals on hemodialysis have low physical function and activity levels . Clinical trials have shown improvements in these parameters with exercise programming . Pedometers have not been extensively evaluated in individuals on hemodialysis . This r and omized clinical trial compared the effects of intradialytic cycling versus a pedometer program on physical function , physical activity and quality of life . METHODS Sixty patients were r and omly assigned to two study groups . The ergometer group cycled during each hemodialysis session for 24 weeks . Pedometer participants followed a home-based walking program for 24 weeks . The primary outcome was aerobic capacity [ VO2peak and 6-minute walk ( 6MW ) test ] . Secondary outcomes included lower extremity strength [ sit-to-st and ( SS ) test ] , flexibility [ sit- and -reach ( SR ) test ] , physical activity ( accelerometer ) and health-related quality of life . Measurements were collected at baseline and at 12 and 24 weeks . RESULTS At 12 and 24 weeks , there was no significant change in the VO2peak or 6MW test between or within study groups . SS testing in the ergometer group improved from 10.2 ( SD 3.4 ) to 11.4 ( SD 2.5 ) cycles from baseline to 24 weeks ( P < 0.005 ) . Similarly , in the pedometer group , SS cycles improved from 10.1 ( SD 3.3 ) to 12.2 ( SD 3.5 ) ( P < 0.005 ) . The SR test also significantly improved over time in both the study groups . No significant changes were noted for other secondary outcomes . CONCLUSIONS Both intradialytic cycling and pedometer programming improved aspects of physical function . Neither intervention had a significant effect on aerobic capacity . No significant differences in any outcomes were identified between interventions groups Background . Restless leg syndrome ( RLS ) is one of the prevalent complaints of patients with end stage renal diseases suffering chronic hemodialysis . Although there are some known pharmacological managements for this syndrome , the adverse effect of drugs causes a limitation for using them . In this r and omized clinical trial we aim ed to find a nonpharmacological way to improve signs of restless leg syndrome and patients ' quality of life . Material and Methods . Twenty-six patients were included in the study and divided into 2 groups of control and exercise . The exercise group used aerobic exercise during their hemodialysis for 16 weeks . The quality of life and severity of restless leg syndrome were assessed at the first week of study and final week . Data were analyzed using SPSS software . Results . The difference of means of RLS signs at the first week of study and final week was −5.5 ± 4.96 in exercise group and −0.53 ± 2.3 in control group . There was not any statistical difference between control group and exercise group in quality of life at the first week of study and final week . Conclusions . We suggest using aerobic exercise for improving signs of restless leg syndrome , but no evidence was found for its efficacy on patient 's quality of life OBJECTIVES The purpose of this study is to determine whether a low-to-moderate intensity pre-conditioning exercise programme linked with exercise counselling could improve behavioural change , physical fitness , physiological condition and health-related quality of life of sedentary haemodialysis patients in The Netherl and s. METHODS Ninety-six haemodialysis patients of the Groningen Dialysis Center were r and omized into an exercise group ( n = 53 ) and a control group ( n = 43 ) . The exercise programme consists of cycling during dialysis together with a pre-dialysis strength training programme lasting 12 weeks . The intensity of the exercise programme is condition level 12 - 16 according to the rate of perceived exertion ( RPE ) . Motivational interviewing techniques were used for exercise counselling . Before and after the intervention , both groups were tested on behavioural change and physical fitness components such as reaction time , manual dexterity , lower extremity muscle strength and VO2 peak . Physiological conditions such as weight , blood pressure , haemoglobin and haematocrit values , cholesterol and Kt/V were obtained from the medical records . Health-related quality of life assessment included R AND -36 scores , symptoms and depression . RESULTS A group x time analysis with MANOVA ( repeated measures ) demonstrates that participation in a low-to-moderate intensity exercise programme linked with exercise counselling yields a significant increase in behavioural change , reaction time , lower extremity muscle strength , Kt/V and three components of quality of life , and no significant effects in the control group . CONCLUSION Participating in a low-to-moderate intensity pre-conditioning exercise programme showed beneficial effects on behavioural change , physical fitness , physiological conditions and health-related quality of life BACKGROUND Resistance exercise combined with intradialytic oral nutrition ( IDON ) supplementation improves net protein balance in the acute setting in chronic hemodialysis patients . We hypothesized that combination of long-term resistance exercise and IDON would improve markers of muscle mass and strength further compared with IDON alone . METHODS Thirty-two participants ( 21 male ; mean age , 43 ± 13 years ) on chronic hemodialysis were r and omly assigned to IDON plus resistance exercise ( NS + EX ) , or IDON ( NS ) alone for 6 months . IDON consisted of a lactose-free formula consisting of protein , carbohydrate , and fat . Three sets of 12 repetitions of leg-press were completed before each dialysis session in the NS + EX arm . Primary outcome measurement was lean body mass . Muscle strength and other nutritional parameters were measured as secondary outcomes . RESULTS Of 32 participants , 22 completed the 6-month intervention . There were no statistically significant differences between the study interventions with respect to changes in lean body mass and body weight , when comparing NS + EX to NS . There were also no statistically significant differences in any of the secondary outcomes measured in the study . Body weight ( 80.3 ± 16.6 kg , 81.1 ± 17.5 kg , and 80.9 ± 18.2 kg at baseline , month 3 , and month 6 , respectively ; P = .02 ) and 1-repetition maximum ( 468 ± 148 lb , 535 ± 144 lb , and 552 ± 142 lb , respectively ; P = .001 ) increased statistically significantly during the study for all patients combined . CONCLUSION This study did not show further benefits of additional resistance exercise on long-term somatic protein accretion above and beyond nutritional supplementation alone . When both treatments groups were combined , body weight and muscle strength improved during the study In previous beta-blocker trials , post-myocardial infa rct ion ( MI ) patients were essentially treated with a beta-blocker or placebo . In the CAPRICORN trial , patients were selected on the basis of a left ventricular ( LV ) ejection fraction ( EF ) < 40 % following the index MI and r and omised to carvedilol or placebo , in addition to modern secondary prophylaxis with ACE inhibitors , aspirin and statins . In 1959 patients with a mean LVEF of 33 % , treatment with carvedilol over a mean follow-up period of 15 months reduced total mortality from 15.3 % with placebo to 11.9 % with carvedilol [ relative risk reduction ( RRR ) = 23 % , absolute risk reduction ( ARR ) = 3.4 % ] . The incidence of recurrent MI was reduced from 5.8 to 2.3 % ( RRR 41 % , ARR 2.3 % ) . The number needed to treat ( NNT ) to prevent one death was 28 for the entire study period and 43 for 1 year of treatment . The results of the CAPRICORN trial are compared with three previous beta-blocker post-MI trials : the Gothenburg metoprolol trial ( GMT ) , the Norwegian timolol trial ( NTT ) and the beta-blocker heart attack trial ( BHAT ) . The RRRs for total mortality were 36 % in the GMT and NTT , and 27 % in BHAT . The respective NNTs for total mortality were 32 , 18 and 38 . NNT for 1 year of treatment was 25 in NTT and 80 in BHAT . The RRR for recurrent MIs were 28 % in NTT and 16 % in BHAT . The reduction of mortality and recurrent MIs in CAPRICORN is within the range of previous post-MI beta-blocker studies . In post-MI patients with LVEF<40 % , add-on treatment with a beta-blocker should be given > 48 h after initiation with an angiotensin-converting enzyme inhibitor ( ACEI ) and then with a slow dose escalation as applied in CAPRICORN INTRODUCTION We aim ed determine the impact of an 8-week intradialytic exercise program , consisting of 15 minutes of cumulative duration low-intensity exercise during the first 2 hours of dialysis on serum electrolytes levels and hemoglobin . MATERIAL S AND METHODS In a r and omized controlled trial of in an outpatient hemodialysis unit , clinical ly stable hemodialysis patients ( n = 47 ) were included and assigned into the aerobic exercise group ( n = 25 ) and the control group ( n = 23 ) . Aerobic exercises were done in groups , 15 min/d , 3 times a week , for 2 months . The main outcome measures were biochemical variables including serum levels of calcium , phosphate , and potassium levels and hemoglobin level . RESULTS After an 8-week intervention , significant improvements were seen in serum phosphate levels ( decreased by 1.84 mg/dL ) and serum potassium levels ( decreased by 0.69 mg/dL ) . No side-effects were observed . Serum calcium and hemoglobin levels did not change significantly in the exercise group . CONCLUSIONS A simplified aerobic exercise program is a complementary , safe , and effective clinical treatment modality in patients with end-stage renal disease on dialysis Cardiovascular ( CV ) disease is the most common cause of mortality in end‐stage kidney disease ( ESKD ) , and arterial stiffness , measured by pulse wave velocity ( PWV ) , is an independent predictor of all‐cause and CV mortality . B‐type natriuretic peptide ( BNP ) levels are high in patients with CV disease and ESKD , and increases in BNP may also be a marker of CV risk . Regular exercise has many benefits on quality of life and physical strength and may also improve CV risk , but few studies have addressed the impact of exercise on CV risk in ESKD . We performed a prospect i ve cross‐over trial in 19 hemodialysis ( HD ) patients to assess the impact of regular exercise on surrogate markers of CV risk‐arterial compliance and BNP levels . Exercise involved the use of a bicycle ergometer for minimum 30 min at each HD session for 3 months , with a 1‐month washout period . Group A ( n=9 ) exercised for the first 3 months only , while group B ( n=10 ) performed no intradialytic exercise initially and exercised for 3 months at cross‐over ( month 4 ) . Pulse wave velocity was performed using a SphygmoCor device , with concurrent measurements of BNP and other serum markers , at the commencement of the study , at 3 months , and on completion . The mean PWV ( A : 10.4±3.1 m/s , B : 9.8±3.8 at baseline ) showed a trend toward improvement with exercise ( A : 8.7±2.7 , p=0.07 ) , and no significant change without ( B : 10.5±3.6 , p=0.31 ) . After cross‐over , there was an increase in PWV in group A with cessation of exercise ( 9.75±2.4 , p=0.01 vs. 3 months ) and an improvement in group B with exercise ( 9.33±2.3 , p=0.11 vs. 3 months ) . When comparing PWV after 3 months of exercise vs. 3 months of no exercise ( paired t test ) , there was a significant difference in favor of exercise ( 9.04±0.59 vs. 10.16±0.74 , p=0.008 ) . The mean BNP levels following 3 months of exercise were also lower than those after 3 months of no exercise ( 504.4±101.2 vs. 809.4±196.1[N<100 ] , p=0.047 ) . There was an overall improvement in PWV , and to a lesser extent BNP levels , with 3 months of intradialytic exercise compared with no exercise , suggesting that regular exercise in ESKD may be associated with improvements in arterial compliance and a reduction in CV risk Rational : Patients under regular dialysis can also present alterations in the cardiovascular , musculoskeletal , and metabolic systems . Objectives : The aim of this study is to compare the effects of strength and aerobic exercises performed during hemodialysis ( HD ) in individuals with chronic renal disease . Material s and Methods : R and omized clinical trial . It was developed as a program of exercises three times a week , in the first 2 h of HD for 8 weeks . The patients were divided into three groups : control ( Group 1 , n : 11 ) , strength ( Group 2 , n : 11 ) , and aerobic ( Group 3 , n : 10 ) . G1 has not developed any type of physical training ; G2 utilized a training load of 40 % of one repetition maximum ( 1RM ) with anklets , and developed three series of 15 repetitions . G3 pedaled seated in the dialysis seat , during 20 min , in an ergometric bicycle , with intensity regulated by the perceived effort scale . Before and after 8 weeks , the following variables were evaluated : respiratory muscular strength , pulmonary function , functional capacity , blood biochemistry , and quality of life . Main Findings : In the pre- and post-training comparison , there was statistically significant improvement ( p < 0.05 ) in the maximal inspiratory pressure ( MIP ) , number of steps achieved ( NSA ) , and quality of life ( QoL ) in the trained groups , as compared to the non-exercised group ( G1 ) . Conclusions : The strength and aerobic exercises developed during HD can improve the respiratory muscular strength , functional performance , and quality of life , when compared to individuals presenting the disease who have not developed any type of physical training Background Restless Legs Syndrome is very common in hemodialysis patients however there are no comparative studies assessing the effectiveness of a non-pharmacological treatment to a classical treatment on parameters related to syndromes ’ severity and quality of life . Methods In this r and omized , partially double blind , placebo controlled trial , thirty two hemodialysis patients with restless legs syndrome were r and omly assigned into three groups : 1 ) the exercise training group ( N = 16 ) , 2 ) the dopamine agonists group ( ropinirole 0.25 mg/d ) ( N = 8) and 3 ) the placebo group ( N = 8) . The intervention programs lasted 6 months . Restless Legs Syndrome severity was assessed using the international severity scale , physical performance by a battery of tests , muscle size and composition by computed tomography , body composition by Dual Energy X Ray Absorptiometry , while depression score , sleep quality , daily sleepiness and quality of life were assessed through question naires . Results Exercise training and dopamine agonists were effective in reducing syndrome ’s symptoms by 46 % ( P = 0.009 ) and 54 % ( P = 0.001 ) respectively . Within group changes revealed that both approaches significantly improved quality of life ( P < 0.05 ) , however , only the dopamine agonists significantly improved sleep quality ( P = 0.009 ) . Within group changes showed a tendency for lean body mass improvements with dopamine agonists , this reached statistical significance only with the exercise training ( P = 0.014 ) , which also reduced fat infiltration in muscles ( P = 0.044 ) and improved physical performance ( P > 0.05 ) in various tests . Between group changes detect significant improvements with both exercise and dopamine agonists in depression score ( P = 0.003 ) , while only the dopamine agonist treatment was able to significantly improve sleep quality , compared to exercise and placebo ( P = 0.016 ) . Conclusions A 6-month exercise training regime was as effective as a 6-month low dosage dopamine agonist treatment in reducing restless legs syndrome symptoms and improving depression score in uremic patients . Further research is needed in order to show whether a combination treatment could be more beneficial for the amelioration of RLS.Trial registration BACKGROUND Individuals with end-stage renal disease on hemodialysis therapy have reduced aerobic exercise capacity and reduced muscle strength . METHODS This was a single-blind , r and omized , placebo-controlled trial of an exercise intervention in hemodialysis patients administered erythropoietin . The intervention consisted of progressive resisted isotonic quadriceps and hamstrings exercise and training on a cycle ergometer three times weekly for 12 weeks . Individuals in the control group underwent a nonprogressive program of range-of-motion exercises . Both groups were observed for an additional 5 months without intervention . Outcomes were assessed without knowledge of treatment assignment at baseline , 12 weeks , and 5 months . A healthy age- and sex-matched sample provided comparative data . RESULTS Our sample was relatively high functioning , with a mean score on the Physical Function subscale of the Short Form 36 ( SF-36 ) of 76 of 100 . At 12 weeks , there were large and statistically significant differences in favor of the experimental group on the submaximal exercise test ( 14 W ; 95 % confidence interval , 2 to 26 ) and muscle strength ( 45 lb ; 95 % confidence interval , 9 to 81 ) , but not in the 6-minute walk , symptoms question naire , or SF-36 . Differences between the intervention and control groups at 12 weeks were not evident on retesting 5 months after the end of the intervention . Compared with the healthy sample , patients were significantly lower functioning on the submaximal exercise test , muscle strength , and 6-minute walk test at baseline . CONCLUSION In this high-functioning sample , the exercise program improved physical impairment measures , but had no effect on symptoms or health-related quality of life . The impact on patients with a greater degree of physical dysfunction needs to be rigorously studied Background . Significant health benefits result from regular physical activity , many which are important for transplant recipients . Although exercise capacity improves initially after transplant , it is not normalized , and only two studies have reported the effects of exercise training in this population . We report a r and omized clinical trial of exercise after renal transplantation ( RTX ) . Methods . One hundred sixty-seven patients were r and omized at 1 month after RTX into two groups : exercise intervention ( EX ) and usual care ( UC ) , with repeat testing at 6 and 12 months . Ninety-five patients completed the following testing at both testing times : symptom-limited treadmill testing with measurement of peak oxygen uptake ( peak < & OV0312;>Vo2 ) ; isokinetic muscle testing for muscle strength ; and dual-energy X-ray absorptiometry scans for body composition . The SF-36 Health Status Question naire assessed self-reported functioning . The exercise intervention consisted of individually prescribed programs to be conducted at home with regular phone follow-up to enhance adherence . Repeated measures analysis of variance was performed to determine differences between the groups for the three testing times . Results . At 1 year 67 % of the EX group were exercising regularly compared with 36 % of the UC group ( P = 0.01 ) . Compared with the UC group , the EX group had significantly greater gains in peak < & OV0312;>Vo2 ( P = 0.016 ) , percent age-predicted < & OV0312;>Vo2 ( P = 0.03 ) , and muscle strength ( P = 0.05 ) , and a trend toward higher self-reported physical functioning ( P = 0.06 ) . There were no differences between the groups in changes in body composition . At 1 year , peak < & OV0312;>Vo2 was significantly correlated with age , percent fat , muscle strength , hematocrit , and self-reported physical functioning . Conclusions . Exercise training after RTX results in higher levels of measured and self-reported physical functioning ; however , exercise alone does not affect body composition AIMS The objective of this study was to determine whether 24 weeks resistance training during hemodialysis could improve exercise capacity , muscle strength , physical functioning and health-related quality of life compared to a low intensity aerobic program . MATERIAL AND METHODS 27 patients ( 55.6 + /- 17.6 years ) were recruited from two hemodialysis clinics in Valencia ( Spain ) . Patients were r and omized to resistance training ( n = 19 ) or low-intensity aerobic training ( n = 8) . Resistance training consisted of three sets of 4 exercises at an intensity of 12 - 15 out of 20 at the rate of perceived exertion scale ( Borg scale measuring self-rated exercise intensity ) using weights and elastic b and s on every session during 24 weeks . Primary outcomes included physical performance tests , evaluated by the " sit-to-st and -to-sit tests " and the 6 minutes walking test , and knee extensor muscles strength , evaluated by isometric dynamometry . Secondary outcomes included cardiorespiratory fitness , measured by time and METs ( measure of energy expenditure as ml of oxygen per kg of weight and per minute ; 1 MET is equal to 3.5 ml O(2)/kg/min ) achieved on a grade d exercise test , and quality of life , measured by the SF-36 question naire . RESULTS No differences were noted in change-over-time between the two groups in any of the physical performance tests . However , a significant change was found in change-over-time in right knee extensor muscles dynamometry , and intragroup analysis showed a significant improvement in resistance training groups in the physical performance tests and METs . CONCLUSIONS These findings suggest that resistance training during hemodialysis improves patient 's physical functioning BACKGROUND Systemic inflammation and protein-energy malnutrition may be associated with poor outcomes in kidney disease . METHODS We studied 26 adults ( age , 65 + /- 10 [ SD ] years ) with chronic kidney disease , not on dialysis therapy . Subjects were r and omly assigned to resistance training ( n = 14 ) or a control group ( n = 12 ) for 12 weeks , while counseled to consume a low-protein diet ( protein , approximately 0.6 g/kg/d ) . We determined whether resistance training reduces levels of inflammatory mediators ( serum C-reactive protein [ CRP ] and interleukin-6 [ IL-6 ] ) , in addition to previously reported improvements in nutritional and functional status in this same subject population . RESULTS Serum CRP levels were reduced in subjects undergoing resistance training ( -1.7 mg/L ) compared with controls ( 1.5 mg/L ; P = 0.05 ) . Similarly , IL-6 levels were reduced in the resistance-exercise group versus controls ( -4.2 versus 2.3 pg/mL ; P = 0.01 ) . Resistance training lead to skeletal muscle hypertrophy , shown by increases in type I ( 24 % + /- 31 % ) and type II ( 22 % + /- 41 % ) muscle fiber cross-sectional areas , compared with control subjects ( -14 % + /- 34 % and -13 % + /- 18 % , respectively ; P < 0.05 ) . Muscle strength also improved with resistance training ( 28 % + /- 14 % ) compared with controls ( -13 % + /- 22 % ; P = 0.001 ) . CONCLUSION Resistance training reduced inflammation and improved nutritional status in individuals with moderate chronic kidney disease consuming a low-protein diet . These results need to be investigated further in larger cohorts of patients with varying stages of kidney disease to determine whether resistance training can improve disease outcomes long term Hemodialyzed ( HD ) patients with end-stage renal disease ( ESRD ) exhibit lower fitness as a consequence of chronic uremic changes that trigger various structural , metabolic , and functional abnormalities in skeletal muscles . The aim of this r and omized study was to compare the effect of rehabilitation ( RHB ) training on a bicycle ergometer and electromyostimulation ( EMS ) of leg extensors in HD patients with ESRD . Thirty-two HD patients ( 18 men/14 women ; mean age 61.1 ± 8.8 years ) were r and omized into three groups : ( i ) exercise training ( ET ; n = 11 ) on bicycle ergometer 2 × 20 min ; ( ii ) EMS ( n = 11 ) where stimulation ( 10 Hz ) of leg extensors was applied for 60 min ; and ( iii ) controls ( CON ; n = 10 ) without exercise . Exercising was performed between the 2nd and the 3rd hour of HD , three times a week , 20 weeks in total . Ergometric test was performed in order to evaluate peak workload ( W(peak ) ) , 6-min corridor walking test ( CWT ) to evaluate the distance walked , and dynamometry of leg extensors to assess muscle power ( F(max ) ) . Urea clearance was monitored and expressed as st and ard parameters : spKt/V , spKt/V equilibrated ( spKt/V-e ) , and the urea removal ratio ( URR ) . Quality of life ( QoL ) was assessed by the question naire SF-36 . A significant increase of F(max ) ( P = 0.040 in group ET ; P = 0.032 in group EMS ) , of 6-min CWT ( P < 0.001 in ET group ; P = 0.042 in EMS group ) , and of W(peak ) ( P = 0.041 in ET group ) was observed . In both exercising groups , significant increase of spKt/V , spKt/V-e , and URR was found as compared with initial values ( P < 0.05 ) . In both exercising groups , highly significant changes in summarized mental functions were found ( P = 0.001 ) ; in summarized physical components , significant improvement was observed in the ET group ( P = 0.006 ) . Intradialytic RHB showed comparable positive effects on functional parameters , urea clearance , and QoL. Intradialytic EMS might represent wide therapeutic possibility in the near future BACKGROUND AND PURPOSE This study aims to compare the effects of combined resistance and aerobic exercise with a resistance programme alone on functional performance among haemodialysis patients . DESIGN The design was a r and omized controlled trial . SETTING The setting was the dialysis unit of a Brazilian university hospital . PATIENTS Haemodialysis patients were assigned to one kind of intervention or another . INTERVENTION The patients were assigned to receive the resistance exercise combined with an aerobic training or to maintain an ongoing resistance programme alone for a period of 10 weeks . MAIN OUTCOME MEASURE The functional performance of patients was assessed before and after the intervention through the 6-minute walk test ( 6MWT ) . The difference over time of the 6MWT was compared between the groups through two-way repeated- measures ANOVA . RESULTS Thirteen patients were allocated for each group of intervention . The difference in distance walked before and after intervention in the combined training group was of + 39.7 ± 61.4 m , and the difference in the resistance training group was of -19.2 ± 53.9 m , p = 0.02 . CONCLUSIONS Although the best protocol of exercise for patients on dialysis is not yet clear , in our sample of haemodialysis patients the combination of aerobic and resistance training was more effective than resistance training alone to improve functional performance Advances in medical treatment have improved the rehabilitation potential of predialysis ( P ) and dialysis ( D ) patients , but deficits remain in their physical and vocational functioning . We studied 18 P ( expected to begin dialysis in 6–12 months ) and 18 D patients ( on dialysis 1–5 years ) for 1 year . Exercise coaching and rehabilitation counseling were provided at no cost for the first 6 months to half of each patient group ( rehabilitation group = R ) ; the other half were assigned r and omly to controls ( C ) . No R services were provided during 6 months of follow-up . PR walked further in 6 min at 6 months ( + 3.9 m ) and 12 months ( + 4.1 m ) than initially ( p < 0.01 ) . Hematocrit increased in R ( p < 0.05 ) , but not in C. Symptom scores were stable in D , worsened 21 % in PC , and improved 15 % in PR . Sickness impact profile scores were better in PR than PC at 6 months ( p < 0.05 ) and 12 months ( NS ) . Comorbidity correlated with symptoms ( r = + 0.34 , p < 0.05 ) , self-rated affect ( r = –0.35 , p < 0.05 ) , and self-rated Karnofsky index of disability ( r = –0.37 , p < 0.05 ) , but not with physician-rated affect or physician-rated Karnofsky index of disability . Thus , quality of life was stable or improved in PR , but declined in PC ; PR benefited more than DR . Rehabilitation services are more beneficial before than after patients stabilize on dialysis , and quality of life monitoring should continue indefinitely Exercise training has well documented beneficial effects in a variety of cardiac disorders . End stage renal disease patients present many cardiovascular complications and suffer from impaired exercise capacity . No study to date has adequately examined the cardiac responses to exercise training in renal patients on hemodialysis ( HD ) . To determine the effects of an exercise rehabilitation program on the left ventricular function at rest and during submaximal effort , 38 end-stage renal disease patients on maintenance HD were r and omised into three groups . Sixteen of them ( group A -- mean age 46.4+/-13.9 years ) , without clinical features of heart failure , participated in a 6-month supervised exercise renal rehabilitation program consisting of three weekly sessions of aerobic training , 10 ( group B -- mean age 51.4+/-12.5 years ) followed a moderate exercise program at home , and the other 12 ( group C -- mean age 50.2+/-7.9 years ) were not trained and remained as controls . The level of anemia and the HD prescription remained constant during the study . Fifteen sex- and age-matched sedentary individuals ( group D -- mean age 46.9+/-6.4 years ) were the healthy controls . All subjects at the start and end of the program underwent physical examination , laboratory tests , treadmill exercise testing , M-mode and 2-D echocardiograms performed at rest and at peak of supine bicycle exercise . Left ventricular volumes ( EDV , ESV ) and mass ( LVM ) were measured and ejection fraction ( EF ) , stroke volume index ( SVI ) and cardiac output index ( COI ) were calculated by st and ard formulae . The maximal oxygen consumption increased by 43 % ( P<0.001 ) and the exercise time by 33 % ( P<0.001 ) after training in group A , by 17 % ( P<0.001 ) and 14 % ( P<0.01 ) , respectively , in B , and both remained unchanged in group C. Training in group A was also associated with an increase in LVIDd ( from 52.1+/-6.4 to 54.0+/-6.1 mm , P<0.001 ) and LVM ( 226+/-67 to 240+/-84 g , P<0.05 ) at rest with no change noted in groups B and C. Following a 6-month exercise training in group A an increase was also found in the resting EF by 5 % ( P<0.01 ) and SVI by 14 % ( P<0.001 ) . There was no change found in groups B and C. Supine bicycle exercise after training in group A was associated with an improvement in EF by 14 % compared to the pre-training change ( P<0.001 ) , SVI by 14 % ( P<0.001 ) and COI by 73 % ( P<0.001 ) . These changes from rest to submaximal exercise were less pronounced in group B following training at home . The untrained patients demonstrated no changes in LV systolic function over the 6-month period . These results demonstrate that intense exercise training improves LV systolic function at rest in HD patients ; both intense and moderate physical training leads to enhanced cardiac performance during supine submaximal exercise Chronic renal insufficiency , regardless of cause , generally progresses to end-stage renal disease ( 1 ) . Malnutrition and muscle wasting in chronic uremia often parallel the progression of renal failure ( 2 ) . They also contribute to excess morbidity and mortality in patients with renal disease ( 3 ) . Protein-restricted diets delay the progression of renal disease ( 4 , 5 ) and alleviate uremic symptoms ( 6 ) . Although nutritional status , as assessed by biochemical and anthropometric indicators , may be maintained during protein restriction ( 6 , 7 ) , studies have shown that deterioration of nutritional status is associated with low energy and protein intake in patients with chronic renal insufficiency ( 8) . Resistance training increases nitrogen retention ( 9 ) , protein synthesis ( 10 ) , and expression of insulin-like growth factor I in skeletal muscle ( 11 ) ; ameliorates losses of muscle mass and function ; and enhances quality of life ( 12 ) in both healthy and unwell persons . The anabolic potential of resistance training counteracts the catabolism of HIV infection ( 13 ) and myopathy secondary to corticosteroid use in cardiac transplantation ( 14 ) , the loss of lean tissue during energy restriction for obesity ( 15 ) , and the interleukin-mediated myopathy of chronic heart failure ( 16 ) . However , its utility as an adjunctive treatment off setting the catabolism of a low-protein diet in uremic patients is not known ( 17 ) . We conducted a r and omized , controlled trial to determine whether resistance training would preserve lean body mass , nutritional status , and muscle function through alterations in protein turnover ( synthesis and oxidation ) in patients with moderate chronic renal insufficiency who were consuming a low-protein diet to slow the progression of renal failure . Methods Study Design Patients older than 50 years of age with chronic renal insufficiency were r and omly assigned to a low-protein diet plus resistance training or a low-protein diet plus sham exercises ( referred to as low-protein diet alone ) . Patients were asked to follow a low-protein diet ( 0.6 g/kg of body weight per day ) for 2 to 8 weeks ( run-in period ) before r and omization . They continued the low-protein diet for an additional 12 weeks after r and omization ( intervention period ) ( Figure 1 ) . The Human Investigation Review Committee at Tufts University , Boston , Massachusetts , and collaborating hospitals approved the study , and written informed consent was obtained from all patients . Figure 1 . Flow of patients through the study . * The post office returned letters because addresses were incorrect or persons had relocated . No patients withdrew , experienced ineffective interventions , or were lost to follow-up . One patient in each group had incomplete postintervention measures because of health-related reasons . HNRCA = Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging . Study Sample Patients were recruited from the nephrology clinic at New Engl and Medical Center , Saint Elizabeth 's and Newton Wellesley Hospitals , and the Lahey Hitchcock Clinic , all in Boston , Massachusetts . Screening procedures took place at the Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging ( HNRCA ) at Tufts University . These procedures included sociodemographic and health history question naires ; physical examination ; electrocardiography ; blood hematology , chemistry , and urine analyses ; and a treadmill stress test . Eligibility criteria included serum creatinine concentrations between 133 and 442 mol/L ( 1.5 and 5.0 mg/dL ) and physician approval to follow a low-protein diet . A nephrologist confirmed renal diagnosis by review ing renal biochemistry results and clinical records . Exclusion criteria were myocardial infa rct ion ( within the past 6 months ) , any unstable chronic condition , dementia , alcoholism , dialysis or previous renal transplantation , current resistance training , recent involuntary weight change ( 2 kg ) , albumin level less than 30 g/L , proteinuria greater than 10 g/d , or abnormal stress test results at screening ( 18 ) . Reasons for early withdrawal from the study included loss of more than 25 % of initial body weight ; need for dialysis or transplantation ; development of any serious condition requiring hospitalization or precluding exercise ; and signs of malnutrition , such as a decrease in serum transferrin levels to less than 1.5 g/L or a 15 % decrease in hemoglobin or leukocyte count to below baseline levels . Diet Dietary intake of macronutrients and micronutrients and adherence to the low-protein diet were monitored twice per week during the run-in period and weekly during the intervention period by 3-day assisted dietary records ( including week and weekend days ) and regular meetings with the study dietitian , who was not blinded to group assignment . Dietary data were coded and analyzed by using Nutritionist-IV software ( N-Squared Computing , San Bruno , California ) . Patients collected one 24-hour urine specimen for every 3-day dietary record . Protein intake was also estimated by urea nitrogen levels ( 19 ) calculated from urine collection s and was used to assess adherence , which was defined as intake within 15 % of the prescribed low-protein intake ( 0.6 g/kg per day ) . Patients were counseled to reduce their habitual protein intake by eating food sources with less protein or by reducing portion sizes of higher-protein foods . Behavior modification strategies , including tips , recipes , food models , and self-monitoring tools for protein counts , were provided . These strategies were adapted from the Modification of Diet in Renal Disease Study ( 20 ) . Exercise Muscle strength was determined twice before r and omization and once after 12 weeks by measuring one repetition maximum ( 1 RM ) ( 21 ) using Keiser resistance training equipment ( Keiser Sports Health Equipment , Inc. , Fresno , California ) . One repetition maximum is the heaviest load that can be lifted once in good form through the full range of motion . Five machines ( chest and leg press , latissimus pull-down , knee extension , and knee flexion ) were used to include functionally large muscle groups . The better of the two baseline measurements of 1 RM was used in analyses and to set initial training loads for patients r and omly assigned to resistance training . All exercise sessions were performed at the HNRCA three times per week under the supervision of an exercise physiologist . Vital signs and body weight were recorded before each session . Patients who performed resistance training had monthly 1 RM testing on each machine . Workload during training was adjusted to reflect 80 % of the most recent 1 RM . In addition , patients ' workloads were progressively increased as appropriate according to the trainer 's objective perception of patients ' difficulty with workloads at each session . Patients performed three sets of eight repetitions on each machine per session , which lasted about 45 minutes ( 21 ) . Patients assigned to the low-protein diet alone performed five to eight sham exercises ( gentle movements while st and ing , sitting , and bending ) for the upper and lower body . These were design ed not to have a physiologic impact but to provide trainer contact time similar to that of the resistance training group . Study Measures All measures were taken before ( week 0 ) and 12 weeks after r and omization . Observers were blinded to study group assignment at all times , except during assessment s of postintervention muscle strength . Main Outcome Measures Total body potassium is the best single measure of body cell mass closely linked to functional status ( 22 ) , prognosis , and survival ( 23 ) . Body cell mass ( muscle and viscera ) comprises the metabolically active tissues where protein is targeted ( 24 ) . Potassium-40 represents approximately 0.0118 % of total body potassium . Loss of total body potassium occurs in patients following low-protein diets ( 25 ) and in patients with renal disease ( 26 ) , as well as in patients with many other wasting syndromes . Total body potassium was determined in the body composition laboratory at HNRCA , with a coefficient of variation of 5 % ( 24 ) . Regional body composition of the area involving the mid-thigh muscle was determined by computerized tomography of the nondominant thigh . A Siemens DR3 CT Scanner ( Somatom-Siemens , Erlangen , Germany ) was used to obtain an 8-mm scan at the midpoint between the inguinal crease and the proximal pole of the patella . Images were digitized and analyzed to the nearest 0.01 cm2 , as described elsewhere ( coefficient of variation , 0.5 % to 1.5 % ) ( 21 ) . Type I and type II muscle-fiber cross-sectional areas were determined from vastus lateralis muscle biopsies of the nondominant thigh , performed with a 5-mm Bergstrom needle ( 27 ) . Sections were stained with adenosine triphosphatase ( pH , 4.3 ) to visualize type I and type II fibers . A slide preparation was made for each biopsy specimen , and 50 to 150 fibers per patient were analyzed by light microscopy ( coefficient of variation , 3 % ) ( 11 , 27 ) . Anthropometry Body weights were measured to the nearest 0.1 kg on a Toledo Weight-Plate ( Bay State Scale & Systems , Inc. , Burlington , Massachusetts ) . Height was measured once to the nearest 0.25 cm , without shoes , by using a wall-mounted stadiometer . Body mass index was determined from body weight and height as kg/m2 . Biochemical Measures All measurements were collected in the fasting state in a blinded fashion at the nutrition evaluation laboratory at HNRCA ( coefficient of variation , 5 % to 10 % ) . Urea nitrogen and creatinine concentrations in serum and urine and levels of plasma insulin-like growth factor I were determined , as described elsewhere ( 25 , 27 ) . In addition , blood cell count ; hematocrit ; and levels of serum albumin , transferrin , and prealbumin were measured monthly to evaluate nutritional status . Glomerular Filtration Rate Glomerular filtration rate was measured as the renal clearance of 125I-iothalamate ( Glofil , Cypros Pharmaceutical Corp. , Carlsbad , California ) , with a coefficient of BACKGROUND Hemodialysis patients show reduced physical function and greater risk of increased arterial stiffness because of hypertension , metabolic disturbances , and vascular calcification . Exercise interventions potentially could improve their vascular risk profile . STUDY DESIGN R and omized controlled pilot clinical study comparing the effects of 6 months of supervised intradialytic exercise training versus home-based exercise training or usual care on physical function and arterial stiffness in hemodialysis patients . SETTING & PARTICIPANTS 70 hemodialysis patients from 3 renal units . INTERVENTION Intradialytic-exercise patients trained 3 times/wk for 6 months on a cycle ergometer and home-based-exercise patients followed a walking program to achieve the same weekly physical activity . Usual-care patients received no specific intervention . OUTCOMES & MEASUREMENTS Primary outcome measures were distance traveled during a 6-minute walk test and aortic pulse wave velocity . Secondary outcome measures included augmentation index ( augmentation pressure as a percentage of central pulse pressure ) , peripheral ( brachial ) and central blood pressures ( measured noninvasively using radial tonometry ) , physical activity , and self-reported physical functioning . Measurements were made at baseline and 6 months . RESULTS At 6 months , there were no significant differences between changes in 6-minute walk test distance ( intradialytic exercise , + 14 % ; home-based exercise , + 11 % ; usual care , + 5 % ) , pulse wave velocity ( intradialytic exercise , -4 % ; home-based exercise , -2 % ; usual care , + 5 % ) , or any secondary outcome measure . LIMITATIONS Lack of medication data limited the analysis of vascular parameters in this study . CONCLUSION There were no differences between intradialytic or home-based exercise training and usual care for either physical function or vascular parameters OBJECTIVE To investigate if high-intensity constant work rate ( CWR ) would constitute a more appropriate testing strategy compared with incremental work rate ( IWR ) to assess the effectiveness of intradialytic aerobic training in patients with end-stage renal disease ( ESRD ) . DESIGN R and omized controlled trial . SETTING Nephrology unit at the university hospital . PARTICIPANTS Patients ( N=28 ; 47.0±11.9y ) under hemodialysis ( 4.4±4.3y ) were r and omly assigned to exercise and control groups . INTERVENTION Patients included in the exercise group underwent a moderate-intensity intradialytic aerobic training program 3 times per week for 12 weeks . MAIN OUTCOME MEASURES Cardiopulmonary and perceptual responses were obtained during an IWR and a high-intensity CWR test to the limit of tolerance on a cycle ergometer . RESULTS Training-induced increases in peak oxygen uptake ( Vo(2)peak ) and time to exercise intolerance ( Tlim ) . Mean improvement in Tlim ( 97.4%±75.6 % ) was significantly higher than increases in Vo(2)peak ( 12%±11.3 % ) ( P<.01 ) ; in fact , while Tlim improved 50 % to 200 % in 9 of 12 patients , Vo(2)peak increases were typically in the 15 % to 20 % range . CWR test revealed lower metabolic , ventilatory , cardiovascular , and subjective stresses at isotime ; in contrast , submaximal responses during the incremental work rate ( at the gas exchange threshold ) remained unaltered after training . CONCLUSIONS A laboratory-based measure of endurance exercise capacity ( high-intensity CWR test to Tlim ) was substantially more sensitive than oxygen uptake at the peak IWR test to unravel the physiologic benefits of an intradialytic aerobic training program in mildly impaired patients with ESRD BACKGROUND Multiple risk-factor interventions that include lifestyle changes have been proved to be effective in reducing risk profile in persons at high risk for developing coronary heart disease ( CHD ) . There have not been similar studies involving transplant recipients . The purpose of this study is to examine effects of exercise training on cardiovascular risk profile during the first year after renal transplantation . We used traditional CHD risk factors and the Framingham CHD prediction methods . METHODS Ninety-six transplant recipients were r and omly assigned to 2 groups at 1 month posttransplantation : the exercise training ( EX group ; n = 51 ) and usual care groups ( UC group ; n = 45 ) . Testing was performed at baseline and 12 months posttransplantation and included maximal exercise testing and evaluation of CHD risk factors and risk-factor categories , determined by means of the Framingham equations . RESULTS Overall 10-year CHD risk score did not change in either group . All patients showed increases in total cholesterol ( TC ) level , high-density lipoprotein fraction of cholesterol ( HDL-C ) , and body mass index over time . No differences were observed between groups , except for a trend toward greater improvement in HDL cholesterol levels in the EX group ( P = 0.07 ) . Significantly more patients in the EX group moved out of the high-risk category in TC-HDL ratio . All patients remained in the high-risk category for physical fitness . There was a significant negative correlation of CHD risk and maximal exercise capacity ( r = -0.406 ; P < 0.001 ) . CONCLUSION Exercise training alone does not reduce CHD risk during the first year after transplantation . Research to determine the effects of multiple risk interventions during a longer period in transplant recipients is warranted OBJECTIVE To determine if differences exist in kilocalorie and protein intake and visceral protein levels for patients with End-Stage Renal Disease ( ESRD ) exercising during dialysis versus not exercising . DESIGN Prospect i ve study of 11 patients with ESRD over a study period of 12 weeks . SETTING Outpatient renal dialysis clinic . PATIENTS Patients with ESRD undergoing hemodialysis ( HD ) three times weekly who met the following criteria were selected : aged 25 to 65 years , nondiabetic , no current physical activity , blood pressure of 160/95 mm Hg or less at the second hour of HD , no unstable angina pectoris . Eleven patients who met the criteria were r and omized into two groups ; five patients with exercise ( E ) and six patients without exercise ( NE ) . INTERVENTIONS From weeks 5 to 8 , E patients began exercise during HD three times a week . Exercise gradually increased by 3 minutes each dialysis day , maintaining 60 % to 80 % maximal heart rate ( HR ) . By the end of week 8 , all E patients reached 45 minutes of exercise , including 5 minutes each of warm-up and cooldown . Patients continued 45 minutes of exercise each dialysis day during HD at 60 % to 80 % maximal HR during weeks 9 through 12 . NE patients remained sedentary throughout the study . MAIN OUTCOME MEASURE Twenty-four-hour dietary recalls were obtained weekly for the 12 weeks from all patients for kilocalorie and protein intake . Serum levels of prealbumin , transferrin , and predialysis and postdialysis albumin were obtained immediately before the study onset and at weeks 4 , 8 , and 12 . Comments related to patients ' feelings and exercise were recorded but not analyzed statistically . RESULTS Analysis of covariance for repeated measures for kilocalories yielded no significance by group or over time . Mean intakes for E patients for weeks 9 through 12 were clinical ly greater than weeks 1 through 8 by approximately 200 kilocalories . The mean protein intake for E patients at weeks 9 through 12 ( 79 + /- 41 g ) appeared clinical ly greater than NE patients at weeks 9 through 12 ( 58 + /- 11 g ) , although not statistically different . Adequacy of dialysis ( Kt/V ) and initial levels of each serum protein were covariates for analysis of variance . No statistical differences were found for prealbumin levels . Transferrin levels were within normal ranges but differed ( P < .05 ) by group ( E or NE ) and time periods . Prealbumin and postalbumin concentrations ranged from slightly low to adequate levels and were different over time ( P < . 05 ) . CONCLUSION Kilocalorie and protein intakes appeared to increase for E patients during the exercise program . No consistent increases of visceral proteins were found for E patients . A majority of E patients expressed feelings of improved health , better exercise tolerance , and improved appetite and viewed exercise as enjoyable OBJECTIVE This study was conducted to determine the impact of an 8-week intradialytic exercise program ( consisting of 15 minutes low-intensity exercise during the first 2 hours of dialysis ) on dialysis efficacy . METHODS In an open r and omized controlled trial , a total of 50 clinical ly stable hemodialysis patients were enrolled into the study and r and omly allocated into two groups : the aerobic exercise group ( n=25 ) and the control group ( n=25 ) . Aerobic exercises were done in the intervention group for 15 min/day , three times a week for 2 months . The dialysis efficacy was assessed prior to and at the end of each month of the program . RESULTS The efficacy of dialysis increased at the end of the first month and remained elevated for the duration of the program in the exercise group ( p<0.05 ) . CONCLUSION A simplified aerobic exercise program has increased the efficacy of dialysis and may be considered as a safe , complementary and effective modality for hemodialysis patients Background : The number of chronic renal failure patients treated by hemodialysis ( HD ) is continuously increasing . Most patients have reduced physical capacity and have a high risk of cardiac and vascular diseases . The aim of this study was to determine the effects of 5 months physical exercise of HD patients ’ physical capacity , self-rated health and risk factors for cardiovascular disease . Methods : 33 HD patients were included in the study . Inclusion criteria : HD for more than 3 months , age > 18 years . Exclusion criteria : Diabetes mellitus , symptomatic cardiovascular disease , musculoskeletal limitations , severe peripheral polyneuropathy , inability to speak Danish or English , dementia or other mental disorders . The patients were r and omly assigned to an exercise group ( EG , n = 22 ) or a control group ( CG , n = 11 ) . Prior to r and omization , baseline testing was performed . The effects were measured by aerobic capacity , ‘ 2-min stair climbing ’ , ‘ squat test ’ , self-rated health ( SF36 ) , blood pressure and lipids . All tests were carried out by blinded testers . The intervention consisted of 1 h of physical exercise twice a week for 5 months . Results : 20 patients completed the intervention . Attendance was 74 % of all sessions . There were no dropouts caused by complications related to the intervention . The EG had a significant increase in aerobic capacity , ‘ squat test ’ and Physical Function and Physical Component Scale ( SF36 ) . No significant changes were observed in any of the parameters in the CG . Conclusion : Physical exercise twice a week for 5 months increases physical function and aerobic capacity in HD patients . An exercise program with only two exercise sessions per week seems easy to implement in clinical practice with high attendance among participants . Further investigation is needed to determine the effects on blood pressure and lipids . There were no medical complications related to the exercise program BACKGROUND Noninvasive screening studies may identify hemodialysis ( HD ) patients at increased risk of sudden cardiac death . Interventions that improve the findings of such screening studies may reduce sudden cardiac death . STUDY DESIGN R and omized and controlled clinical trial . SETTING & PARTICIPANTS 59 HD patients were r and omly assigned to an exercise training group ( group A ; 30 patients ) or control group ( group B ; 29 patients ) . INTERVENTION Group A participated in a 10-month supervised exercise training program during the HD sessions ( 3 times weekly ) . OUTCOMES Each risk factor separately and the composite risk score . Patients were considered high risk according to the criteria ( aerobic capacity : peak oxygen consumption [ Vo(2)peak ] < or = 14 mL/kg/min , left ventricular ejection fraction < or = 30 % , SD of normal RR intervals [ SDNN ] < or = 70 milliseconds , positive T-wave alternans , or positive late potentials ) . Statistical analysis included a 2-group comparison of change scores and analysis of covariance adjusting for baseline . MEASUREMENTS At entry and end of the study , Vo(2)peak and left ventricular ejection fraction were estimated , heart rate variability was calculated ( measurement of SDNN , mean RR intervals ) , and the ratio between low- ( LF ) to high-frequency ( HF ) components ( LF/HF ) and late potentials and T-wave alternans were detected . RESULTS Baseline measurements were similar between the 2 groups . At follow-up , 9 patients from group A and 20 from group B ( P = 0.003 ) were considered high risk . The change in number of risk markers over time was significantly different between groups ( -0.5 + /- 0.7 in group A versus 0.07 + /- 0.3 in group B ; P < 0.001 ) . Additionally , the change in Vo(2)peak over time was 3.5 + /- 3.2 in group A and -0.2 + /- 3.5 mL/kg/min in group B ( P < 0.001 ) , left ventricular ejection fractions were 3.4 % + /- 3.9 % and 0.2 % + /- 7.7 % ( P < 0.05 ) , SDNNs were 12.6 + /- 16.3 and -1.1 + /- 10.2 milliseconds ( P < 0.001 ) , and LF/HF ratios were 0.3 + /- 0.4 and -0.1 + /- 0.3 ( P < 0.001 ) , respectively . Change in numerical score of the signal-averaged electrocardiogram also was found to be statistically different ( P < 0.05 ) between groups . LIMITATIONS Clinical outcomes , including survival , were not assessed . CONCLUSIONS Exercise training improves aerobic capacity and ameliorates some indicators of risk of sudden cardiac death in HD patients BACKGROUND Arterial baroreflex sensitivity ( BRS ) evaluation has been increasingly used as an index of cardiac autonomic control . Cardiac autonomic dysfunction leading to depressed BRS has been associated with an increased risk of ventricular arrhythmias and sudden death in patients with chronic kidney disease ( CKD ) on hemodialysis ( HD ) . AIM The purpose of this study was to investigate the effects of an exercise training program during hemodialysis on BRS in CKD patients . PATIENTS AND METHODS 43 HD patients participated in the study . They were r and omly assigned into either a 7-month exercise training program during HD ( Group A : n=22 patients ) or a sedentary control group ( Group B : n=21 patients ) . Additionally , 20 sex- and age-matched sedentary individuals comprised a healthy control group ( Group C ) . All patients at the beginning and the end of the study underwent a tilt test for evaluation of BRS and an exercise testing with spiroergometric study for cardiorespiratory capacity estimation . The level of Hb , medications and the HD procedure remained stable during the study . RESULTS At baseline BRS was found to be reduced by 51.5 % ( p<0.05 ) and baroreflex effectiveness index ( BEI ) by 36.4 % ( p<0.05 ) in Group A compared with Group C. Initially , all HD patients had also significantly lower exercise time and VO2 peak than the healthy subjects . After training , Group A showed a significant improvement in BRS by 23.0 % ( p<0.05 ) , in BEI by 27.0 % ( p<0.05 ) , in event and ramp count by 35.0 % ( p<0.05 ) and 29.0 % ( p<0.05 ) , respectively as well as in VO2 peak by 22.4 % ( p<0.05 ) and in exercise time by 40.9 % ( p<0.05 ) . Significant correlations were found between BRS and METs ( r=0.476 , p<0.05 ) , BRS and VO2 peak ( r=0.443 , p<0.05 ) , BEI and METs ( r = 0.492 , p<0.05 ) , BEI and VO2 peak ( r=0.467 , p<0.05 ) , event count and VO2 peak ( r=0.715 , p<0.01 ) , event count and exercise time ( r=0.799 , p<0.01 ) , in Group A at the end of the study . CONCLUSIONS Our results indicate that HD patients had considerably reduced cardiorespiratory capacity and impaired cardiac BRS compared to healthy sedentary individuals . Importantly , exercise training during HD yielded a marked increase of the indices representing baroreflex activity in association to the improvement of their functional capacity Dysfunction of the cardiac autonomic nervous system is a known complication of end-stage renal disease . The objective of the study was to mainly investigate the effects of physical training on 24-hour vagal cardiac activity in dialysis patients . Sixty chronic uremic patients ( mean age 48 + /- 12 years ) on maintenance hemodialysis were studied . After initial evaluation , 30 patients ( group A ) were r and omly assigned to a 6-month exercise training program ( 3/week ) . The other 30 patients ( group B ) and 30 nonuremic sedentary persons ( group C ) remained untrained and were used as controls . Parasympathetic activity was assessed at the beginning and the end of the study noninvasively from 24-hour electrocardiographic ambulatory monitoring by calculating heart rate variability ( HRV ) . HRV index , mean NN interval , and st and ard deviation NN ( SDNN ) were measured according to the " triangular method . " At baseline HRV index , mean RR , SDNN , and aerobic capacity were significantly reduced in both hemodialysis groups compared with values in group C. Also , 40 % of all patients on hemodialysis and 16 % of group C had arrhythmias ( Lown class > II ) . Moreover , hemodialysis patients with a more depressed HRV index ( < 25 , n = 37 ) had a higher incidence of arrhythmias ( 60 % ) compared to those with HRV index > 25 ( p < 0.05 ) . Exercise training in group A significantly increased HRV index from 22 + /- 7 to 28 + /- 9 ( p < 0.05 ) and SDNN from 0.11 + /- 0.03 to 0.13 + /- 0.04 ( p < 0.05 ) . Furthermore , fewer patients continued to have an HRV index < 25 ( by 40 % ) and arrhythmias ( by 33 % ) compared with baseline data . Training was also associated with a significant improvement in fitness level , as assessed by maximal oxygen consumption ( by 41 % ; p < 0.05 ) and exercise testing duration ( by 33 % ; p < 0.05 ) . There was a significant correlation in HRV index and maximal oxygen consumption . No changes were observed in the control groups between baseline and follow-up data . Results demonstrate that physical training in hemodialysis patients augments cardiac vagal activity and decreases vulnerability to arrhythmias Physical function limitation is a common disorder in chronic hemodialysis ( HD ) patients , relating to increased morbidity and mortality . The aim of this study was to determine the effects of aerobic and resistance trainings on blood lipids and inflammation status in HD patients . Out of 30 volunteer males who had been undergoing conventional maintenance HD within an HD unit in Tehran , 21 subjects were enrolled . They were r and omly assigned into aerobic exercise group – resistance training group undergoing an 8-week intradialytic exercise program ( three times/week ) and control group ( n = 7 , each ) . Training program consisted of 10 - 30 min stationary cycling at an intensity of 12–16 out of 20 at the rate of perceived exertion ( RPE ) of Borg scale in aerobic group and using ankle weights for knee extension , hip abduction and flexions at an intensity of 15–17 out of 20 at the RPE of Borg scale in resistance group . Fasting blood sample s for serum biochemistry were drawn at baseline and 8 weeks . The age , HD duration , and physical activity score were 51.6±18.9yrs ; 25.1±13.9 mo , and 19.2±7.6 , respectively . Diabetes mellitus ( 43 % ) , hypertension ( 28 % ) , and obstructive uropathy ( 14 % ) were the most common underlying diseases . Aerobic and resistance exercises were correlated with serum creatinine ( P < 0.0001 and P<0.001 ) and hs-CRP levels ( P=0.005 and P=0.036 ) reduction so that aerobic exercise induced more reduction . These exercises had no influence on weight , Kt/V values , serum urea , albumin , hemoglobin , and lipid levels ( P>0.05 ) . Both intradialytic aerobic and resistance exercises showed beneficial effects on inflammation status without any influences on serum lipid levels probably due to short duration of the study which was not accompanied with body weight changes . Solute removal had no change during exercise programs . There is a need for more investigation on the role of exercise in HD patients Functional capacity of end-stage renal disease patients is dramatically impaired . Although exercise training programs appear to have beneficial morphological , functional and psychosocial effects in end-stage renal disease patients on hemodialysis ( HD ) , the adherence rate is high . The purpose of this study was to compare the effects of three modes of exercise training on aerobic capacity and to identify the most favourable , efficient and preferable to patients on HD with regard to functional improvements and participation rate in the programs . Fifty-eight volunteer patients were screened for low-risk status and selected from the dialysis population . The 48 patients who completed the study protocol were r and omly assigned either to one of the three training groups or to a control group . Sixteen of them ( Group A - mean age 46.4+/-13.9 years ) completed a 6-month supervised outpatient exercise renal rehabilitation program consisting of three weekly sessions of aerobic and strengthening training on the non-dialysis days ; 10 ( Group B - mean age 48.3+/-12.1 years ) completed a 6-month exercise program during HD ; 10 ( Group C - mean age 51.4+/-12.5 years ) followed an unsupervised moderate exercise program at home , and 12 patients ( Group D-mean age 50.2+/-7.9 years ) were used as patient controls . The level of anemia , the medications and the HD prescription remained stable during the study . Fifteen sex- and age-matched sedentary individuals ( Group E - mean age 46.9+/-6.4 years ) comprised a healthy control group for baseline data . All subjects at the beginning and end of the study underwent clinical examination , laboratory tests and a treadmill exercise test to fatigue endpoints with direct measurement of aerobic capacity . Group A had a higher dropout rate ( 24 % ) compared to groups B ( 17 % ) and C ( 17 % ) . Peak oxygen consumption ( VO2 peak ) increased by 43 % ( p < 0.05 ) , anaerobic threshold ( VO2AT ) by 37 % ( p < 0.05 ) and exercise time by 33 % ( p < 0.05 ) after training in Group A ; by 24 % ( p < 0.05 ) , 18 % ( p < 0.05 ) and 22 % ( p < 0.05 ) , respectively , in B ; and by 17 % ( p < 0.05 ) , 8 % ( p < 0.05 ) and 14 % ( p < 0.05 ) , respectively , in C ; while both remained almost unchanged in Group D. These results demonstrate that intense exercise training on non-dialysis days is the most effective way of training , whereas exercise during HD is also effective and preferable The limitation to exercise capacity in hemodialysis patients has been attributed to anemia . We report the effects of normalization of hematocrit levels by using r-hu-recombinant erythropoietin and exercise training on exercise capacity and self-reported physical functioning in hemodialysis patients . Sixty-five patients were r and omized into 1 of 4 groups : usual hematocrit ( 30%-33 % ) with no exercise training ( UH ) ; usual hematocrit ( 30%-33 % ) plus exercise training ( UHX ) ; normalized hematocrit ( 40%-42 % ) with no exercise training ( NH ) ; and normalized hematocrit ( 40%-42 % ) plus exercise training ( NHX ) . Treadmill exercise testing was conducted at baseline and at 5 months after the initiation of the interventions . Analysis was performed on the data collapsed for 48 patients who met the criteria for hematocrit and exercise adherence and completed both baseline and post intervention ( 5.6 + /- 1.6 months ) testing . Significant effects of exercise were found in peak oxygen uptake measurements ( P = 0.03 ) and in self-reported physical functioning as measured by the Short Form-36 question naire ( P = 0.01 ) . There was a significant effect of hematocrit on the General Health scale on the SF-36 ( P = 0.03 ) . The changes in peak oxygen uptake with exercise training were small and levels remained lower than age-predicted values at the end of the study . These results indicate that there are other physiologic limitations to exercise capacity that are not overcome by exercise training or normalization of hematocrit . The effects of exercise training on self-reported physical functioning may be of clinical importance because these scores have been shown to be highly predictive of outcomes such as hospitalizations and mortality in hemodialysis patients INTRODUCTION Decreased heart rate variability ( HRV ) in patients with end stage renal disease ( ESRD ) undergoing hemodialysis is predictive of cardiac death , especially due to sudden death . OBJECTIVE To evaluate the effects of aerobic training during hemodialysis on HRV and left ventricular function in ESRD patients . METHODS Twenty two patients were r and omized into two groups : exercise ( n = 11 ; 49.6 ± 10.6 years ; 4 men ) and control ( n = 11 ; 43.5 ± 12.8 ; 4 men ) . Patients assigned to the exercise group were su bmi tted to aerobic training , performed during the first two hours of hemodialysis , three times weekly , for 12 weeks . HRV and left ventricular function were assessed by 24 hours Holter monitoring and echocardiography , respectively . RESULTS After 12 weeks of protocol , no significant differences were observed in time and frequency domains measures of HRV in both groups . The ejection fraction improved non-significantly in exercise group ( 67.5 ± 12.6 % vs. 70.4 ± 12 % ) and decreased non-significantly in control group ( 73.6 ± 8.4 % vs. 71.4 ± 7.6 % ) . CONCLUSION A 12-week aerobic training program performed during hemodialysis did not modify HRV and did not significantly improve the left ventricular function AIM We wished to determine if an 8-week program of exercise during dialysis in end-stage renal disease ( ESRD ) patients would increase urea removal ( enhance dialysis efficacy ) with subsequent improvements in work performance and perception of quality of life , and /or alterations in cardiovascular status . METHODS Self-care hemodialysis patients ( EX , n = 6 ) performed cycle ergometry exercise 3 times per week during their dialysis session at 40 - 50 % maximal work capacity for 15 min during each of the first 3 hours of dialysis and were matched for age , protein catabolism rate , and WLmax with a CON group ( n = 7 ) . Dialysis efficacy was measured using serum urea clearance ( Kt/V ) and dialysate urea clearance ( DUC ) during the first 2 hours of dialysis . Resting blood pressure was monitored on a sessional basis , pre- and postdialysis and during exercise in the EX group . QOL , measured using the SF-36 question naire , and WLmax were determined prior to and at 4 and 8 weeks of the exercise program . RESULTS DUC was significantly elevated in the EX group at the end of the exercise program , but was of insufficient magnitude to result in an overall increase in Kt/V. DUC decreased in the CON group but Kt/V remained unchanged . No changes in resting blood pressure occurred in either group over the course of the study , however , pulse pressure tended to increase in the CON group but decrease in the EX group , indicating a potential beneficial adaptation of the cardiovascular system in patients undergoing an exercise program . The exercise program had no effect on QOL scores and this was most likely due to the short duration of the exercise program and high-functioning level of the population studied as compared to normative data for this patient population . We also found that 33 % of the exercise sessions in the 3rd hour of dialysis were not performed due to hypotensive events . CONCLUSION Exercise during dialysis enhanced dialysate urea removal but not serum urea clearance . Alterations in the modality and the timing of exercise during dialysis may be required to elicit increases in serum urea clearance . It is also recommended that exercise during dialysis be performed during the first 2 hours of dialysis The aim was to assess the effects of exercise training on aerobic and functional capacity of patients with end‐stage renal disease ( ESRD ) . Patients completed an incremental exercise test on a cycle ergometer to determine VO2 peak and VO2 at ventilatory threshold ( VT ; V‐slope ) . On a separate day they performed two constant load exercise tests on a cycle ergometer at 90 % of VT and at a workload of 33 W , to determine VO2 kinetics . Functional capacity was assessed using measurements of sit‐to‐st and s ( STS‐5 , STS‐60 ) and a walk test . Dialysis patients were r and omly allocated to an exercise ( ET : n=18 , age=57·3 years ) or control ( C : n=15 , age=50·5 years ) group . The ET group participated in an exercise training programme involving cycling for 3 months . Repeated measures ANOVA revealed significant time by group interactions ( P < 0·05 ) following training for VO2 peak ( ET : 17 ± 6·1 versus 19·9 ± 6·3 , C : 19·5 ± 4·7 versus 18·8 ± 4·9 ml kg min–1 ) and VO2–VT ( ET : 10·7 ± 3·5 versus 11·8 ± 3·3 , C:12·9 ± 3·2 versus 11·9 ± 3·5 ml kg min–1 ) . VO2 kinetics remained unchanged in both groups at 90 % ‐VT , but a trend ( P=0·059 ) towards faster kinetics at the 33 W was observed ( ET : 49·6 ± 19·5 versus 37·8 ± 12·7 , C : 42·8 ± 13 versus 49·4 ± 20·2 s ) . Significant time by group interactions ( P < 0·05 ) were also observed for STS‐5 ( ET : 14·7 ± 6·2 versus 11·0 ± 3·3 , C : 12·8 ± 4·4 versus 12·7 ± 4·8 s ) and STS‐60 measurements ( ET : 21·2 ± 7·2 versus 26·9 ± 6·2 , C : 23·7 ± 6·8 versus 24·1 ± 7·2 ) . Three months of exercise rehabilitation significantly improves peak exercise capacity of patients with ESRD . Measurements of VO2 kinetics and functional capacity suggest that longer time might be needed to induce peripheral adaptations Patients who are on hemodialysis commonly experience muscle wasting and weakness , which have a negative effect on physical functioning and quality of life . The objective of this study was to determine whether anabolic steroid administration and resistance exercise training induce anabolic effects among patients who receive maintenance hemodialysis . A r and omized 2 x 2 factorial trial of anabolic steroid administration and resistance exercise training was conducted in 79 patients who were receiving maintenance hemodialysis at University of California , San Francisco-affiliated dialysis units . Interventions included double-blinded weekly n and rolone decanoate ( 100 mg for women ; 200 mg for men ) or placebo injections and lower extremity resistance exercise training for 12 wk during hemodialysis sessions three times per week using ankle weights . Primary outcomes included change in lean body mass ( LBM ) measured by dual-energy x-ray absorptiometry , quadriceps muscle cross-sectional area measured by magnetic resonance imaging , and knee extensor muscle strength . Secondary outcomes included changes in physical performance , self-reported physical functioning , and physical activity . Sixty-eight patients completed the study . Patients who received n and rolone decanoate increased their LBM by 3.1 + /- 2.2 kg ( P < 0.0001 ) . Exercise did not result in a significant increase in LBM . Quadriceps muscle cross-sectional area increased in patients who were assigned to exercise ( P = 0.01 ) and to n and rolone ( P < 0.0001 ) in an additive manner . Patients who exercised increased their strength in a training-specific fashion , and exercise was associated with an improvement in self-reported physical functioning ( P = 0.04 compared with nonexercising groups ) . N and rolone decanoate and resistance exercise produced anabolic effects among patients who were on hemodialysis . Further studies are needed to determine whether these interventions improve survival Skeletal muscle wasting is common and insidious in patients who receive maintenance hemodialysis treatment for the management of ESRD . The objective of this study was to determine whether 12 wk of high-intensity , progressive resistance training ( PRT ) administered during routine hemodialysis treatment could improve skeletal muscle quantity and quality versus usual care . Forty-nine patients ( 62.6 + /- 14.2 yr ; 0.3 to 16.7 yr on dialysis ) were recruited from the outpatient hemodialysis unit of the St. George Public Hospital ( Sydney , Australia ) . Patients were r and omized to PRT + usual care ( n = 24 ) or usual care control only ( n = 25 ) . The PRT group performed two sets of 10 exercises at a high intensity ( 15 to 17/20 on the Borg Scale ) using free weights , three times per week for 12 wk during routine hemodialysis treatment . Primary outcomes included thigh muscle quantity ( cross-sectional area [ CSA ] ) and quality ( intramuscular lipid content via attenuation ) evaluated by computed tomography scan . Secondary outcomes included muscle strength , exercise capacity , body circumference measures , proinflammatory cytokine C-reactive protein , and quality of life . There was no statistically significant difference in muscle CSA change between groups . However , there were statistically significant improvements in muscle attenuation , muscle strength , mid-thigh and mid-arm circumference , body weight , and C-reactive protein in the PRT group relative to the nonexercising control group . These findings suggest that patients with ESRD can improve skeletal muscle quality and derive other health-related adaptations solely by engaging in a 12-wk high-intensity PRT regimen during routine hemodialysis treatment sessions . Longer training duration s or more sensitive analysis techniques may be required to document alterations in muscle CSA OBJECTIVE As known abnormalities exist in the insulin-like growth factor ( IGF ) system in chronic kidney disease ( CKD ) patients , the measurement of bioactive IGF-I may provide further insight into the therapeutic potential of long-term exercise training . DESIGN Patients ( N=21 ) with stages 3 and 4 CKD were recruited from a local nephrology practice in Springfield , MA and r and omized into matched treatment and control groups . The treatment group participated in 48 weeks of supervised , progressive exercise training and dietary counseling , while the control group received only usual care . Treadmill testing , anthropometric measurements , and blood sample s for analysis of immunoreactive IGF-I , IGF-II , IGFBP-1 and -2 , and bioactive IGF-I were taken at baseline , 24 weeks , and 48 weeks . RESULTS There were no significant differences in any of the components of the IGF system ( all p-values>0.05 ) . Immunoreactive IGF-I levels correlated significantly with bioactive IGF-I at baseline ( r=0.50 , p=0.02 ) and at 48 weeks ( r=0.64 , p=0.01 ) . There was a significant interaction between group and time for both VO(2peak ) ( p=0.03 ) and total treadmill time ( TT ) ( p<0.01 ) . CONCLUSIONS Despite improvements in physical performance , a 48-week training program did not affect any of the circulating IGF system measurements . Disparities between these findings and those of other research ers reporting a biphasic response to long-term training may be explained by differences in study groups and exercise programs PURPOSE The current pilot and feasibility study was design ed to examine the effect of 48 wk of moderate-intensity exercise training and dietary modification on kidney function and vascular parameters in chronic kidney disease ( CKD ) patients . METHODS Twenty-one stage 2 - 4 CKD patients ( age , 18 - 70 yr ) were r and omly assigned to either the training group ( TG , n = 10 ) or the usual care group ( n = 11 ) for 48 wk . The TG received 48 wk of personal training ( 3 d·wk for up to 55 min per session at 50%-60 % V˙O2peak ) and dietary counseling , whereas individuals in the usual care group received st and ard of care and were instructed not to start a structured exercise program while in the study . V˙O2peak , estimated glomerular filtration rate ( eGFR ) , resting and ambulatory HR , plasma lipids ( total cholesterol , LDL cholesterol , HDL cholesterol , and triglycerides ) , and inflammatory markers ( high-sensitivity C-reactive protein and interleukin 6 ) were assessed at baseline and weeks 24 and 48 . An independent group 's t-test was used to compare glomerular filtration rate slopes between groups , whereas all other data were analyzed with ANCOVA using the baseline value as the covariate . RESULTS There were no statistically significant differences in any of the parameters at baseline . The 48-wk intervention led to a significant increase in V˙O2peak , reductions in both resting and ambulatory HR , and increases in LDL cholesterol and in TG , but it had no effect on the rate of change of eGFR over time . CONCLUSIONS A 48-wk exercise training program , primarily focused on aerobic exercise , increases V˙O2peak and favorably alters autonomic function as evidence d by reductions in HR in stages 2 - 4 CKD patients . The exercise intervention had no effect on kidney function as assessed by eGFR BACKGROUND AND OBJECTIVES Patients with CKD have a high prevalence of cardiovascular disease associated with or exacerbated by inactivity . This r and omized , controlled study investigated whether a renal rehabilitation exercise program for patients with stages 3 or 4 CKD would improve their physical function and quality of life . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS In total , 119 adults with CKD stages 3 and 4 were r and omized , and 107 of these patients proceeded to usual care or the renal rehabilitation exercise intervention consisting of usual care plus guided exercise two times per week for 12 weeks ( 24 sessions ) . Physical function was determined by three well established performance-based tests : 6-minute walk test , sit-to-st and test , and gait-speed test . Health-related quality of life was assessed by the R AND 36-Item Short Form Health Survey . RESULTS At baseline , no differences in self-reported level of activity , 6-minute walk test , and sit-to-st and test scores were observed between the usual care ( n=48 ) and renal rehabilitation exercise ( n=59 ) groups , although baseline gait-speed test score was higher in the renal rehabilitation exercise group ( P<0.001 ) . At follow-up , the renal rehabilitation exercise group but not the usual care group showed significant improvements in the 6-minute walk test ( + 210.4±266.0 ft [ 19 % improvement ] versus -10±219.9 ft ; P<0.001 ) , the sit-to-st and test ( + 26.9±27 % of age prediction [ 29 % improvement ] versus + 0.7±12.1 % of age prediction ; P<0.001 ) , and the R AND -36 physical measures of role functioning ( P<0.01 ) , physical functioning ( P<0.01 ) , energy/fatigue levels ( P=0.01 ) , and general health ( P=0.03 ) and mental measure of pain scale ( P=0.04 ) . The renal rehabilitation exercise regimen was generally well tolerated . CONCLUSIONS A 12-week/24-session renal rehabilitation exercise program improved physical capacity and quality of life in patients with CKD stages 3 and 4 . Longer follow-up is needed to determine if these findings will translate into decreased mortality rates Patients on hemodialysis ( HD ) show changes in muscle structure and function reducing their functional capacity . This study was conduted to assess the effects of respiratory muscle training ( RMT ) and peripheral muscle training ( PMT ) during dialysis on functional parameters , inflammatory state , and quality of life ( QoL ) in patients on HD . R and omized controlled trial included 39 patients on HD , and they were divided into three groups : RMT ( n = 11 ) , PMT ( n = 14 ) , and controls ( C , n = 14 ) . Training was performed during the HD session for 10 weeks . Maximal inspiratory pressure ( PImax ) , maximal expiratory pressure ( PEmax ) , forced vital capacity ( FVC ) , six-minute walk test ( 6MWT ) , Kt/Vsp , biochemical parameters , and inflammatory state ( i.e. , level of high sensitivity C-reactive protein ) were evaluated . Variation from baseline was calculated by Analysis of Covariance ( ANCOVA ) . The ΔPImax was 22.5 ± 3.2 , 9.1 ± 2.9 , and −4.9 ± 2.8 cmH2O in the RMT , PMT and C , respectively ( p < 0.001 ) ; ΔPEmax was 10.8 ± 6.6 , 3.7 ± 5.9 , and −15.6 ± 5.9 cmH2O respectively ( p = 0.014 ) . The Δ6MWT was significantly greater in RMT and PMT ( 65.5 ± 9 ; 30.8 ± 8 m ) than in C ( −0.5 ± 8.1 m ) , p < 0.001 . Although biochemical parameters decreased after training , Kt/V remained unchanged . CRP decreased only in the RMT and PMT groups . There was a significant increase in QoL scores in the training groups ( vs. C ) in energy/fatigue ( p = 0.002 ) , sleep ( p < 0.001 ) , pain ( p < 0.001 ) , and list of symptoms/problems ( p = 0.014 ) . A short period of RMT or PMT during HD significantly improved functional capacity , with RMT showing greater effect than PMT . Muscle training improved biochemical and inflammatory markers , but a direct cause and effect relationship could not be established by this study |
12,987 | 22,217,214 | Adverse events were similar across treatment groups but were poorly reported . | Background Artemisinin-based combinations are recommended for treatment of uncomplicated falciparum malaria , but are costly and in limited supply .
Clindamycin plus quinine is an alternative non-artemisinin-based combination recommended by World Health Organization .
The efficacy and safety of clindamycin plus quinine is not known .
This systematic review aims to assess the efficacy of clindamycin plus quinine versus other anti-malarial drugs in the treatment of uncomplicated falciparum malaria . | BACKGROUND Between 1995 and 2000 , KwaZulu-Natal province , South Africa , experienced a marked increase in Plasmodium falciparum malaria , fuelled by pyrethroid and sulfadoxine-pyrimethamine resistance . In response , vector control was strengthened and artemether-lumefantrine ( AL ) was deployed in the first Ministry of Health artemisinin-based combination treatment policy in Africa . In South Africa , effective vector and parasite control had historically ensured low-intensity malaria transmission . Malaria is diagnosed definitively and treatment is provided free of charge in reasonably accessible public-sector health-care facilities . METHODS AND FINDINGS We review ed four years of malaria morbidity and mortality data at four sentinel health-care facilities within KwaZulu-Natal 's malaria-endemic area . In the year following improved vector control and implementation of AL treatment , malaria-related admissions and deaths both declined by 89 % , and outpatient visits decreased by 85 % at the sentinel facilities . By 2003 , malaria-related outpatient cases and admissions had fallen by 99 % , and malaria-related deaths had decreased by 97 % . There was a concomitant marked and sustained decline in notified malaria throughout the province . No serious adverse events were associated causally with AL treatment in an active sentinel pharmacovigilance survey . In a prospect i ve study with 42 d follow up , AL cured 97/98 ( 99 % ) and prevented gametocyte developing in all patients . Consistent with the findings of focus group discussion s , a household survey found self-reported adherence to the six-dose AL regimen was 96 % . CONCLUSION Together with concurrent strengthening of vector control measures , the antimalarial treatment policy change to AL in KwaZulu-Natal contributed to a marked and sustained decrease in malaria cases , admissions , and deaths , by greatly improving clinical and parasitological cure rates and reducing gametocyte carriage Pregnant women participating in a longitudinal immuno-epidemiologic survey in Lambaréné , Gabon , and presenting with Plasmodium falciparum parasitemia at monthly blood smear examinations were offered treatment with oral 7-day quinine monotherapy according to national health guidelines . A total of 50 pregnant women were offered 7-day oral quinine sulfate 10 mg/kg thrice daily . Clinical examinations and laboratory tests were performed on Days 28 and 56 to assess the effectiveness of this st and ard regimen . By Day 28 , the effectiveness of the 7-day quinine regimen was 60 % ( 95 % confidence interval : 46 - 72 % ) . We conclude that a 7-day course of quinine has a poor effectiveness and that alternative treatment regimens for malaria in pregnant women should be assessed BACKGROUND Artemisinin-based combination therapies are the recommended first-line treatments of falciparum malaria in all countries with endemic disease . There are recent concerns that the efficacy of such therapies has declined on the Thai-Cambodian border , historically a site of emerging antimalarial-drug resistance . METHODS In two open-label , r and omized trials , we compared the efficacies of two treatments for uncomplicated falciparum malaria in Pailin , western Cambodia , and Wang Pha , northwestern Thail and : oral artesunate given at a dose of 2 mg per kilogram of body weight per day , for 7 days , and artesunate given at a dose of 4 mg per kilogram per day , for 3 days , followed by mefloquine at two doses totaling 25 mg per kilogram . We assessed in vitro and in vivo Plasmodium falciparum susceptibility , artesunate pharmacokinetics , and molecular markers of resistance . RESULTS We studied 40 patients in each of the two locations . The overall median parasite clearance times were 84 hours ( interquartile range , 60 to 96 ) in Pailin and 48 hours ( interquartile range , 36 to 66 ) in Wang Pha ( P<0.001 ) . Recrudescence confirmed by means of polymerase-chain-reaction assay occurred in 6 of 20 patients ( 30 % ) receiving artesunate monotherapy and 1 of 20 ( 5 % ) receiving artesunate-mefloquine therapy in Pailin , as compared with 2 of 20 ( 10 % ) and 1 of 20 ( 5 % ) , respectively , in Wang Pha ( P=0.31 ) . These markedly different parasitologic responses were not explained by differences in age , artesunate or dihydroartemisinin pharmacokinetics , results of isotopic in vitro sensitivity tests , or putative molecular correlates of P. falciparum drug resistance ( mutations or amplifications of the gene encoding a multidrug resistance protein [ PfMDR1 ] or mutations in the gene encoding sarco-endoplasmic reticulum calcium ATPase6 [ PfSERCA ] ) . Adverse events were mild and did not differ significantly between the two treatment groups . CONCLUSIONS P. falciparum has reduced in vivo susceptibility to artesunate in western Cambodia as compared with northwestern Thail and . Resistance is characterized by slow parasite clearance in vivo without corresponding reductions on conventional in vitro susceptibility testing . Containment measures are urgently needed . ( Clinical Trials.gov number , NCT00493363 , and Current Controlled Trials number , IS RCT N64835265 . Objective To compare the effectiveness of oral quinine with that of artemether-lumefantrine in treating uncomplicated malaria in children . Design R and omised , open label effectiveness study . Setting Outpatient clinic of Ug and a ’s national referral hospital in Kampala . Participants 175 children aged 6 to 59 months with uncomplicated malaria . Interventions Participants were r and omised to receive oral quinine or artemether-lumefantrine administered by care givers at home . Main outcome measures Primary outcomes were parasitological cure rates after 28 days of follow-up unadjusted and adjusted by genotyping to distinguish recrudescence from new infections . Secondary outcomes were adherence to study drug , presence of gametocytes , recovery of haemoglobin concentration from baseline at day 28 , and safety profiles . Results Using survival analysis the cure rate unadjusted by genotyping was 96 % for the artemether-lumefantrine group compared with 64 % for the quinine group ( hazard ratio 10.7 , 95 % confidence interval 3.3 to 35.5 , P=0.001 ) . In the quinine group 69 % ( 18/26 ) of parasitological failures were due to recrudescence compared with none in the artemether-lumefantrine group . The mean adherence to artemether-lumefantrine was 94.5 % compared with 85.4 % to quinine ( P=0.0008 ) . Having adherence levels of 80 % or more was associated with a decreased risk of treatment failure ( 0.44 , 0.19 to 1.02 , P=0.06 ) . Adverse events did not differ between the two groups . Conclusions The effectiveness of a seven day course of quinine for the treatment of uncomplicated malaria in Ug and an children was significantly lower than that of artemether-lumefantrine . These findings question the advisability of the recommendation for quinine therapy for uncomplicated malaria in Africa . Trial registration Clinical Trials.gov NCT00540202 BACKGROUND Artemisinin-based drug combinations are the mainstay in the fight against drug-resistant malaria in Africa . Currently available antimalarial drug combinations that include artemisinins are pharmacokinetically unmatched and are therefore potentially increasing the risk of selection of resistant mutants in areas in which the rate of transmission of malaria is high . We tested the potential value of artemisinin-based combination therapy with a short elimination half-life for the treatment of uncomplicated Plasmodium falciparum malaria in sub-Saharan Africa . METHODS We conducted an open-label , r and omized , controlled clinical trial to evaluate the efficacy and tolerability of oral artesunate-clindamycin therapy given twice daily for 3 days ( artesunate , 2 mg/kg , and clindamycin , 7 mg/kg , per dose ) , compared with a st and ard quinine-clindamycin regimen given twice daily for 3 days ( quinine , 15 mg/kg , and clindamycin , 7 mg/kg , per dose ) , for the treatment of uncomplicated falciparum malaria in 100 Gabonese children aged 3 - 12 years . The primary end point of the study was the polymerase chain reaction-corrected cure rate for the per- protocol population . RESULTS The activity of artesunate-clindamycin was comparable to that of quinine-clindamycin in the per- protocol analysis of cure rates at day 28 of follow-up ( 87 % versus 94 % ) . No serious adverse events were reported , and tolerability was good and was similar in both groups . Times to clearance of fever and clearance of parasites were significantly shorter in the artesunate-clindamycin group . CONCLUSIONS Artesunate-clindamycin and other matching artemisinin-based combinations with a short plasma half-life merit further attention for use in regions in which the rate of transmission of malaria is high ABSTRACT Therapeutic responses to clindamycin in combination with quinine were assessed in adult Thai patients with uncomplicated multidrug-resistant Plasmodium falciparum malaria . In total 204 patients were r and omized to receive a 7-day oral treatment regimen of quinine ( Q7 ) either alone ( n = 68 ) , in combination with clindamycin ( Q7C7;n = 68 ) , or in combination with tetracycline ( Q7T7 ; n = 68 ) . All patients had uncomplicated recoveries with no serious adverse effects . Fever clearance times for both of the two combination regimens ( median of 47 h and range of 8 to 120 h for Q7C7 and median of 36 h and range of 8 to 117 h for Q7T7 ) were significantly shorter than that for the Q7-only regimen ( median , 56 ; range , 4 to 152 h ) ( P = 0.002 ) . Parasite clearance times ( overall mean ± st and ard deviation , 78 ± 23 h ) were not significantly different between the three treatment groups ( P = 0.98 ) . The cure rates assessed at 28 days of follow-up were 100 % for Q7C7 and 98 % for Q7T7 , whereas the cure rate was 87 % for the Q7-only regimen ( P ≤ 0.04 ) . Clindamycin in combination with quinine is a safe and effective treatment for multidrug-resistant P. falciparum malaria . This combination may be of particular value in children and pregnant women , in whom tetracyclines are contraindicated ABSTRACT We conducted a r and omized , double-blind , placebo-controlled trial to compare a 3-day quinine-clindamycin regimen ( group QC ) with a 7-day quinine regimen ( group Q ) for the treatment of uncomplicatedPlasmodium falciparum malaria in travelers returning from the tropics . A total of 55 and 53 patients in groups Q and QC were analyzed , respectively . Adverse effects were similar in both groups , although two patients in group Q had severe adverse reactions , leading to the cessation of treatment . The 28-day cure rate for the evaluated patients ( per- protocol analysis ) was 100 % for group QC , whereas it was 96.3 % for group Q ( P = 0.5 ) . The 28-day cure rate in the intention-to-treat analysis was 96.2 % for group QC , whereas it was 94.6 % for group Q ( P = 1 ) . There were no significant differences between the two regimens with regard to parasite and fever clearance times . Our study shows that the 3-day quinine-clindamycin regimen is well tolerated and compares favorably with a 7-day quinine treatment . This short-term regimen had previously been evaluated only in areas of endemicity . According to our results , the 3-day quinine-clindamycin regimen may be an alternative for the treatment of imported uncomplicated P. falciparum malaria in travelers returning from the tropics In this open r and omized trial comparing 3-day oral quinine-clindamycin versus st and ard mefloquine regimen for uncomplicated imported falciparum malaria , mefloquine treatment was associated with a higher risk of discontinuation of the treatment ( RR=1.8 , 95 % CI [ 1.1 - 2.8 ] ) related to mainly mild gastrointestinal adverse drug events . The poor tolerability of mefloquine sets a question mark against its use in out patients The frequency of antibiotic-associated diarrhoea ( AAD ) and Clostridium difficile-associated diarrhoea ( CdAD ) was prospect ively determined in a population of 2462 patients recruited from five Swedish hospitals , including divisions for infectious diseases , orthopaedics , surgery , geriatrics , nephrology and internal medicine . AAD developed in 4.9 % of the treated patients . Faecal sample s were obtained from 69 % of patients with AAD and 55.4 % were positive for C. difficile cytotoxin B. The frequency of AAD varied from 1.8 to 6.9 % at the participating centres ( P < 0.001 ) . The frequency of AAD also varied considerably between medical disciplines and wards within different hospitals and was highest in the nephrology and geriatric units ( 6.7 and 7.1 % , respectively ) . There was no difference in frequency of AAD when analysed with respect to gender or age . Medical interventions ( laxative treatment , endoscopy and abdominal surgery ) or presence of one concomitant disease ( diabetes , malignancy , chronic renal disease and inflammatory bowel disease ) did not significantly affect the frequency of AAD , whereas patients suffering from two or more of these illnesses had significantly ( P = 0.001 ) higher frequencies of AAD . Patients treated with antibiotics for 3 days had a significantly ( P = 0.009 ) lower frequency of AAD than those treated for longer periods . Treatment with cephalosporins , clindamycin or broad-spectrum penicillins was associated with an increased risk of AAD . With specimens from one centre , 62.5 % of tested patients with AAD and 33.8 % of asymptomatic patients were positive for cytotoxin B. Although C. difficile cytotoxin B in stool sample s was significantly associated with AAD ( P = 0.003 ) , the causal relationship with diarrhoea is not always evident OBJECTIVE To assess the efficacy and tolerability of quinine-doxycycline combination therapy in uncomplicated falciparum malaria in terms of malarial parasite clearance from peripheral blood . METHODS One hundred adult males were included in the study . Malarial parasite counts in peripheral blood films were determined at the time of admission and then 12 hourly until clearance and thereafter weekly for 28 days ( 4 weeks ) . Treatment was started with quinine sulphate 10 mg of salt/kg body weight 8 hourly orally for a minimum period of 3 days and maximum of 7 days along with doxycycline 100 mg 12 hourly orally for 7 days . Primary efficacy outcome measure was early treatment failure , whereas secondary efficacy outcome measure was late treatment failure . Tolerability outcome measure was the development of treatment related adverse effects result ing in discontinuation from the study . RESULTS The primary efficacy outcome measure of the study i.e. malarial parasite index declined from a mean of 6.34 ( SD + /- 2.83 ) before treatment to zero at day 7 of treatment . Parasite clearance time was 1 - 7 days ( mean 3.58 , SD + /- 1.28 ) . Mean duration of quinine treatment till clearance of malarial parasites was 4.63 days ( SD + /- 1.38 ) . Mean duration of fever was 2.96 days ( range 1 to 6 days ) . There was no early or late treatment failure . There was no relapse during the 28 days follow up period . Drug related side effects were mild and did not warrant discontinuation of treatment in any patient . CONCLUSION Quinine-doxycycline combination is effective in southern Pakistan . R and omized controlled trials are needed to further vali date the cl aim Childhood anaemia is a major public health problem in malaria holoendemic areas . We assessed the effects of antimalarial treatment in an area with drug-resistant falciparum malaria on haemoglobin levels in small children by applying the 1996 World Health Organization in vivo method for the evaluation of st and ard chloroquine treatment at the community level . In Fukayosi village , coastal Tanzania , 117 children aged 5 - 36 months with clinical malaria episodes were treated with chloroquine syrup ( 25 mg/kg ) . Early treatment failure ( ETF ) occurred in 20 % and late treatment failure ( LTF ) in 22 % of cases . Age > 1 year and malnutrition were protective factors against ETF . The evidence that chloroquine treatment could not prevent an exacerbation of anaemia was ( i ) the fact that the fall in haemoglobin level after 72 h was significantly greater in ETF than in children with LTF and an adequate clinical response , and ( ii ) the absence of any haematological improvement at follow-up in children receiving chloroquine alone , even in true treatment successes . In contrast , pyrimethamine/sulfadoxine administered to treatment failures improved the haemoglobin level significantly > 21 d after treatment started ( mean difference 14 g/L , 95 % confidence interval 2.1 - 27 ) . We conclude that , when chloroquine treatment of childhood malaria is associated with a 20 % ETF rate , the haemoglobin response is unsatisfactory and there is a need to change the recommended first-line treatment Plasmodium falciparum in Southeast Asia is highly resistant to chloroquine and sulfadoxine/ pyrimethamine . Quinine-tetracycline has been used as a second line treatment for uncomplicated falciparum malaria , but duration of treatment varies from place to place . The 7-days course of this combination has been shown to be very effective . However , due to the cinchonism adverse effects , the patient compliance has not been satisfactory . We have evaluated the efficacy of a 7-days course of tetracycline in combination with either 5 or 7-days course of quinine . Ninety male Thai patients who were admitted to the Bangkok Hospital for Tropical Diseases were r and omized to receive tetracycline 250 mg qid for 7 days in combination with either quinine 600 mg tid for 5 days ( Q5T7 ; group A ) or quinine 600 mg tid for 7 days ( Q7T7 ; group B ) . The patients were hospitalized for 28 days . Patients in both groups had a comparable initial response to treatment , with the clearance of fever and parasites within 4 days . There were 46 and 40 patients in group A and B , respectively , who completed the 28 day of follow-up . The cure rates were 87 and 100 % , respectively for group A and B. No serious adverse effects were found in either group ; transient nausea , vomiting and tinnitus were common findings . The incidence of adverse effects was not different between the two groups . The results from the present study suggest that a short course treatment of quinine ( Q5T7 ) had significantly decreased the cure rate . In areas with quinine resistant falciparum malaria , a full course of 7-days quinine , in combination with 7-days course of tetracycline is recommended for hospital treatment . However , an alternative shorter course of antimalarials is suggested for home treatment In areas where multidrug-resistant Plasmodium falciparum ( MDR-Pf ) is prevalent , only quinine is known to be safe and effective in pregnant women . On the western border of Thail and , 7 days of supervised quinine ( 30 mg/kg daily ) cures two-thirds of P. falciparum-infected women in the 2nd and 3rd trimesters of pregnancy . Artesunate is effective against MDR-Pf and the limited data on its use in pregnancy suggest it is safe . An open r and omized comparison of supervised quinine ( 10 mg salt/kg every 8 h ) in combination with clindamycin ( 5 mg/kg every 8 h ) for 7 days ( QC7 ) versus artesunate 2 mg/kg per day for 7 days ( A7 ) was conducted in 1997 - 2000 in 129 Karen women with acute uncomplicated falciparum malaria in the 2nd or 3rd trimesters of pregnancy . There was no difference in the day-42 cure rates between the QC7 ( n = 65 ) and A7 ( n = 64 ) regimens with an efficacy of 100 % in both , confirmed by parasite genotyping . The A7 regimen was also associated with less gametocyte carriage ; the average person-gametocyte-weeks for A7 was 3 ( 95 % CI 0 - 19 ) and for QC7 was 39 ( 95 % CI 21 - 66 ) per 1000 person-weeks , respectively ( P < 0.01 ) . There was no difference in gastrointestinal symptoms between the groups but there was significantly more tinnitus in the QC7 group compared to the A7 group ( 44.9 % vs 8.9 % ; RR 5.1 ; 95 % CI 1.9 - 13.5 ; P < 0.001 ) . The favourable results with quinine-clindamycin mean that there is a useful back-up treatment for women with falciparum malaria who experience quinine and artesunate failures in pregnancy . Adherence to the 7-day regimen and cost ( US$ 18.50 per treatment ) are likely to be the main obstacles to this regimen Abstract The efficacy of clindamycin , a slow acting antimalarial , in combination with a rapid acting schizonticidal drug , quinine , was determined against three multidrug-resistant strains of Plasmodium falciparum ( Cambodian I , Burma [ Thau ] and Panama II ) . No recrudescences occurred after treatment with quinine 650 mg orally every 8 hours for 3 days and clindamycin 450 mg orally every 6 hours for 3 days , when administered either simultaneously or sequentially . Quinine alone for 3 days was not curative against infections with these strains . During a 3-day course of therapy , blood levels of quinine or clindamycin were not influenced by administration of the other drug Over 12 years , from 1984 to 1995 , we conducted a prospect i ve study of overall and malaria specific mortality among three rural population s in the Sahel , savanna and forest areas of Senegal . The emergence of chloroquine resistance has been associated with a dramatic increase in malaria mortality in each of the studied population s. After the emergence of chloroquine resistance , the risk of malaria death among children 0 - 9 years old in the three population s was multiplied by 2.1 , 2.5 and 5.5 , respectively . This is the first study to document malaria mortality at the community level in Africa before and after the emergence of chloroquine resistance . Findings suggest that the spread of chloroquine resistance has had a dramatic impact on the level of malaria mortality in most epidemiological context s in tropical Africa In a r and omized trial , a three-dose quinine monotherapy was compared with short-term combination regimens of quinine-clindamycin and quinine-doxycycline for treating adult Gabonese patients with Plasmodium falciparum malaria . In quinine-treated patients , only 38 % were ultimately cured . In contrast , more than 90 % of patients were cured after treatment with either combination regimen The efficacy of a 3-day clindamycin-quinine regimen to treat clinical malaria attacks was investigated in 256 children from western Gabon . Treatment was well tolerated by all of the children and its efficacy was higher than 97 % by day 20 . Thus this 3-day clindamycin-quinine regimen might constitute a potential alternative to chloroquine for treating clinical malarial attacks in children from Gabon |
12,988 | 21,760,503 | Several controlled r and omized studies and systematic review s indicate that immune nutrition formulas reduce both morbidity and length of stay after major abdominal surgery .
Current data shows that the use of perioperative immunonutrition diets for major abdominal surgery is beneficial . | PURPOSE OF REVIEW This article review s the recent research on perioperative nutrition in digestive tract surgery in the light of modern perioperative care principles , that is , enhanced recovery after surgery ( ERAS ) .
The use of ERAS elements to reduce surgical stress and preclude postoperative insulin resistance has recently been clearly linked to reductions in adverse outcomes . | BACKGROUND & AIM The immunomodulating nutrition was supposed to reduce the incidence of complications in surgical patients , but many authors have question ed its value recently . The aim of the study was to assess the impact of enteral immunonutrition in postoperative period . METHODS Between January 2003 and December 2009 , 305 malnourished patients ( 123 F , 182 M , m. age 60.8 ) undergoing resection for pancreatic or gastric cancer , after preoperative 14 days of parenteral feeding , were r and omized in double-blind manner to receive either postoperative immunomodulating enteral diet ( IMEN ) or st and ard oligopeptide diet ( SEN ) . Outcome measures of the intend-to-treat analysis were : number and type of complications , length of hospitalization , mortality , and vital organ function . RESULTS Median postoperative hospital stay was 17.1 days in SEN and 13.1 days in IMEN group ( p = 0.006 ) . Infectious complications were observed in 60 patients ( 39.2 % ) in SEN and 43 ( 28.3 % ) in IMEN group ( p = 0.04 ) . Differences were also observed in overall morbidity ( 47.1 vs 33.5 % , p = 0.01 ) and mortality ( 5.9 vs 1.3 % , p = 0.03 ) , but the ratio of surgical complications , organ function , and treatment tolerance did not differ . CONCLUSIONS The study proved that postoperative immunomodulating enteral nutrition should be the treatment of choice in malnourished surgical cancer patients . The Clinical Trials Data base registry number : NCT00576940 OBJECTIVES To study the impact of different adherence levels to the enhanced recovery after surgery ( ERAS ) protocol and the effect of various ERAS elements on outcomes following major surgery . DESIGN Single-center prospect i ve cohort study before and after reinforcement of an ERAS protocol . Comparisons were made both between and across periods using multivariate logistic regression . All clinical data ( 114 variables ) were prospect ively recorded . SETTING Ersta Hospital , Stockholm , Sweden . PATIENTS Nine hundred fifty-three consecutive patients with colorectal cancer : 464 patients treated in 2002 to 2004 and 489 in 2005 to 2007 . MAIN OUTCOME MEASURES The association between improved adherence to the ERAS protocol and the incidence of postoperative symptoms , complications , and length of stay following major colorectal cancer surgery was analyzed . RESULTS Following an overall increase in preoperative and perioperative adherence to the ERAS protocol from 43.3 % in 2002 to 2004 to 70.6 % in 2005 to 2007 , both postoperative complications ( odds ratio , 0.73 ; 95 % confidence interval , 0.55 - 0.98 ) and symptoms ( odds ratio , 0.53 ; 95 % confidence interval , 0.40 - 0.70 ) declined significantly . Restriction of intravenous fluid and use of a preoperative carbohydrate drink were major independent predictors . Across periods , the proportion of adverse postoperative outcomes ( 30-day morbidity , symptoms , and readmissions ) was significantly reduced with increasing adherence to the ERAS protocol ( > 70 % , > 80 % , and > 90 % ) compared with low ERAS adherence ( < 50 % ) . CONCLUSION Improved adherence to the st and ardized multimodal ERAS protocol is significantly associated with improved clinical outcomes following major colorectal cancer surgery , indicating a dose-response relationship OBJECTIVE To evaluate the influence of postoperative immunonutrition on immune and nutritional parameters in patients with gastric carcinoma . METHODS From September 2002 to August 2003 , 40 patients with gastric carcinoma who had undergone major surgery were r and omly divided into an immunonutrition group and st and ard nutrition group , each of 20 patients . On postoperative Day 2 , patients in the st and ard nutrition group received a st and ard enteral formula , while those in the immunonutrition group received an enteral formula enriched with glutamine , arginine and omega-3 fatty acids . Nutritional support was continued for 7 days . Blood sample s were obtained to determine plasma albumin , prealbumin and transferrin on Days 0 , 5 and 9 . On Days 0 , 1 and 9 , blood sample s were collected to detect immunoglobulin ( Ig ) A , IgG , IgM , CD4 and CD8 cell counts , the ratio of CD4/CD8 , interleukin (IL)-2 , IL-6 and tumour necrosis factor (TNF)-alpha , respectively . RESULTS There were no significant differences between the two groups in protein and immune parameters preoperatively and no significant differences in management perioperatively . No serious adverse effects were recorded with the two formulas . Postoperative procedures were smooth in both groups . On Day 9 , serum levels of prealbumin and transferrin were higher in the immunonutrition group than in the st and ard nutrition group ( p<0.01 ) . After 7 days ' nutritional support , patients in the immunonutrition group had higher levels of immunoglobulin , CD4 cell counts , CD4/CD8 ratio and IL-2 than those in the control group , whereas IL-6 and TNF-alpha levels were significantly lower in the immunonutrition group . CONCLUSION Compared with st and ard enteral nutrition , enteral immunonutrition can improve defence mechanisms and modulate inflammatory action after major elective surgery for gastric carcinoma Objective The authors determined the effect of glutamine-supplementation of TPN on postoperative peripheral blood T-cell response and proinflammatory cytokine production in patients undergoing colorectal resection . Summary Background Data Several vital tissues , including the immune system , are very dependent on glutamine ; however , this amino acid , which may be essential in conditions of stress , only now is becoming formulated suitably for incorporation into TPN . The effects of such supplementation on the immune function of stressed surgical patients is unknown . Methods Patients ( n = 20 ) were r and omized to receive conventional TPN ( 0.2 g nitrogen/kg/d ) or an isonitrogenous/isocaloric regimen with 0.18 g of glutamine/kg/d from days 1 to 6 postoperatively . T-cell DNA synthesis and interleukin (IL)-2 production and peripheral blood mononuclear cell IL-6 and tumor necrosis factor ( TNF ) production were measured in vitro preoperatively and on days 1 and 6 postoperatively . Results T-cell DNA synthesis after 5 days of TPN was increased compared with preoperative values in the glutamine-supplemented group ( median preoperative tritiated thymidine uptake : 78.3 X 103 cpm , day 6 : 95.0 X 103 cpm , p < 0.05 ) . There was no such increase in the control TPN group ( preoperative : 89.0 X 103 cpm , day 6 : 69.4 X 103 cpm , p > 0.05 ) . Glutamine supplementation did not influence IL-2 production or the production of TNF or IL-6 . Conclusions Glutamine supplementation may be a method of enhancing T-cell function in the surgical patient receiving TPN Specific immunonutrients may reduce the incidence of postoperative complications and shorten recovery time . This r and omized trial evaluated the clinical efficacy of a fish oil emulsion on outcome and immune function after gastrointestinal cancer surgery BACKGROUND & AIMS Malnutrition is a recognized risk factor for perioperative morbidity , but there is currently no st and ardized definition of malnutrition . The Nutrition Risk Screening 2002 score was recently proposed to identify patients at nutritional risk who may benefit from nutritional support therapy , and has been officially adopted by the European Society of Parenteral and Enteral Nutrition . The aim of this study was to assess the value of the Nutrition Risk Screening 2002 score in predicting the incidence and severity of postoperative complications in gastrointestinal surgery . METHODS We prospect ively evaluated 608 patients admitted for elective gastrointestinal surgery . Nutritional risk was defined by the Nutrition Risk Screening 2002 score and correlated to the incidence and severity of postoperative complications . Complications were classified using an established surgical complication classification . RESULTS The overall incidence of nutritional risk was 14 % . We observed a significantly higher complication rate of 40 % ( 35 out of 87 ) in patients at nutritional risk , compared to 15 % ( 81 out of 521 ) in patients with a normal score ( p<0.001 ) . The incidence of severe complications was significantly higher in patients at nutritional risk ( 54 % versus 15 % ; p<0.001 ) . The odds ratio to develop a complication was 2.8 in patients at risk ( p=0.001 ) , and 3.0 in patients with malignant disease ( p<0.001 ) . The median length of stay in nutritional risk patients was significantly longer ( 10 versus 4 days , p<0.001 ) . CONCLUSION The prevalence of nutritional risk patients in gastrointestinal surgery is high . We showed that nutritional risk screening using the NRS 2002 strongly predicts the incidence and severity of complications BACKGROUND Malnutrition in gastrointestinal ( GI ) surgery is associated with increased morbidity . Therefore , careful screening remains crucial to identify patients at risk for malnutrition and consequently postoperative complications . The aim of this study was to evaluate the ability of 3 established score systems to identify patients at risk of developing postoperative complications in GI surgery and to assess the correlation among the score systems . METHODS We evaluated prospect ively 200 patients admitted for elective GI surgery using ( 1 ) nutrition risk index , ( 2 ) nutrition risk score , and ( 3 ) bioelectrical impedance analysis . Complications were assessed using a st and ardized complication classification . The findings of the score systems were correlated with the incidence and severity of complications . Parametric and nonparametric correlation analysis was performed among the different score systems . RESULTS All 3 score systems correlated significantly with the incidence and severity of postoperative complications and the duration of hospital stay . Using multiple regression analysis , only nutrition risk score and malignancy remained prognostic factors for the development of complications with odds ratios of 4.2 ( P = .024 ) and 5.6 ( P < .001 ) , respectively . The correlation between nutrition risk score and nutrition risk index was only moderate ( Pearson coefficient = 0.54 ) . Bioelectrical impedance analysis displayed only weak to trivial correlation to the nutrition risk index ( 0.32 ) and nutrition risk score ( 0.19 ) , respectively . CONCLUSION The nutrition risk score , nutrition risk index , and bioimpedance analysis correlate with the incidence and severity of perioperative complications in GI surgery . The nutrition risk score was the best score in predicting patients who will develop complications in this study population . The correlation between the individual scores was only moderate , and therefore , they do not necessarily identify the same patients BACKGROUND The aim of this trial was to compare multimodal optimization with conventional perioperative management in a consecutive series of patients undergoing gastrectomy procedures . METHODS According to r and omized controlled studies and conclusions made by meta-analyses in colorectal surgery , optimized perioperative measures were design ed and applied in gastrectomy surgery . Thirty-three patients were r and omized to the optimized group and 30 patients to a control group . Two groups were treated in 1 center by a single surgical team in different wards . Both groups used patient-controlled intravenous analgesia for postoperative analgesia . The primary end point was length of postoperative hospital stay . Secondary outcomes included bowel function recovery after surgery , perioperative changes of inflammatory factors , glucocorticoid , insulin resistance , and body composition . Perioperative complications and adverse events were also recorded . RESULTS The groups were similar in terms of age , sex ratio , and Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity ( POSSUM score ) . The optimized group was associated with a significantly shorter postoperative hospital stay compared with the conventional care group ( P < .001 ) . Duration s of urinary catheterization and abdominal drainage were also less ( P < .001 ) . The diet program in the optimization group was well tolerated and was associated with an earlier recovery of gut function ( P < .001 ) . Proinflammatory factors were less elevated and body composition was more stable in the optimized group than in controls . There were no differences in morbidity or mortality between the groups . CONCLUSIONS Optimization of care in gastrectomy can shorten postoperative hospital stay and provides multiple beneficial outcomes , including hastening the return of gut function , without increasing morbidity Surgical injury provokes a stress response that leads to a catabolic state and , when prolonged , interferes with the postoperative recovery process . This study tests the impact of 2 nutrition support regimens on protein and glucose metabolism as part of an integrated approach in the perioperative period incorporating epidural analgesia in 18 nondiabetic patients undergoing colorectal surgery . To test the hypothesis that parenteral amino acid infusion ( amino acid group , n = 9 ) maintains glucose homeostasis while maintaining normoglycemia and reduces proteolysis compared with infusion of dextrose alone ( DEX group , n = 9 ) , glucose and protein kinetics were measured before and on the second day after surgery using a stable isotope tracer technique . Postoperatively , the rate of appearance of glucose was higher ( P < .001 ) and blood glucose increased more ( P < .001 ) in the DEX group than in the amino acid group . The postoperative increase in the appearance of leucine from protein breakdown tended to be greater ( P = .077 ) in the DEX group . We conclude that perioperative infusion of a nutrition support regimen delivering amino acids alone maintains blood glucose homeostasis and normoglycemia and tends to have a suppressive effect on protein breakdown compared with infusion of dextrose alone Introduction : Current studies suggest immunonutrition decreases the inflammatory process , infection rates and reduces length of hospital stay in surgical patients , however studies are often conducted on heterogeneous groups of patients with varying composition of the immunonutrition . We aim to investigate the effect of immunonutrition on patients undergoing major upper gastrointestinal surgery by assessment of ( i ) the inflammatory and immune response and ( ii ) changes in clinical outcome when compared to a r and omised control receiving conventional feeding . Method : A prospect i ve double-blind r and omised controlled study was undertaken to compare a feed supplemented with glutamine , arginine , ω-3 fatty acids and tributyrin , vitamin C , E and B-carotene and micronutrients ( zinc , selenium and chromium ) to an isonitrogenous , isocaloric control feed in patients undergoing major upper GI surgery . The primary end-points were defined as C-reactive protein ( CRP ) , prealbumin and retinol binding protein ( RBP ) levels . Secondary end-points included performance scoring systems , length of hospital stay , adverse events and protein and nutrient assays . Variables were measured pre-operatively and routinely up to the 4th post-operative day . Results : There was no statistically significant change in primary end-points between the immunonutrition group and the control group . There was no difference in length of hospital stay between the groups . The vitamin C level in the study group was significantly higher at the end of the study period . Both groups tolerated the feeds well with adequate target feeding rate . There were no other significant changes in clinical outcomes between the two groups . Conclusion : This study has not shown a benefit of immunonutrition through changes in inflammatory or nutritional markers , a decrease in length of hospital stay , or other morbidity . This may be because of inadequate numbers recruited to the study . Further , multi-centre , r and omised trials on homogeneous patient groups are necessary to investigate the role of immunonutrition in major upper GI surgery Background Studies showing the improvement of insulin sensitivity by reducing the term of preoperative fasting are mostly done in patients undergoing major operations . More information about the role of shortened preoperative fasting in perioperative metabolism is needed for such elective minor/moderate abdominal procedures as laparoscopic cholecystectomy . We investigated the influence of a carbohydrate-rich drink given 2 h before laparoscopic cholecystectomy on insulin resistance and the metabolic response to trauma . Methods A group of 21 female c and i date s ( 18–65 years old ) for elective laparoscopic cholecystectomy were r and omized to either an 8 h fasting group ( control group : n = 10 ) or to a group receiving 200 ml of a carbohydrate beverage containing 12.5 % ( 25 g , 50 kcal per 100 ml and approximately 285 mOsm ) of maltodextrine 2 h before operation ( CHO group : n = 11 ) . Blood sample s for various biochemical assays were collected both at induction of anesthesia and after the 10th postoperative hour . Insulin resistance was assessed by the HOMA-IR equation ( Insulin ( μU/ml ) × blood glucose (mg/dl)/405 ) . Results There were no postoperative complications . Seventy percent ( 7/10 ) of the controls and 27.3 % ( 3/11 ) of the CHO group experienced at least one episode of vomiting ( RR = 2.42 , 95 % Confidence Interval [ CI ] = 0.88–6.68 ; P = 0.08 ) . Biochemical analysis showed that serum glucose ( P < 0.01 ) , insulin ( P < 0.01 ) , lactate/pyruvate ratio ( P = 0.03 ) , and triglycerides ( P < 0.01 ) for the control group were higher than for the CHO group . The value of HOMA-IR was significantly greater ( P = 0.03 ) in the conventionally fasted patients than in the CHO group . Conclusions Abbreviation of the period of preoperative fasting and administration of a carbohydrate beverage diminishes insulin resistance and the organic response to trauma PURPOSE : R and omized controlled trials have established that there is no benefit to withholding oral food and fluids from colorectal surgery patients postoperatively . The aim of this survey was to determine food preferences for the first postoperative meal and compare these with a traditional clear-fluid diet . METHODS : One hundred forty-five elective colorectal surgery patients were surveyed about their preferences for 35 common foods within 72 hours of surgery and their levels of nausea , hunger , and pain . Preferences were examined by postoperative day ( one vs. two ) and levels of nausea , hunger , and pain . RESULTS : The survey showed that patients significantly preferred solid foods as early as the first postoperative day and their preferences had little congruency with the traditional clear-fluid diet . Foods highest in preference , such as eggs , regular broth soup ( e.g. , chicken noodle soup ) , toast , and potatoes , were significantly more preferred than common clear-fluid diet items such as gelatin , clear broth , and carbonated beverages ( P < 0.01 ) . Oral supplements were preferred by only 44 % . Patients reported low levels of nausea , hunger , and pain . CONCLUSION : Postoperative colorectal surgery patients prefer to receive simple solid foods rather than a clear-fluid diet as their first postoperative meal Preoperative oral carbohydrate ( OCH ) reduces postoperative insulin resistance ( PIR ) . This r and omized trial investigated whether this effect is related to insulin‐induced activation of the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B ( PKB ) signalling pathway Objective : Currently most nutritional assessment techniques are based on their ability to predict clinical outcomes . However , the validity of any of these techniques to truly measure “ nutritional risk ” has not been proved . We have therefore prospect ively assessed the prognostic value of two nutritional assessment techniques and nonnutritional factors in determining outcome after major abdominal surgery . Methods : At admission and discharge , 100 patients undergoing major abdominal surgery were assessed on the following items : Subjective Global Assessment , Nutritional Risk Index , anthropometric measurements , serum total protein , serum albumin , lymphocyte count , total serum cholesterol . Patients were monitored for postoperative complications until death or discharge . Results : At admission , 44 % of the patients were malnourished according to the Subjective Global Assessment , while 61 % of the patients were malnourished according to the Nutritional Risk Index . At discharge , these numbers were 67 % and 82 % , respectively . Higher death rates were found in the malnourished groups . The risk of complication was increased in malnourished patients with both assessment techniques . The odds ratios for the association between malnutrition and complications varied between 1.926 and 9.854 with both assessment s. The presence of cancer in the patient was predictive for complication . Conclusions : Malnutrition is a marker of bad outcomes . Both Subjective Global Assessment and Nutritional Risk Index nutrition tests are predictive for malnutrition and postoperative complications in patients undergoing major abdominal surgery CONTEXT The impairment of insulin sensitivity , a marker of surgical stress , is important for outcomes . OBJECTIVE The aim was to assess the association between the quality of preoperative glycemic control , intraoperative insulin sensitivity , and adverse events after cardiac surgery . DESIGN AND SETTING We conducted a prospect i ve cohort study at a tertiary care hospital . SUBJECTS Nondiabetic and diabetic patients scheduled for elective cardiac surgery were included in the study . Based on their glycosylated hemoglobin A ( HbA(1c ) ) , diabetic patients were allocated to a group with good ( HbA(1c ) < 6.5 % ) or poor ( HbA(1c ) > 6.5 % ) glycemic control . INTERVENTION We used the hyperinsulinemic-normoglycemic clamp technique . MAIN OUTCOME MEASURES The primary outcome was insulin sensitivity measurement . Secondary outcomes were major complications within 30 d after surgery including mortality , myocardial failure , stroke , dialysis , and severe infection ( severe sepsis , pneumonia , deep sternal wound infection ) . Other outcomes included minor infections , blood product transfusions , and the length of intensive care unit and hospital stay . RESULTS A total of 143 nondiabetic and 130 diabetic patients were studied . In diabetic patients , a negative correlation ( r = -0.527 ; P < 0.001 ) was observed between HbA(1c ) and intraoperative insulin sensitivity . Diabetic patients with poor glycemic control had a greater incidence of major complications ( P = 0.010 ) and minor infections ( P = 0.006 ) . They received more blood products and spent more time in the intensive care unit ( P = 0.030 ) and the hospital ( P < 0.001 ) than nondiabetic patients . For each 1 mg x kg(-1 ) x min(-1 ) decrease in insulin sensitivity , the incidence of major complications increased ( P = 0.004 ) . CONCLUSIONS In diabetic patients , HbA(1c ) levels predict insulin sensitivity during surgery and possibly outcome . Intraoperative insulin resistance is associated with an increased risk of complications , independent of the patient 's diabetic state Background Overnight fasting is routine before elective surgery . This may not be the optimal way to prepare for surgical stress , however , because intravenous carbohydrate supplementation instead of fasting has recently been shown to reduce postoperative insulin resistance . In the current study , gastric emptying of a carbohydrate-rich drink was investigated before elective surgery and in a control situation . Methods Twelve patients scheduled for elective surgery were r and omly given 400 mL of either a carbohydrate-rich drink ( 285 mOsm/kg , 12.0 % carbohydrates , n = 6 ) or water 4 hours before being anesthetized . Gastric emptying was measured ( gamma camera , 99Tcm ) . Each patient repeated the protocol postoperatively as a control . All values were presented as the mean ± SEM by means of a nonparametric statistical evaluation . Results Despite the increased anxiety experienced by patients before surgery ( p < 0.005 ) , gastric emptying did not differ between the experimental and control situations . Initially , water emptied more rapidly than carbohydrate . However , after 90 minutes , the stomach was emptied regardless of the solution administered ( 3.2 ± 1.1 % [ mean ± SEM ] remaining in the stomach in the carbohydrate group versus 2.3 ± 1.2 % remaining in the stomach in the water group ) . Conclusions Preoperative anxiety does not prolong gastric emptying . The stomach had been emptied 90 minutes after Ingestion of both the carbohydrate-rich drink and water , thereby indicating the possibility of allowing an intake of iso-osmolar carbohydrate-rich fluids before surgery BACKGROUND The optimal target range for blood glucose in critically ill patients remains unclear . METHODS Within 24 hours after admission to an intensive care unit ( ICU ) , adults who were expected to require treatment in the ICU on 3 or more consecutive days were r and omly assigned to undergo either intensive glucose control , with a target blood glucose range of 81 to 108 mg per deciliter ( 4.5 to 6.0 mmol per liter ) , or conventional glucose control , with a target of 180 mg or less per deciliter ( 10.0 mmol or less per liter ) . We defined the primary end point as death from any cause within 90 days after r and omization . RESULTS Of the 6104 patients who underwent r and omization , 3054 were assigned to undergo intensive control and 3050 to undergo conventional control ; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients , respectively . The two groups had similar characteristics at baseline . A total of 829 patients ( 27.5 % ) in the intensive-control group and 751 ( 24.9 % ) in the conventional-control group died ( odds ratio for intensive control , 1.14 ; 95 % confidence interval , 1.02 to 1.28 ; P=0.02 ) . The treatment effect did not differ significantly between operative ( surgical ) patients and nonoperative ( medical ) patients ( odds ratio for death in the intensive-control group , 1.31 and 1.07 , respectively ; P=0.10 ) . Severe hypoglycemia ( blood glucose level , < or = 40 mg per deciliter [ 2.2 mmol per liter ] ) was reported in 206 of 3016 patients ( 6.8 % ) in the intensive-control group and 15 of 3014 ( 0.5 % ) in the conventional-control group ( P<0.001 ) . There was no significant difference between the two treatment groups in the median number of days in the ICU ( P=0.84 ) or hospital ( P=0.86 ) or the median number of days of mechanical ventilation ( P=0.56 ) or renal-replacement therapy ( P=0.39 ) . CONCLUSIONS In this large , international , r and omized trial , we found that intensive glucose control increased mortality among adults in the ICU : a blood glucose target of 180 mg or less per deciliter result ed in lower mortality than did a target of 81 to 108 mg per deciliter . ( Clinical Trials.gov number , NCT00220987 . HYPOTHESIS Immediate enteral feeding following major abdominal surgery reduces postoperative complications and mortality when compared with parenteral nutrition . DESIGN A prospect i ve multicenter r and omized trial . SETTING A university hospital department of digestive surgery . PATIENTS AND INTERVENTIONS Two hundred forty-one malnourished patients undergoing major elective abdominal surgery were r and omly assigned to receive , after surgery , either enteral ( enteral nutrition group : 119 patients ) or parenteral nutrition ( total parenteral nutrition group : 122 patients ) . The patients were monitored for postoperative complications and mortality . RESULTS The rate of major postoperative complications was similar in the enteral and parenteral groups ( enteral nutrition group : 37.8 % ; total parenteral nutrition group : 39.3 % ; P was not significant ) , as were the overall postoperative mortality rates ( 5.9 % and 2.5 % , respectively ; P was not significant ) . CONCLUSION The present study failed to demonstrate that enteral feeding following major abdominal surgery reduces postoperative complications and mortality when compared with parenteral nutrition BACKGROUND The provision of perioperative immune modulating enteral feeds after major surgery may result in reduced infective complications , but meta-analyses have not demonstrated a survival advantage . The aim of this study was to determine whether early postoperative immune modulating jejunostomy feeding results in reduced infective complications in patients undergoing resectional surgery for upper gastrointestinal cancer . METHODS A total of 120 patients undergoing resection for cancers of the pancreas , oesophagus and stomach were r and omized in a double-blind manner to receive jejunostomy feeding with an immune modulating diet ( Stresson-Group A ) or an isonitrogenous , isocaloric feed ( 1250 Calories and 75 g protein/l -- Nutrison High Protein-Group B ) for 10 - 15 days . Feeding was commenced 4h postoperatively and continued for 20 h/day . The target volume ( ml/h ) was 25 on day 0 , 50 on day 1 , and 75 thereafter . Outcome measures included complications , hospital stay and mortality . RESULTS A total of 108 patients ( 54 in each group ) were analysed . Feed delivery , although less than targeted , was similar in both groups . There were 6 ( 11 % ) deaths in each group . Median ( IQR ) postoperative hospital stay was 14.5 ( 12 - 23 ) days in Group A and 17.5 ( 13 - 23 ) days in Group B ( P=0.48 ) . A total of 24 ( 44 % ) patients in each group had infective complications ( P=1.0 ) . A total of 21 ( 39 % ) patients in Group A and 28 ( 52 % ) in Group B had non-infective complications ( P=0.18 ) . Jejunostomy-related complications occurred in 26 ( 48 % ) patients in Group A and 30 ( 56 % ) in Group B ( P=0.3 ) . CONCLUSION Early postoperative feeding with an immune modulating diet conferred no outcome advantage when compared with a st and ard feed BACKGROUND : Although hyperglycemia is a well-recognized risk factor in the context of cardiac surgery , the relevance of perioperative glycemic control for patients undergoing major noncardiac operations has received little attention . We design ed this study to assess the hyperglycemic response to liver resection , and to test the hypothesis that perioperative glucose and insulin administration while maintaining normoglycemia ( GIN therapy ) provides glycemic control superior to that achieved by the conventional use of insulin . METHODS : Patients were r and omly assigned to GIN therapy or st and ard therapy ( control group ) . In the GIN therapy group , insulin was administered at 2 mU · kg−1 · min−1 during surgery . At the end of surgery , the insulin infusion was decreased to 1 mU · kg−1 · min−1 and continued for 24 hours . Dextrose 20 % was infused at a rate adjusted to maintain blood glucose within the target range of 3.5 to 6.1 mmol · L−1 ( 63–110 mg · dL−1 ) . Patients in the st and ard therapy group received a conventional insulin sliding scale during and after surgery . The mean and SD of blood glucose as well as the percentage of blood glucose values within the target range were calculated . To evaluate intrasubject variability , the coefficient of variability ( CV ) of blood glucose was calculated for each patient . Episodes of severe hypoglycemia , i.e. , blood glucose < 2.2 mmol · L−1 ( 40 mg · dL−1 ) , were recorded . The primary outcome was the proportion of normoglycemic measurements . RESULTS : We studied 52 patients . The mean blood glucose value in patients receiving GIN therapy always remained within the target range . The blood glucose levels were lower in the GIN therapy group than in the st and ard therapy group ( during surgery , P < 0.01 ; after surgery , P < 0.001 ) . In nondiabetic patients receiving GIN therapy ( n = 19 ) , target glycemia was achieved in 90.1 % of the blood glucose measurements during surgery and in 77.8 % of the measurements after surgery . In diabetic patients receiving GIN therapy ( n = 7 ) , target glycemia was achieved in 81.2 % of the blood glucose measurements during surgery and in 70.5 % of the measurements after surgery . In nondiabetic patients receiving st and ard therapy ( n = 19 ) , target glycemia was achieved in 37.4 % of the blood glucose measurements during surgery and in 18.3 % of the measurements after surgery . In diabetic patients receiving st and ard therapy ( n = 7 ) , target glycemia was achieved in 4.3 % of the blood glucose measurements during surgery and in 2.9 % of the measurements after surgery . The SD and CV of blood glucose were smaller in the GIN therapy group than in the st and ard therapy group , especially in nondiabetic patients after surgery ( SD , P < 0.001 ; CV , P = 0.027 ) . No patients receiving GIN therapy experienced severe hypoglycemia during surgery . One patient receiving GIN therapy experienced hypoglycemia in the intensive care unit after surgery without neurological sequelae . CONCLUSIONS : GIN therapy effectively provides normoglycemia in patients undergoing liver resection ( clinical trials.gov , NCT00774098 ) OBJECTIVE To assess the effect of an intensive glucose management protocol in a heterogeneous population of critically ill adult patients . PATIENTS AND METHODS This study consisted of 800 consecutive patients admitted after institution of the protocol ( treatment group , between February 1 , 2003 , and January 10 , 2004 ) and 800 patients admitted immediately preceding institution of the protocol ( baseline group , between February 23 , 2002 , and January 31 , 2003 ) . The setting was a 14-bed medical-surgical intensive care unit ( ICU ) in a university-affiliated community teaching hospital . The protocol involved intensive monitoring and treatment to maintain plasma glucose values lower than 140 mg/dL. Continuous intravenous insulin was used if glucose values exceeded 200 mg/dL on 2 successive occasions . RESULTS The 2 groups of patients were well matched , with similar age , sex , race , prevalence of diabetes mellitus , Acute Physiology and Chronic Health Evaluation II scores , and distribution of diagnoses . After institution of the protocol , the mean glucose value decreased from 152.3 to 130.7 mg/dL ( P<.001 ) , marked by a 56.3 % reduction in the percentage of glucose values of 200 mg/dL or higher , without a significant change in hypoglycemia . The development of new renal insufficiency decreased 75 % ( P=-.03 ) , and the number of patients undergoing transfusion of packed red blood cells decreased 18.7 % ( P=.04 ) . Hospital mortality decreased 29.3 % ( P=.002 ) , and length of stay in the ICU decreased 10.8 % ( P=.01 ) . CONCLUSION The protocol result ed in significantly improved glycemic control and was associated with decreased mortality , organ dysfunction , and length of stay in the ICU in a heterogeneous population of critically ill adult patients . These results support the adoption of this low-cost intervention as a st and ard of care for critically ill patients Background : Esophagectomy represents an exemplar of controlled major trauma , with marked metabolic , immunologic , and physiologic changes as well as an associated high incidence of complications . Eicosapentaenoic acid ( EPA ) enriched enteral nutrition ( EN ) modulates immune function and limits catabolism in patients with advanced cancer , but its impact in the peri-operative period is unclear . Objectives : To examine the effects of perioperative EPA enriched EN on the metabolic , nutritional , and immuno-inflammatory response to esophagectomy , and on postoperative complications . Methods : In a double-blind design , patients were r and omized to a st and ard EN formula or a formula enriched with 2.2 g EPA/d for 5 days preoperatively ( orally ) and 21 days postoperatively ( jejunostomy ) . Segmental bioelectrical impedance analysis was performed preoperatively and on POD 21 . Postoperative complications were monitored , as well as the acute phase response , coagulation markers , and serum cytokines . Results : Fifty-three patients ( 28 EPA , 25 st and ard ) completed the study , and both groups were well matched . Serum and peripheral blood mononuclear cell ( P BMC ) membrane EPA levels were significantly increased in the EPA group . There was no difference in the incidence of major complications . The EPA group maintained all aspects of body composition postoperatively , whereas patients in the st and ard EN group lost significant amounts of fat-free mass ( 1.9 kg , P = 0.030 ) compared with the EPA group [ leg ( 0.3 kg , P = 0.05 ) , arm ( 0.17 kg , P = 0.01 ) , and trunk ( 1.44 kg , P = 0.03 ) ] . The EPA group had a significantly ( P < 0.05 ) attenuated stress response for TNFα , IL-10 , and IL-8 compared with the st and ard group . Conclusions : EPA supplemented early EN is associated with preservation of lean body mass post esophagectomy compared with a st and ard EN . These properties may merit longer-term study to address its impact on recovery of function and quality of life in models of complex surgery or multimodal cancer treatment regimens AIM To evaluate the nutritional risk of patients with gastric carcinoma using the method ologies of European Nutritional Risk Screening 2002 ( NRS 2002 ) and its relationship with postoperative results . METHODS We prospect ively evaluated the nutritional risk of 314 cases of gastric carcinoma patients in one center from 2004 to 2007 with NRS 2002 , in accordance with China 's normal body mass index ( BMI ) , and observed its relationship with postoperative complications , mortality and length of hospital stay . RESULTS Of 337 cases , 314 ( 93.1 % ) were suitable for assessment by NRS 2002.The number of patients with a score > or = 3 was 125 before operation , comprising 39.8 % of patients with gastric carcinoma . The rate of complications ( 26.2 % ) of the preoperative nutritional risk group ( NRS 2002 score > or = 3 ) was higher than those in the preoperative nutritional normal group ( NRS 2002 score < 3 ) ( P < 0.05 ) . Assessed by multivariate logistics regression analysis , the odds ratio of developing complications was 2.366 ( P < 0.05 ) and 2.277 ( P < 0.05 ) by NRS 2002 score and clinicopathological stage , respectively . The correlation between length of hospital stay and nutritional risk was also assessed by Pearson correlation analysis . The Pearson coefficient was 0.177 ( P = 0.002 ) . CONCLUSION Preoperative nutrition score ( NRS 2002 ) > or = 3 predicted more postoperative complications and longer length of hospital stay . It indicated that preoperative nutritional support was necessary in patients with a preoperative nutritional score ( NRS 2002 ) > or = 3 Objective : The aim of this trial was to investigate whether a routine of allowing normal food at will increases morbidity after major upper gastrointestinal ( GI ) surgery . Summary Background Data : Nil-by-mouth with enteral tube feeding is widely practice d for several days after major upper GI surgery . After other abdominal operations , normal food at will has been shown to be safe and to improve gut function . Methods : Patients were r and omly assigned to a routine of nil-by-mouth and enteral tube feeding by needle-catheter jejunostomy ( ETF group ) or normal food at will from the first day after major upper GI surgery . Primary end point was rate of major complications and death . Secondary outcomes were minor complications and adverse events , bowel function , and length of stay . All patients were invited to a follow-up at 8 weeks after discharge from the hospital . Results : Four hundred fifty-three patients who underwent major open upper GI surgery in 5 centers were enrolled between 2001 and 2006 . Four hundred forty-seven patients were correctly r and omized . Of 227 patients 76 ( 33.5 % ) had major complications in the ETF group compared with 62 ( 28.2 % ) of 220 patients allowed normal food at will ( P = 0.26 , 95 % CI for the difference in rate from −3.3 to 13.9 ) . In the ETF group , 36 ( 15.9 % ) patients were reoperated compared with 29 ( 13.2 % ) in the group allowed normal food at will ( P = 0.50 ) and 30-day mortality was 10 ( 4.4 % ) of 227 and 11 ( 5.0 % ) of 220 patients , respectively ( P = 0.83 ) . Time to resumed bowel function was significantly in favor of allowing normal food at will ( P = 0.01 ) , as were the total number of major complications , length of stay , and rate of postdischarge complications . Conclusions : Allowing patients to eat normal food at will from the first day after major upper GI surgery does not increase morbidity compared with traditional care with nil-by-mouth and enteral feeding HYPOTHESIS Perioperative administration of a supplemented enteral formula may decrease postoperative morbidity . DESIGN R and omized clinical trial . SETTING Department of surgery at a university hospital . PATIENTS One hundred ninety-six registered malnourished patients ( weight loss > or = 10 % ) who were c and i date s for major elective surgery for malignancy of the gastrointestinal tract . INTERVENTION After r and omization ( n = 150 ) , one group received postoperative enteral feeding with a st and ard diet within 12 hours of surgery ( control group ; n = 50 ) . Another group orally received 1 L/d for 7 consecutive days of a liquid diet enriched with arginine , omega-3 fatty acids , and RNA ( preoperative group ; n = 50 ) . After surgery , patients were given the same st and ard enteral formula as the control group . A third group orally received 1 L/d for 7 consecutive days of the enriched liquid diet . After surgery , patients were given enteral feeding with the same enriched formula ( perioperative group ; n = 50 ) . MAIN OUTCOME MEASURES Postoperative complications and length of hospital stay . RESULTS The 3 groups were comparable for baseline demographics , biochemical markers , comorbidity factors , and surgical variables . The intent-to-treat analysis showed that the total number of patients with complications was 24 in the control group , 14 in the preoperative group , and 9 in the perioperative group ( P = .02 , control group vs perioperative group ) . Postoperative length of stay was significantly shorter in the preoperative ( 13.2 days ) and perioperative ( 12.0 days ) groups than in the control group ( 15.3 days ) ( P = .01 and P = .001 , respectively , vs the control group ) . CONCLUSION Perioperative immunonutrition seems to be the best approach to support malnourished patients with cancer OBJECTIVE To determine if parenteral glutamine dipeptide supplementation given only in the preoperative period in malnourished patients after gastrointestinal surgery would sustain its effects into the first postoperative week , as shown by immune indices . METHODS A prospect i ve r and omized study on malnourished adult patients for abdominal surgery was done where one group ( n = 17 ) received preoperative glutamine supplementation ( 0.3 g . kg(-1 ) x d(-1 ) ) for 5 d and the other ( n = 17 ) had none . Both received isocaloric ( 30 kcal x kg(-1 ) x d(-1 ) ) and isonitrogenous ( 1.5 g x kg(-1 ) x d(-1 ) ) nutrition . Outcomes were 1 ) immune indices on admission ( day 1 ) , the day before surgery ( day 2 ) , and the seventh postoperative day ( day 3 ) ; and 2 ) clinical outcomes were infection , wound complication , days in the intensive care unit , and mortality . Statistical tests were repeated sample s analysis of variance , Friedman 's test , Wilcoxon 's test , and t test for individual comparison . RESULTS The glutamine-supplemented group showed an increase in total white blood cells ( from 8700 on day to 11 080 on day 2 , P = 0.026 ) , granulocytes ( from 6177 on day 1 to 8568 on day 2 , P = 0.039 ) , and lymphocytes ( from 1516 on day 1 to 1747 on day 2 , P = 0.049 ) . Significant decreases in glutamine-supplemented group values from day 2 to day 3 occurred in granulocytes , lymphocytes , and CD8 , CD22 , and CD19 cells . Clinical outcome was similar in both groups . Intake was adequate in both groups ( preoperative 85 % versus postoperative 82 % computed ) and the mean glutamine delivered was 18 g/d . CONCLUSION Parenteral glutamine supplementation in the preoperative period result ed in increased white blood cell , granulocyte , and lymphocyte counts , which was not sustained in the first week of the postoperative period , when supplementation was discontinued before surgery BACKGROUND We undertook this study to test the hypothesis that perioperative total parenteral nutrition ( TPN ) decreases the incidence of serious complications after major abdominal or thoracic surgical procedures in malnourished patients . METHODS We studied 395 malnourished patients ( 99 percent of them male ) who required laparotomy or noncardiac thoracotomy . They were r and omly assigned to receive either TPN for 7 to 15 days before surgery and 3 days afterward ( the TPN group ) or no perioperative TPN ( the control group ) . The patients were monitored for complications for 90 days after surgery . RESULTS The rates of major complications during the first 30 days after surgery in the two groups were similar ( TPN group , 25.5 percent ; control group , 24.6 percent ) , as were the overall 90-day mortality rates ( 13.4 percent and 10.5 percent , respectively ) . There were more infectious complications in the TPN group than in the controls ( 14.1 vs. 6.4 percent ; P = 0.01 ; relative risk , 2.20 ; 95 percent confidence interval , 1.19 to 4.05 ) , but slightly more noninfectious complications in the control group ( 16.7 vs. 22.2 percent ; P = 0.20 ; relative risk , 0.75 ; 95 percent confidence interval , 0.50 to 1.13 ) . The increased rate of infections was confined to patients categorized as either borderline or mildly malnourished , according to Subjective Global Assessment or an objective nutritional assessment , and these patients had no demonstrable benefit from TPN . In contrast , severely malnourished patients who received TPN had fewer noninfectious complications than controls ( 5 vs. 43 percent ; P = 0.03 ; relative risk , 0.12 ; 95 percent confidence interval , 0.02 to 0.91 ) , with no concomitant increase in infectious complications . CONCLUSIONS The use of preoperative TPN should be limited to patients who are severely malnourished unless there are other specific indications |
12,989 | 21,627,463 | Smoking has a negative effect on bone regeneration after periodontal treatment .
Patients should be advised that their smoking habit may result in poorer bone regeneration after periodontal treatment | BACKGROUND The effect of smoking on soft tissues after periodontal treatment has been extensively studied .
However , little focus has been placed on the impact of smoking on bone regeneration after treatment .
The aim of this review is to systematic ally assess the effect of smoking on bone regeneration after periodontal treatment . | To investigate the relationship of smoking with the rate of pseudarthrosis ( surgical nonunion ) , 50 patients , who were smokers , and 50 patients , who were not , and who had had a two-level laminectomy and fusion during 1977 and 1978 were r and omly selected for this study . Most of those participating had sustained job-related injuries whereas the others had no common etiology for their back dysfunction . Most of the patients were from the southeastern United States . Ages ranged from 23 to 62 years , with a mean age of 42.4 years for smokers and 42.7 years for nonsmokers . There was an equal representation of males and females , with minorities represented according to their general percentage in the population . Examination 1 to 2 years after surgery revealed that 40 % ( 20 ) of the smokers had developed a pseudarthrosis , whereas among nonsmokers , the rate was 8 % ( 4 ) . This finding appears to be independent of age , sex , or race and was statistically significant ( χ2=14.035 , p=.001 ) . It was hypothesized that the higher incidence of surgical nonunion among smokers may be related to blood gas levels . Nonsmokers showed no significant deficiencies , whereas smokers showed a mean PO2 level of 78.5 % ( normal=95 - 97 ) and a mean O2 saturation level of 92.9 % ( normal=95 or above ) . Implication s and suggestions for further research are also discussed The aim of this controlled , clinical study was to evaluate guided tissue regeneration using a bioabsorbable membrane in periodontal intraosseous defects . Forty patients , each contributing one defect > or = 4 mm in depth participated . The control group ( 18 individuals ) received conventional flap therapy , while the test group ( 22 individuals ) was treated using the bioabsorbable membrane , Guidor . Clinical assessment s were made by one examiner , blinded with respect to treatment group , at baseline , 6 and 12 months following surgery . Baseline probing pocket depths of 7.7+/-1.4 mm in the membrane group and 7.6+/-1.9 mm in the control group were measured . Twelve month results showed a significant clinical attachment level gain in both control ( 1.1+/-1.8 mm ) , and membrane group ( 1.3+/-2.1 mm ) . Probing pocket depth reduction of 2.6+/-1.9 mm and 2.7+/-1.9 mm was observed in the respective groups . Bone sounding showed a non-significant gain of 0.4+/-1.8 mm and 0.6+/-1.4 mm at membrane and control sites , respectively . Radiographic evaluation confirmed these results . There were no significant differences found between treatment groups for any of the tested variables . Smoking had a negative effect on healing in both groups . In conclusion , clinical and radiographic results indicate that guided tissue regeneration using a bioabsorbable membrane at intraosseous defects did not predictably achieve greater clinical attachment level gain nor bone gain when compared to conventional flap therapy We retrospectively review ed a prospect ively followed cohort of 105 patients with 110 open tibia fractures treated with external fixator or intramedullary nail to determine whether smoking affects fracture healing . Severe open tibia-shaft fractures treated at a tertiary-care medical center were included . Patients with type II , IIIA , or IIIB tibia fractures were eligible . Treatment for all patients was similar , except that they were r and omized to receive external fixator or intramedullary nail . Time to fracture healing was the main outcome measurement . Smokers had a union rate of 84 % ( 52/62 ) , and nonsmokers had a union rate of 94 % ( 45/48 ) , P = .10 . For smokers in one arm of the study , time to union was significantly longer ( P = .01 ) , and there were more complications ( P = .04 ) . Smoking decreased unions , slowed healing , and increased complications Objectives : Current data show smoking is associated with a number of complications of the fracture healing process . A concern , however , is the potential confounding effect of covariates associated with smoking . The present study is the first to prospect ively examine time to union , as well as major complications of the fracture healing process , while adjusting for potential confounders . Setting : Eight Level I trauma centers . Patients : Patients with unilateral open tibia fractures were divided into 3 baseline smoking categories : never smoked ( n = 81 ) , previous smoker ( n = 82 ) , and current smoker ( n = 105 ) . Outcome Measure : Time to fracture healing , diagnosis of infection , and osteomyelitis . Methods : Survival and logistic analyses were used to study differences in time to fracture healing and the likelihood of developing complications , respectively . Multivariate models were used to adjust for injury severity , treatment variations , and patient characteristics Results : After adjusting for covariates , current and previous smokers were 37 % ( P = 0.01 ) and 32 % ( P = 0.04 ) less likely to achieve union than nonsmokers , respectively . Current smokers were more than twice as likely to develop an infection ( P = 0.05 ) and 3.7 times as likely to develop osteomyelitis ( P = 0.01 ) . Previous smokers were 2.8 times as likely to develop osteomyelitis ( P = 0.07 ) , but were at no greater risk for other types of infection . Conclusion : Smoking places the patient at risk for increased time to union and complications . Previous smoking history also appears to increase the risk of osteomyelitis and increased time to union . The results highlight the need for orthopaedic surgeons to encourage their patients to enter a smoking cessation programs The aim of the present clinical trial was to evaluate the effect of different modes of periodontal therapy on patients with moderately advanced periodontal disease and to express the findings in terms of probing pocket depth and attachment level alterations at periodontal sites with different initial probing depths . The material consisted of 16 patients , 35 - 65 years of age . Following a Baseline examination including assessment s of oral hygiene status , gingival conditions , probing pocket depths and probing attachment levels , the patients were subjected to periodontal treatment . A " split-mouth " design approach of therapy was used and the jaw quadrants were r and omly selected for the following different treatment procedures : ( 1 ) scaling and root planning , ( 2 ) scaling and root planing in conjunction with a gingivectomy procedure , ( 3 ) scaling and root planing in conjunction with an apically repositioned flap procedure without bone recontouring , ( 4 ) scaling and root planing in conjunction with an apically repositioned flap procedure including bone recontouring , ( 5 ) scaling and root planing in conjunction with a modified Widman flap procedure without bone recontouring and ( 6 ) scaling and root planing in conjunction with a modified Widman flap procedure including bone recontouring . The patients were following active treatment enrolled in a supervised maintenance care program including " professional tooth cleaning " once every 2 weeks during a 6-month period of healing , after which a final examination was performed . The investigation demonstrated that active therapy including meticulous subgingival debridement result ed in a low frequency of gingival sites which bled on probing , a high frequency of sites with shallow pockets ( less than 4 mm ) and the disappearance of pockets with a probing depth of greater than 6 mm . Between the Baseline examination and the 6-month re-examination , the probing attachment level for initially shallow pockets remained basically unaltered , but with a tendency of a minor apical shift . This occurred in all 6 treatment groups . For sites with initial probing depths of 4 - 6 mm and greater than 6 mm , there was in all groups some gain of probing attachment . This gain was most pronounced in the initially deeper ( greater than 6 mm ) pockets . With the use of regression analysis , the " critical probing depth " ( CPD ) value ( i.e. the initial probing depth value below which loss of attachment occurred as a result of treatment and above which gain of probing attachment level result ed ) was calculated for each of the 6 methods of treatment used . A comparison of the CPD-values between the 6 treatment groups did not reveal any major differences OBJECTIVES Current literature is ambivalent on the use of barrier membranes for regeneration of intraosseous defects . One of the reasons for unpredictable results may be related to infection before , during and after the surgical procedure . Therefore , the purpose of the present controlled study was to evaluate both the use of membranes ( MEM ) and antibiotics ( AB ) , separately and in combination . METHODS In all , 25 patients with two intraosseous periodontal defects each were r and omized in two groups : AB+ group receiving systemic antibiotics ( n = 13 ) and AB- group without antibiotics ( n = 12 ) . After raising flaps and after debridement , both defects in each patient were covered by a bioresorbable membrane ( MEM+ ) . However , just before suturing the flaps in a coronal position , the membrane over one of the two defects was removed at r and om ( MEM- ) . This protocol result ed in four groups of defects : ( i ) . MEM- AB- ; ( ii ) . MEM+ AB- ; ( iii ) . MEM- AB+ ; ( iv ) . MEM+ AB+ . Patients were monitored clinical ly and microbiologically for 1 year . Data were analyzed in repeated measures ancova 's and adjusted means for clinical variables were obtained from the final statistical model . RESULTS Reduction in probing pocket depth ( PPD ) at 12 months postoperatively varied between 2.54 and 3.06 mm between the four treatment modalities , but overall no main effect of MEM or AB was found . Gains in probing attachment level ( PAL ) at 12 months postoperatively varied between 0.56 and 1.96 mm for the 4 treatments . In the overall analysis for PAL , no main effect of MEM or AB was found . Gains in probing bone level ( PBL ) 12 months postoperatively ranged from 1.39 to 2.09 mm between the treatment groups . Again , overall , no main effects of MEM or AB were found for PBL . Explorative statistical analyses indicated that smoking and not MEM or AB is a determining factor for gain in PBL ( P = 0.0009 ) . Nonsmokers were estimated to gain 2.04 mm PBL compared to 0.52 mm in smokers . The prevalence of several periodontal pathogens , at the day of surgery or postoperatively , and specific defect characteristics , were not determining factors for gain in PAL and PBL . CONCLUSIONS Neither the application of barrier membranes nor the use of systemic antibiotics showed an additional effect over control on both soft and hard tissue measurements in the treatment of intraosseous defects . In contrast , smoking was a determining factor severely limiting gain in PBL in surgical procedures aim ed at regeneration of intraosseous defects The role of smoking as a risk factor for periodontitis was assessed separately in diabetic and nondiabetic study groups . Subject listings stratified for age ( 19 to 40 years ) and sex were obtained for subjects with insulin-dependent diabetes mellitus ( IDDM ) and nondiabetic subjects . For both the IDDM group ( n = 132 ) and the nondiabetic group ( n = 95 ) , age and sex stratified sample s were constructed by r and om selection of subjects from each subject listing . Patients were recruited by phone , examined , and their medical and dental histories obtained . Among nondiabetic subjects , the prevalence of periodontitis was markedly higher among current smokers compared with never smokers ( P < or = 0.005 ) in both the 19 to 30 year-old ( 46 % vs. 12 % ) and 31 to 40 year-old groups ( 88 % vs. 33 % ) . The subject mean percent of sites with gingival pocket depth > or = 4 mm was higher among current smokers than never smokers ( P = 0.001 ) in the 19 to 30 ( 8.2 % vs. 3.4 % ) and 31 to 40 ( 14.3 % vs. 4.3 % ) age groups . The effects of smoking among IDDM subjects were similar to that observed in the nondiabetic population . There were no differences between current and never smokers in the proportion of sites positive for plaque . Attributable risk percents from prevalence data suggest that among nondiabetic subjects , a large proportion , perhaps as much as 51 % of the periodontitis in the 19 to 30 year old group and 32 % of the periodontitis in the 31 to 40 year old group , is associated with smoking . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND The purpose of this r and omized , controlled , blinded , clinical investigation was to determine the effect of postsurgical antibiotics on osseous healing in Class II furcation defects . METHODS Twenty-four Class II furcation defects in 24 patients were treated with either a polylactide bioabsorbable membrane , demineralized freeze-dried bone allograft ( DFDBA ) plus antibiotics ( GBA or test group ) or with a polylactide membrane and DFDBA alone ( GB or control group ) . Twelve patients were included in each group . The antibiotic regimen consisted of ciprofloxacin 250 mg twice daily and metronidazole 250 mg tid for 1 week followed by a 7-week regimen of doxycycline hyclate 50 mg daily . Treatment was performed on either m and ibular buccal or lingual , or maxillary buccal Class II furcation defects . Defects were r and omly selected by a coin toss for treatment and all open and closed measurements were performed by a blinded examiner . Final open and closed measures from a stent were repeated at the 9-month second stage surgery . Power analysis to determine superiority of antibiotic treatment showed that a 12 per group sample size would yield 93 % power to detect a 1.5 mm difference and 64 % power to detect a 1 mm difference . RESULTS Mean open horizontal probing depth reductions at 9 months were greater for the GBA group than for the GB group ( 2.92+/-1.78 versus 2.50+/-1.62 mm ) ; however , these differences were not statistically significant . Seven of 12 furcations ( 58 % ) in the GBA group demonstrated > 50 % vertical defect fill at 9 months compared to 8 of 12 furcations ( 67 % ) in the GB group . There were no significant differences in mean open horizontal probing depth reduction between smokers and non-smokers in either the GBA or GB groups . Membrane exposure did not appear to affect regenerative healing in either the GBA or GB groups . CONCLUSIONS The administration of postsurgical antibiotics did not produce statistically superior osseous healing of Class II furcation defects . This result may be attributable to membrane design which facilitates connective tissue ingrowth , thereby preventing bacterial downgrowth and contamination of the newly regenerated tissues The present study evaluated clinical ly and radiographically the short-term results of the healing of infrabony defects at maxillary premolars treated according to guided tissue regeneration ( GTR ) . 9 patients with bilateral presence of infrabony defects with or without furcation involvements at maxillary premolars were selected . At baseline assessment s of plaque and gingival indices , bleeding , probing pocket depth and attachment level , and furcation measurements were recorded . Conventional radiographs were obtained in a way that assured a reproducible projection geometry . One premolar was r and omly treated with GTR and the contralateral with open debridement . Clinical and radiographic examinations were performed again 6 months postoperatively . The bone tissue changes were assessed by means of conventional radiographs and subtraction images . Sites treated by both procedures demonstrated an improvement of gingival conditions and a reduction of pocket depths . A statistically significant attachment gain was obtained for the test ( mean 1.2 mm ) , but not for the control sites ( mean 0.6 mm ) . The differences , though , were not significant between the test and control sites . Limited improvement in furcation closure was recorded . The radiographic examination demonstrated loss of bone tissue in four sites treated with GTR . The findings suggest that the regeneration of the periodontal soft and bone tissues was not significantly enhanced with the GTR therapy This study evaluated a bioresorbable barrier with and without decalcified freeze-dried bone allograft ( DFDBA ) in the treatment of human molar furcations . 14 subjects with paired class II m and ibular molar furcation defects participated in the study ( 8 male and 6 female ) . The class-II furcation defects were r and omly treated with either the resorbable barrier alone or resorbable barrier in combination with decalcified freeze-dried bone allograft ( DFDBA ) . Gingival recession , probing depth , clinical attachment , and bone fill were measured 6 months post-treatment measurements were repeated and each site was surgically re-entered . When the resorbable barrier alone was compared to resorbable barrier in combination with DFDBA , probing depth reduction was significantly ( p < 0.01 ) in favor of the combination therapy . Vertical bone gain was significant with the combination treatment demonstrating more bone fill ( p < 0.02 ) . Smoking was also a variable examined in this study . When compared to smokers , non-smokers for both treatment groups revealed greater probing depth reduction , vertical bone gain , and horizontal bone gain . Within the non-smoking group , probing depth reduction was also significantly higher for the resorbable barrier and DFDBA group than the resorbable alone group ( p < 0.02 ) . These results illustrate that the probing depth reduction is better in the non-smoker and the best in the non-smoker with the combination therapy of resorbable barrier and DFDBA than with resorbable barrier alone Patients admitted to the School of Dentistry , Stockholm , for treatment of chronic periodontal disease during the years 1980 - 82 were retrospectively investigated with respect to their smoking habits . The investigation was design ed as a case control study and covered all patients 30 , 40 , or 50 yr of age upon admission , in all 155 . As control served a r and om sample of the Stockholm population . The periodontal variables under scrutiny were frequency of periodontally diseased teeth , frequency of periodontally diseased sites ( probing depth greater than 4 mm ) , gingival index , and plaque index . The overall occurrence rate of smokers in the sample of cases was 56 % , which is significantly greater than the population at large . This held true for all three age cohorts and for men as well as women . The risk ratio was 2.5 , indicating more prevalent disease among smokers . Further , significantly greater frequencies of periodontally involved teeth and diseased sites were found in smokers , indicating more severe disease among smokers . Gingival index and plaque index did not notably differ between smoking groups . The results suggest increased prevalence as well as severity in smokers . Smoking , therefore , should be considered a risk factor for chronic periodontal disease BACKGROUND Growth factors are generally accepted to be essential mediators of tissue repair via well-established mechanisms of action that include stimulatory effects on angiogenesis and cellular proliferation , ingrowth , differentiation , and matrix bio synthesis . The aim of this study was to evaluate in a large-scale , prospect i ve , blinded , and r and omized controlled clinical trial the safety and effectiveness of purified recombinant human platelet-derived growth factor ( rhPDGF-BB ) mixed with a synthetic beta-tricalcium phosphate ( beta-TCP ) matrix for the treatment of advanced periodontal osseous defects at 6 months of healing . METHODS Eleven clinical centers enrolled 180 subjects , each requiring surgical treatment of a 4 mm or greater intrabony periodontal defect and meeting all inclusion and exclusion criteria . Subjects were r and omized into one of three treatment groups : 1 ) beta-TCP + 0.3 mg/ml rhPDGF-BB in buffer ; 2 ) beta-TCP + 1.0 mg/ml rhPDGF-BB in buffer ; and 3 ) beta-TCP + buffer ( active control ) . Safety data were assessed by the frequency and severity of adverse events . Effectiveness measurements included clinical attachment levels ( CAL ) and gingival recession ( GR ) measured clinical ly and linear bone growth ( LBG ) and percent bone fill ( % BF ) as assessed radiographically by an independent central ized radiology review center . The area under the curve ( AUC ) , an assessment of the rate of healing , was also calculated for CAL measurements . The surgeons , clinical and radiographic evaluators , patients , and study sponsor were all masked with respect to treatment groups . RESULTS CAL gain was significantly greater at 3 months for group 1 ( rhPDGF 0.3 mg/ml ) compared to group 3 ( beta-TCP + buffer ) ( 3.8 versus 3.3 mm ; P = 0.032 ) , although by 6 months , this finding was not statistically significant ( P = 0.11 ) . This early acceleration of CAL gain led to group 1 exhibiting a significantly greater rate of CAL gain between baseline and 6 months than group 3 as assessed by the AUC ( 68.4- versus 60.1-mm weeks ; P = 0.033 ) . rhPDGF ( 0.3 mg/ml)-treated sites also had significantly greater linear bone gain ( 2.6 versus 0.9 mm , respectively ; P < 0.001 ) and percent defect fill ( 57 % versus 18 % , respectively ; P < 0.001 ) than the sites receiving the bone substitute with buffer at 6 months . There was less GR at 3 months in group 1 compared to group 3 ( P = 0.04 ) ; at 6 months , GR for group 1 remained unchanged , whereas there was a slight gain in gingival height for group 3 result ing in comparable GR . There were no serious adverse events attributable to any of the treatments . CONCLUSIONS To our knowledge , this study is the largest prospect i ve , r and omized , triple-blinded , and controlled pivotal clinical trial reported to date assessing a putative periodontal regenerative and wound healing therapy . The study demonstrated that the use of rhPDGF-BB was safe and effective in the treatment of periodontal osseous defects . Treatment with rhPDGF-BB stimulated a significant increase in the rate of CAL gain , reduced gingival recession at 3 months post-surgery , and improved bone fill as compared to a beta-TCP bone substitute at 6 months AIM The purpose of this study was to assess the healing response of intrabony defects following regenerative treatment with platelet-rich plasma ( PRP ) combined with a bovine-derived xenograft ( BDX ) in smokers and non-smokers . MATERIAL S AND METHODS A total of 24 advanced chronic periodontitis patients , 12 smokers and 12 non-smokers , with 113 intrabony defects with an intrabony component of or /=3 mm were included in this study . Defects were surgically treated with PRP/BDX . At baseline and 12 months after surgery , the following parameters were recorded : plaque and sulcus bleeding indices , probing depth ( PD ) , relative attachment level , marginal recession , probing and radiographic bone levels . RESULTS Considering the soft tissue measurements , smokers and non-smokers presented a mean PD reduction of 3.97 + /- 0.76 and 4.63 + /- 0.52 mm , recession of 0.76 + /- 0.44 and 0.50 + /- 0.12 mm and attachment gain of 3.26 + /- 0.42 and 4.06 + /- 0.40 mm , respectively . Evaluation of the hard tissue findings revealed that the mean clinical and radiographic bone gains in smokers and non-smokers were 2.83 + /- 0.47 and 3.63 + /- 0.38 mm , 2.98 + /- 0.38 and 3.67 + /- 0.48 mm , respectively . Inter-group differences for PD reduction ( p<0.05 ) , attachment ( p<0.001 ) , clinical ( p<0.001 ) and radiographic bone gains ( p<0.001 ) were found to be significant between smokers and non-smokers . CONCLUSIONS Within the limits of this study , the results indicate that treatment outcome following PRP/BDX application in intrabony defects is impaired with smoking BACKGROUND , AIMS The aim of this double-blind , parallel study was to evaluate the adjunctive effects of systemically administered amoxicillin and metronidazole in a group of adult periodontitis patients who also received supra- and subgingival debridement . METHODS 49 patients with a diagnosis of generalised severe periodontitis participated in the study . R and om assignment result ed in 26 patients in the placebo ( P ) group with a mean age of 40 years and 23 patients in the test ( T ) group which had a mean age of 45 years . Clinical measurements and microbiological assessment s were taken at baseline and 3 months after completion of initial periodontal therapy with additional placebo or antibiotic treatment . Patients received coded study medication of either 375 mg amoxicillin in combination with 250 mg metronidazole or identical placebo tablets , every 8 hours for the following 7 days . RESULTS At baseline , no statistically significant differences between groups were found for any of the clinical parameters . Except for the plaque , there was a significantly larger change in the bleeding , probing pocket depth ( PPD ) and clinical attachment level ( CAL ) in the T-group as compared to the P-group after therapy . The greatest reduction in PPD was found at sites with initial PPD of > or = 7 mm , 2.5 mm in the P-group and 3.2 mm in the T-group . The improvement in CAL was most pronounced in the PPD category > or = 7 mm and amounted to 1.5 mm and 2.0 mm in the P- and T-groups , respectively . No significant decrease was found in the number of patients positive for any of the test species in the P-group . The number of patients positive for Porphyromonas gingivalis , Bacteroides forsythus and Prevotella intermedia in the T-group showed a significant decrease . After therapy there was a significant difference between the P- and the T- group in the remaining number of patients positive for P. gingivalis , B. forsythus and Peptostreptococcus micros . 4 subgroups were created on the basis of the initial microbiological status for P. gingivalis positive ( Pg-pos ) and negative patients ( Pg-neg ) in the P- and the T-groups . The difference in reduction of PPD between Pg-pos and Pg-neg patients was particularly evident with respect to the changes in % of sites with a probing pocket depth > or = 5 mm . This % decreased from 45 % at baseline to 23 % after treatment in the Pg-pos placebo subgroup and decreased from 46 % to 11 % in the Pg-pos test subgroup ( p < or = 0.005 ) . In contrast , the changes in the proportions of sites with a probing pocket depth > or = 5 mm in the Pg-neg placebo and Pg-neg test subgroup were similar , from 43 % at baseline to 18 % after treatment versus 40 % to 12 % respectively . CONCLUSIONS This study has shown that systemic usage of metronidazole and amoxicillin , when used in conjunction with initial periodontal treatment in adult periodontitis patients , achieves significantly better clinical and microbiological results than initial periodontal treatment alone . Moreover , this research suggests that especially patients diagnosed with P. gingivalis benefit from antibiotic treatment |
12,990 | 16,732,040 | 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 .
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 | 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 .
The present statement focuses on type 2 diabetes . | BACKGROUND Recommending increased physical activity facilitates long-term weight loss , but the optimal level of physical activity to recommend is unknown . OBJECTIVE The objective of the study was to evaluate the efficacy for long-term weight loss of recommendations for much higher physical activity than those normally used in behavioral treatments . DESIGN Overweight men and women ( n = 202 ) were r and omly assigned to either a st and ard behavior therapy ( SBT ) for obesity , incorporating an energy expenditure ( EE ) goal of 1000 kcal/wk , or to a high physical activity ( HPA ) treatment , in which the goal was an EE of 2500 kcal/wk . To help HPA treatment group participants achieve this high exercise goal , their treatment included encouragement to recruit 1 - 3 exercise partners into the study , personal counseling from an exercise coach , and small monetary incentives . RESULTS The HPA treatment group reported achieving higher mean ( + /- SD ) physical activity levels than did the SBT group at 6 mo ( EE of 2399 + /- 1571 kcal/wk compared with 1837 + /- 1431 kcal/wk ) , 12 mo ( EE of 2249 + /- 1751 kcal/wk compared with 1565 + /- 1309 kcal/wk ) , and 18 mo ( EE of 2317 + /- 1854 kcal/wk compared with 1629 + /- 1483 kcal/wk ) ( all P < 0.01 ) . Mean ( + /- SEM ) cumulative weight losses at 6 , 12 , and 18 mo in the HPA treatment group were 9.0 + /- 7.1 , 8.5 + /- 7.9 , and 6.7 + /- 8.1 kg , respectively . In the SBT group , the corresponding weight losses were 8.1 + /- 7.4 , 6.1 + /- 8.8 , and 4.1 + /- 7.3 kg , respectively . Between-group differences in weight loss were significant at 12 and 18 mo . CONCLUSION These results suggest that recommendations of higher levels of physical activity ( EE of 2500 kcal/wk ) promote long-term weight loss better than do conventional recommendations The National Weight Control Registry ( NWCR ) is , to the best of our knowledge , the largest study of individuals successful at long-term maintenance of weight loss . Despite extensive histories of overweight , the 629 women and 155 men in the registry lost an average of 30 kg and maintained a required minimum weight loss of 13.6 kg for 5 y. A little over one-half of the sample lost weight through formal programs ; the remainder lost weight on their own . Both groups reported having used both diet and exercise to lose weight and nearly 77 % of the sample reported that a triggering event had preceded their successful weight loss . Mean ( + /-SD ) current consumption reported by registry members was 5778 + /- 2200 kJ/d , with 24 + /- 9 % of energy from fat , Members also appear to be highly active : they reported expending approximately 11830 kJ/wk through physical activity . Surprisingly , 42 % of the sample reported that maintaining their weight loss was less difficult than losing weight . Nearly all registry members indicated that weight loss led to improvements in their level of energy , physical mobility , general mood , self-confidence , and physical health . In summary , the NWCR identified a large sample of individuals who were highly successful at maintaining weight loss . Future prospect i ve studies will determine variables that predict continued maintenance of weight loss Exercise is frequently identified as a predictor of weight maintenance after elective weight loss in retrospective studies of treatments for obesity . We conducted a prospect i ve study to test whether physical activity measured soon after weight loss predicted weight maintenance and to determine how much physical activity was required to optimize maintenance . Thirty-two women [ mean ( + /- SD ) age , 38 + /- 7 y ; body mass index ( in kg/m2 ) , 24 + /- 3 ] were recruited through local advertising within 3 mo of reaching their target for weight loss ( 23 + /- 9 kg ) . Total energy expenditure ( TEE ) was measured by the doubly labeled water method . Postabsorptive resting metabolic rate ( RMR ) and postpr and ial RMR [ expressed as thermic effect of a meal ( TEM ) ] were measured by respiratory gas exchange . Women in the physically active group ( ratio of TEE to RMR = 1.89 + /- 0.08 ) gained 2.5 + /- 3.1 kg during the 12 mo after reaching their target for weight loss , moderately active women ( TEE : RMR = 1.64 + /- 0.05 ) gained 9.9 + /- 10.5 kg , and sedentary women ( TEE : RMR = 1.44 + /- 0.08 ) gained 7.0 + /- 5.9 kg ( P < 0.01 ) . Retrospective analyses of weight regain as a function of energy expended in physical activity indicated a threshold for weight maintenance of 47 kJ x kg body wt(-1 ) x d(-1 ) . This corresponds to an average of 80 min/d of moderate activity or 35 min/d of vigorous activity added to a sedentary lifestyle A definitive model for predicting absolute risk of coronary heart disease ( CHD ) in male and female people with Type II diabetes is not yet available . This paper provides an equation for estimating the risk of new CHD events in people with Type II diabetes , based on data from 4540 U.K. Prospect i ve Diabetes Study male and female patients . Unlike previously published risk equations , the model is diabetes-specific and incorporates glycaemia , systolic blood pressure and lipid levels as risk factors , in addition to age , sex , ethnic group , smoking status and time since diagnosis of diabetes . All variables included in the final model were statistically significant ( P<0.001 , except smoking for which P=0.0013 ) in likelihood ratio testing . This model provides the estimates of CHD risk required by current guidelines for the primary prevention of CHD in Type II diabetes In 1997 , the World Health Organization published a l and mark document recognizing obesity as a worldwide disease that poses a serious threat to public health ( 1 ) . Persons who are overweight or obese have substantially increased risk for morbidity from numerous chronic disorders , such as diabetes ( 2 , 3 ) , hypertension ( 4 , 5 ) , and cardiovascular disease ( 6 , 7 ) . Obesity-related health risk is greater when excess fat is deposited in the abdomen region because this phenotype is a stronger predictor of cardiovascular disease and type 2 diabetes mellitus than general obesity is ( 8 - 11 ) . This may be partially explained by excess accumulation of visceral fat , an independent correlate of insulin resistance ( 9 - 11 ) and dyslipidemia ( 8 , 9 ) . These observations highlight the need to identify appropriate treatment strategies to prevent and reduce obesity and suggest that the effectiveness of these treatments would be enhanced if abdominal obesity , particularly visceral fat , was substantially reduced . Diet restriction remains the most common method of obesity reduction ( 12 ) . Despite the observation that low levels of physical activity are a major cause of obesity ( 13 ) , increased physical activity alone is not thought to be a useful strategy for obesity reduction . Some reports have suggested that physical activity in obese adults results in only modest weight loss ( approximately 1 to 2 kg ) independent of the effects of diet restriction ( 14 ) . However , these conclusions are drawn from studies in which individual energy intake and expenditure were not rigorously controlled or accurately measured ( 15 - 17 ) . Moreover , in most studies , the negative energy balance induced by exercise was modest enough that substantial weight loss was not expected ( 15 - 17 ) . Currently , no compelling evidence supports the observation that exercise alone is not a useful method for reducing total or abdominal obesity . It is well known that a single exercise session is associated with a significant improvement in insulin-stimulated glucose uptake ( 18 , 19 ) . It is also clear that weight loss is associated with an improvement in insulin action ( 20 - 24 ) . It is unclear , however , whether regular exercise improves glucose metabolism after the short-term effects of exercise and changes in body fat distribution are considered . Segal and colleagues ( 25 ) controlled for the confounding effect of the last exercise session and body composition changes and found that exercise had no independent effect on insulin sensitivity ( 25 ) . Given the established importance of insulin resistance as an antecedent to both cardiovascular disease and type 2 diabetes mellitus ( 26 ) , it is important to clarify whether exercise improves insulin action independent of fat loss . We performed a r and omized , controlled trial to determine the independent effect of diet-induced or exercise-induced weight loss on obesity and insulin resistance in moderately obese men . We also evaluated whether exercise without weight loss was associated with reductions in abdominal obesity and insulin resistance . Methods Participants Participants were recruited from Kingston , Ontario , Canada , a typical suburban region , through the general media . We selected men with a body mass index greater than 27 kg/m2 and a waist circumference greater than 100 cm whose weight had been stable ( 2 kg ) for 6 months before study entry . Participants were nonsmokers who consumed an average of fewer than two alcoholic beverages per day , had a sedentary lifestyle , and took no medications known to affect the principal outcome measures . All participants had a preparticipation medical examination that included screening for normal glucose tolerance and plasma lipid profile . A computer program was used to r and omly assign eligible men to one of the following four groups : control , diet-induced weight loss , exercise-induced weight loss , and exercise without weight loss ( Figure 1 ) . Of the 101 participants who were r and omly assigned to groups , 34 chose not to participate because they were dissatisfied with their assigned group , 5 were diabetic or dyslipidemic , and 3 were relocated because of job transfers . Those who chose not to participate and those who completed the trial were similar with regard to anthropometric variables . In addition , those who completed the trial were similar to those who did not in each group ( P > 0.10 ) . Baseline characteristics among groups were similar for all participants ( Table 1 ) . All participants gave fully informed written consent . The study was conducted in accordance with the ethical guidelines of Queen 's University . The participants did not receive monetary compensation . Figure 1 . Flow of participants through the study . Table 1 . Selected Anthropometric , Magnetic Resonance Imaging , and Metabolic Variables before Treatment and 3 Months after Treatment Diet and Exercise Regimen During the baseline period , daily energy requirements for all participants were determined by estimating resting energy expenditure and multiplying the obtained value by a factor of 1.5 ( 27 ) . All participants followed a weight maintenance diet ( 55 % to 60 % carbohydrate , 15 % to 20 % protein , and 20 % to 25 % fat ) for a 4- to 5-week baseline period . During this period , body weight was monitored to determine the accuracy of the prescribed energy requirement , which was adjusted accordingly to maintain body weight . Controls were asked to maintain body weight throughout the 12-week treatment period . Participants in the diet-induced weight loss group were asked to reduce the isocaloric diet by 700 kcal/d during the treatment period to achieve a weekly weight loss of approximately 0.6 kg . To lose the same amount of weight , participants in the exercise-induced weight loss group were asked to maintain the isocaloric diet for the duration of the treatment period and to perform exercise that expended 700 kcal/d . Participants assigned to exercise without weight loss were asked to maintain body weight . Therefore , they consumed enough calories to compensate for the energy expended during the daily exercise sessions ( approximately 700 kcal ) . At the end of the treatment period , isocaloric requirements were determined and prescribed for a 2-week weight stabilization period . All participants were free-living and consumed self-selected foods . No vitamins or other nutritional supplements were prescribed . Each person participated in a series of weekly 1-hour seminars in which a dietitian taught proper food selection and preparation . Participants were told that the composition of the maintenance and energy-reduced diets should be approximately 55 % to 60 % carbohydrate , 15 % to 20 % protein , and 20 % to 25 % fat . Participants kept and analyzed daily , detailed food records for the duration of the study period ( approximately 20 weeks ) ; the study dietitian also review ed these records . For the 2-week period during which doubly labeled water measurements were acquired ( weeks 6 and 7 ) , the diet records were analyzed by using a computerized program ( Food Processor , Esha Research , Salem , Oregon ) . Participants in both exercise groups performed daily exercise ( brisk walking or light jogging ) on a motorized treadmill for the duration of the 12-week trial . The length of each exercise session was determined by the time required to expend 700 kcal . Participants were asked to exercise at an intensity not greater than 70 % of their peak oxygen uptake ( Vo 2 ) ( approximately 80 % of maximal heart rate ) . Energy expenditure was determined by using the heart rate and oxygen consumption data that were obtained from the pretreatment grade d exercise test and were adjusted according to the results of two subsequent tests performed at weeks 4 and 8 . During each session , heart rate was monitored every 5 minutes by using an automated heart rate monitor ( Polar Oy , Kempele , Finl and ) . All exercise sessions were by appointment and were supervised . Peak Vo 2 was determined by using a grade d treadmill test and st and ard open-circuit spirometry techniques ( SensorMedics , Yorba Linda , California ) . Energy Expenditure Total energy expenditure for 14 days was measured by using a two-point doubly labeled water method ( 28 ) . Deuterium enrichment was analyzed by using a 903 deuterium dual-inlet isotope ratio mass spectrometer ( VG Isogas , Cheshire , United Kingdom ) . Oxygen-18 was determined by using a SIRA 12 isotope ratio mass spectrometer ( VG Isogas ) . Total energy expenditure was calculated by using the DeWeir formula ( 29 ) . After an overnight stay in the hospital , resting metabolic rate was measured at 7:00 a.m. by using indirect calorimetry with a modified mask system ( Teem 100 , Aerosport , Inc. , Ann Arbor , Michigan ) . Values were obtained for 30 minutes , and the last 25 minutes were used to determine resting metabolic rate . Resting systolic and diastolic blood pressure were measured when the participant was supine . Magnetic Resonance Imaging and Anthropometric Measurements Whole-body data from magnetic resonance imaging ( approximately 45 equidistant images ) were obtained with a General Electric 1.5-Tesla magnet ( Milwaukee , Wisconsin ) by using an established protocol described in detail elsewhere ( 30 ) . Once acquired , the data were transferred to a st and -alone work station ( Silicon Graphics , Mountain View , California ) for analysis with specially design ed computer software ( Tomovision , Inc. , Montreal , Canada ) , the procedures for which are described elsewhere ( 31 ) . For adipose tissue ( fat ) and skeletal muscle , volume units ( L ) were converted to mass units ( kg ) by multiplying the volumes by the assumed constant density for fat ( 0.92 kg/L ) and fat-free skeletal muscle ( 1.04 kg/L ) ( 32 ) . All anthropometric circumference measurements were obtained by using st and ard procedures described elsewhere ( 30 ) . Insulin Sensitivity and Glucose Tolerance Participants consumed a weight-maintenance diet consisting of at least 200 g of carbohydrate for a minimum of 4 days and were asked to avoid strenuous physical activity for 3 days before insulin 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 OBJECTIVE To determine the efficacy of high-intensity progressive resistance training ( PRT ) on glycemic control in older adults with type 2 diabetes . RESEARCH DESIGN AND METHODS We performed a 16-week r and omized controlled trial in 62 Latino older adults ( 40 women and 22 men ; mean + /- SE age 66 + /- 8 years ) with type 2 diabetes r and omly assigned to supervised PRT or a control group . Glycemic control , metabolic syndrome abnormalities , body composition , and muscle glycogen stores were determined before and after the intervention . RESULTS Sixteen weeks of PRT ( three times per week ) result ed in reduced plasma glycosylated hemoglobin levels ( from 8.7 + /- 0.3 to 7.6 + /- 0.2 % ) , increased muscle glycogen stores ( from 60.3 + /- 3.9 to 79.1 + /- 5.0 mmol glucose/kg muscle ) , and reduced the dose of prescribed diabetes medication in 72 % of exercisers compared with the control group , P = 0.004 - 0.05 . Control subjects showed no change in glycosylated hemoglobin , a reduction in muscle glycogen ( from 61.4 + /- 7.7 to 47.2 + /- 6.7 mmol glucose/kg muscle ) , and a 42 % increase in diabetes medications . PRT subjects versus control subjects also increased lean mass ( + 1.2 + /- 0.2 vs. -0.1 + /- 0.1 kg ) , reduced systolic blood pressure ( -9.7 + /- 1.6 vs. + 7.7 + /- 1.9 mmHg ) , and decreased trunk fat mass ( -0.7 + /- 0.1 vs. + 0.8 + /- 0.1 kg ; P = 0.01 - 0.05 ) . CONCLUSIONS PRT as an adjunct to st and ard of care is feasible and effective in improving glycemic control and some of the abnormalities associated with the metabolic syndrome among high-risk older adults with type 2 diabetes OBJECTIVE To assess the prevalence and clinical predictors of silent myocardial ischemia in asymptomatic patients with type 2 diabetes and to test the effectiveness of current American Diabetes Association screening guidelines . RESEARCH DESIGN AND METHODS In the Detection of Ischemia in Asymptomatic Diabetics ( DIAD ) study , 1,123 patients with type 2 diabetes , aged 50 - 75 years , with no known or suspected coronary artery disease , were r and omly assigned to either stress testing and 5-year clinical follow-up or to follow-up only . The prevalence of ischemia in 522 patients r and omized to stress testing was assessed by adenosine technetium-99 m sestamibi single-photon emission-computed tomography myocardial perfusion imaging . RESULTS A total of 113 patients ( 22 % ) had silent ischemia , including 83 with regional myocardial perfusion abnormalities and 30 with normal perfusion but other abnormalities ( i.e. , adenosine-induced ST-segment depression , ventricular dilation , or rest ventricular dysfunction ) . Moderate or large perfusion defects were present in 33 patients . The strongest predictors for abnormal tests were abnormal Valsalva ( odds ratio [ OR ] 5.6 ) , male sex ( 2.5 ) , and diabetes duration ( 5.2 ) . Other traditional cardiac risk factors or inflammatory and prothrombotic markers were not predictive . Ischemic adenosine-induced ST-segment depression with normal perfusion ( n = 21 ) was associated with women ( OR 3.4 ) . Selecting only patients who met American Diabetes Association guidelines would have failed to identify 41 % of patients with silent ischemia . CONCLUSIONS Silent myocardial ischemia occurs in greater than one in five asymptomatic patients with type 2 diabetes . Traditional and emerging cardiac risk factors were not associated with abnormal stress tests , although cardiac autonomic dysfunction was a strong predictor of ischemia OBJECTIVE To examine the effect of high-intensity progressive resistance training combined with moderate weight loss on glycemic control and body composition in older patients with type 2 diabetes . RESEARCH DESIGN AND METHODS Sedentary , overweight men and women with type 2 diabetes , aged 60 - 80 years ( n = 36 ) , were r and omized to high-intensity progressive resistance training plus moderate weight loss ( RT & WL group ) or moderate weight loss plus a control program ( WL group ) . Clinical and laboratory measurements were assessed at 0 , 3 , and 6 months . RESULTS HbA(1c ) fell significantly more in RT & WL than WL at 3 months ( 0.6 + /- 0.7 vs. 0.07 + /- 0.8 % , P < 0.05 ) and 6 months ( 1.2 + /- 1.0 vs. 0.4 + /- 0.8 % , P < 0.05 ) . Similar reductions in body weight ( RT & WL 2.5 + /- 2.9 vs. WL 3.1 + /- 2.1 kg ) and fat mass ( RT & WL 2.4 + /- 2.7 vs. WL 2.7 + /- 2.5 kg ) were observed after 6 months . In contrast , lean body mass ( LBM ) increased in the RT & WL group ( 0.5 + /- 1.1 kg ) and decreased in the WL group ( 0.4 + /- 1.0 ) after 6 months ( P < 0.05 ) . There were no between-group differences for fasting glucose , insulin , serum lipids and lipoproteins , or resting blood pressure . CONCLUSIONS High-intensity progressive resistance training , in combination with moderate weight loss , was effective in improving glycemic control in older patients with type 2 diabetes . Additional benefits of improved muscular strength and LBM identify high-intensity resistance training as a feasible and effective component in the management program for older patients with type 2 diabetes OBJECTIVE The purpose of this study was to evaluate whether a combined resistance and aerobic training program would improve insulin sensitivity compared with aerobic training alone in postmenopausal women with type 2 diabetes . A second objective was to relate the improved insulin sensitivity to changes in abdominal adipose tissue ( AT ) and thigh muscle density . RESEARCH DESIGN AND METHODS A total of 28 obese postmenopausal women with type 2 diabetes were r and omly assigned to one of three 16-week treatments : control , aerobic only training ( Ae only ) , or aerobic plus resistance training ( Ae+RT ) . Pre- and posttreatment outcome measures included glucose disposal by hyperinsulinemic-euglycemic clamp and computed tomography scans of abdominal AT and mid-thigh skeletal muscle . RESULTS Glucose infusion rates increased significantly ( P < 0.05 ) in the Ae+RT group . Both exercise groups had reduced abdominal subcutaneous and visceral AT and increased muscle density . The Ae+RT training group exhibited a significantly greater increase in muscle density than the Ae only group . Improved glucose disposal was independently associated with changes in subcutaneous AT , visceral AT , and muscle density . Muscle density retained a relationship with glucose disposal after controlling for abdominal AT . CONCLUSIONS Adding resistance training to aerobic training enhanced glucose disposal in postmenopausal women with type 2 diabetes . The improved insulin sensitivity is related to loss of abdominal subcutaneous and visceral AT and to increased muscle density 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 BACKGROUND Increased physical activity is related to reduced risk of cardiovascular disease , possibly because it leads to improvement in the lipoprotein profile . However , the amount of exercise training required for optimal benefit is unknown . In a prospect i ve , r and omized study , we investigated the effects of the amount and intensity of exercise on lipoproteins . METHODS A total of 111 sedentary , overweight men and women with mild-to-moderate dyslipidemia were r and omly assigned to participate for six months in a control group or for approximately eight months in one of three exercise groups : high-amount-high-intensity exercise , the caloric equivalent of jogging 20 mi ( 32.0 km ) per week at 65 to 80 percent of peak oxygen consumption ; low-amount-high-intensity exercise , the equivalent of jogging 12 mi ( 19.2 km ) per week at 65 to 80 percent of peak oxygen consumption ; or low-amount-moderate-intensity exercise , the equivalent of walking 12 mi per week at 40 to 55 percent of peak oxygen consumption . Subjects were encouraged to maintain their base-line body weight . The 84 subjects who complied with these guidelines served as the basis for the main analysis . Detailed lipoprotein profiling was performed by nuclear magnetic resonance spectroscopy with verification by measurement of cholesterol in lipoprotein subfractions . RESULTS There was a beneficial effect of exercise on a variety of lipid and lipoprotein variables , seen most clearly with the high amount of high-intensity exercise . The high amount of exercise result ed in greater improvements than did the lower amounts of exercise ( in 10 of 11 lipoprotein variables ) and was always superior to the control condition ( 11 of 11 variables ) . Both lower-amount exercise groups always had better responses than the control group ( 22 of 22 comparisons ) . CONCLUSIONS The highest amount of weekly exercise , with minimal weight change , had widespread beneficial effects on the lipoprotein profile . The improvements were related to the amount of activity and not to the intensity of exercise or improvement in fitness To assess the effects of 16 weeks of heavy resistance exercise training ( RE ) on insulin sensitivity and secretion in healthy older men aged 64 to 75 years ( N = 15 ) , stable-label ( [6,6,2H2]glucose ) intravenous glucose tolerance tests ( IVGTTs ) were performed before and 7 days after the last bout of exercise . Glucose disappearance rate ( Rd ) and an index of insulin sensitivity ( Si * ) were derived using the minimal model of labeled glucose disappearance , and insulin secretion parameters were derived from C-peptide and glucose concentrations measured during the IVGTT , using a minimal model of C-peptide secretion and kinetics . Each subject trained at an intensity of 70 % to 95 % maximum strength 4 d/wk for 16 weeks on Nautilus ( DeL and , FL ) weight-training equipment . In conjunction with exercise , six men received daily injections of recombinant human growth hormone ( [ rhGH ] 12.5 to 24 microg/kg/d ) and the other nine received placebo injections . GH/placebo injections were administered in a double-blind r and omized fashion . The RE program was supervised and progressive in nature , consisting of both upper- and lower-body exercises , and significantly increased muscle strength ( P < .05 ) with no additional benefit from rhGH except for a tendency toward a greater increase in fat-free mass ( FFM ) in the RE + GH group ( P = .06 ) . Peak glucose Rd increased following RE ( P < 01 ) , and there was a trend for an improved Si * ( ie , from 6.79 + /- 1.14 to 8.42 + /- 0.89 x 10(4 ) per min/[microU/mL ] , P = .06 ) . Peak glucose Rd and Si * were unchanged in the RE + GH group following treatment . First- and second-phase insulin secretion were not affected by RE or RE + GH . Glucose tolerance , quantified as the glucose disappearance constant ( Kg ) between 10 and 32 minutes of the IVGTT , was unchanged by exercise or hormone treatment . These findings support those of a recent study that used the hyperinsulinemic-euglycemic clamp technique ( Miller et al , J Appl Physiol 77:1122 - 1127 , 1994 ) , and suggest that when healthy older men engage in RE , whole-body glucose Rd and Si * are improved , and these beneficial effects are not only due to the acute effects of the last bout of exercise . Additionally , in six subjects who received GH , glucose Rd and Si * were not significantly improved following the RE program . Although this may suggest that GH can diminish improvements in glucose Rd and Si * that result from RE , further study is needed to confirm this observation We investigated the effect of an 8 week circuit training ( CT ) program , combining aerobic and resistance exercise , on indices of glycemic control , cardiorespiratory fitness , muscular strength and body composition in 16 subjects ( age 52 + /- 2 years ) with type 2 diabetes using a prospect i ve r and omised crossover protocol . Submaximal exercise heart rate and rate pressure product were significantly lower after training ( P<0.05 ) , whilst ventilatory threshold increased ( 11.8 + /- 0.7 vs 13.8 + /- 0.6 ml kg(-1)min(-1 ) , P<0.001 ) . Muscular strength also increased with training ( 403 + /- 30 to 456 + /- 31 kg , P<0.001 ) , whilst skinfolds ( 148.7 + /- 11.5 vs 141.1 + /- 10.7 mm , P<0.05 ) , % body fat ( 29.5 + /- 1.0 vs 28.7 + /- 1.1 % , P<0.05 ) and waist : hip ratio ( 99.2 + /- 1.5 vs 97.9 + /- 1.4 % , P<0.05 ) significantly decreased . Concurrently , peak oxygen uptake ( P<0.05 ) and exercise test duration ( P<0.001 ) increased following training , whilst glycated hemoglobin ( P<0.05 ) and fasting blood glucose ( P<0.05 ) decreased . CT is an effective method of training that improved functional capacity , lean body mass , strength and glycemic control in subjects with type 2 diabetes Cardiac rehabilitation programs have not consistently been shown to improve the psychological well being of their patients . In our study of 38 cardiac patients ( 29 men and 9 women ) , a variety of quality -of-life parameters were assessed before and after they completed either 12 weeks of high-intensity strength training or flexibility training added to their outpatient cardiac rehabilitation aerobic exercise program . The strength-trained patients increased their self-efficacy scores for lifting ( 29 % vs 4 % , p < 0.05 ) , push-ups ( 65 % vs. 17 % , p < 0.01 ) , climbing ( 36 % vs 0 % , p < 0.001 ) , and jogging ( 100 % vs -9 % , p < 0.001 ) , when compared with the flexibility-trained patients . The strength group also had greater improvements in Profile of Mood States dimensions : total mood disturbance ( 123 % vs 18 % , p < 0.05 ) , depression/dejection ( 73 % vs 15 % , p < 0.05 ) , and fatigue/inertia ( 42 % vs 3 % p < 0.05 ) , than did the flexibility group . The Medical Outcome Survey Short Form 36 role emotional health domain scores were significantly improved in the strength group when compared with the flexibility group ( 64 % vs 0 % , p < 0.05 ) , and the role limitation scores improved in both groups . Increases in strength were associated with enhanced self efficacy and improved mood and well-being scores ( n = 34 , r = 0.30 to 0.53 , p < 0.05 ) . High-intensity strength training added to a cardiac rehabilitation program of selected patients leads to improvements in quality -of-life parameters . These data , in conjunction with improvements in strength , strongly support the value of adding high-intensity strength training to cardiac rehabilitation programs 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 Chronic renal insufficiency , regardless of cause , generally progresses to end-stage renal disease ( 1 ) . Malnutrition and muscle wasting in chronic uremia often parallel the progression of renal failure ( 2 ) . They also contribute to excess morbidity and mortality in patients with renal disease ( 3 ) . Protein-restricted diets delay the progression of renal disease ( 4 , 5 ) and alleviate uremic symptoms ( 6 ) . Although nutritional status , as assessed by biochemical and anthropometric indicators , may be maintained during protein restriction ( 6 , 7 ) , studies have shown that deterioration of nutritional status is associated with low energy and protein intake in patients with chronic renal insufficiency ( 8) . Resistance training increases nitrogen retention ( 9 ) , protein synthesis ( 10 ) , and expression of insulin-like growth factor I in skeletal muscle ( 11 ) ; ameliorates losses of muscle mass and function ; and enhances quality of life ( 12 ) in both healthy and unwell persons . The anabolic potential of resistance training counteracts the catabolism of HIV infection ( 13 ) and myopathy secondary to corticosteroid use in cardiac transplantation ( 14 ) , the loss of lean tissue during energy restriction for obesity ( 15 ) , and the interleukin-mediated myopathy of chronic heart failure ( 16 ) . However , its utility as an adjunctive treatment off setting the catabolism of a low-protein diet in uremic patients is not known ( 17 ) . We conducted a r and omized , controlled trial to determine whether resistance training would preserve lean body mass , nutritional status , and muscle function through alterations in protein turnover ( synthesis and oxidation ) in patients with moderate chronic renal insufficiency who were consuming a low-protein diet to slow the progression of renal failure . Methods Study Design Patients older than 50 years of age with chronic renal insufficiency were r and omly assigned to a low-protein diet plus resistance training or a low-protein diet plus sham exercises ( referred to as low-protein diet alone ) . Patients were asked to follow a low-protein diet ( 0.6 g/kg of body weight per day ) for 2 to 8 weeks ( run-in period ) before r and omization . They continued the low-protein diet for an additional 12 weeks after r and omization ( intervention period ) ( Figure 1 ) . The Human Investigation Review Committee at Tufts University , Boston , Massachusetts , and collaborating hospitals approved the study , and written informed consent was obtained from all patients . Figure 1 . Flow of patients through the study . * The post office returned letters because addresses were incorrect or persons had relocated . No patients withdrew , experienced ineffective interventions , or were lost to follow-up . One patient in each group had incomplete postintervention measures because of health-related reasons . HNRCA = Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging . Study Sample Patients were recruited from the nephrology clinic at New Engl and Medical Center , Saint Elizabeth 's and Newton Wellesley Hospitals , and the Lahey Hitchcock Clinic , all in Boston , Massachusetts . Screening procedures took place at the Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging ( HNRCA ) at Tufts University . These procedures included sociodemographic and health history question naires ; physical examination ; electrocardiography ; blood hematology , chemistry , and urine analyses ; and a treadmill stress test . Eligibility criteria included serum creatinine concentrations between 133 and 442 mol/L ( 1.5 and 5.0 mg/dL ) and physician approval to follow a low-protein diet . A nephrologist confirmed renal diagnosis by review ing renal biochemistry results and clinical records . Exclusion criteria were myocardial infa rct ion ( within the past 6 months ) , any unstable chronic condition , dementia , alcoholism , dialysis or previous renal transplantation , current resistance training , recent involuntary weight change ( 2 kg ) , albumin level less than 30 g/L , proteinuria greater than 10 g/d , or abnormal stress test results at screening ( 18 ) . Reasons for early withdrawal from the study included loss of more than 25 % of initial body weight ; need for dialysis or transplantation ; development of any serious condition requiring hospitalization or precluding exercise ; and signs of malnutrition , such as a decrease in serum transferrin levels to less than 1.5 g/L or a 15 % decrease in hemoglobin or leukocyte count to below baseline levels . Diet Dietary intake of macronutrients and micronutrients and adherence to the low-protein diet were monitored twice per week during the run-in period and weekly during the intervention period by 3-day assisted dietary records ( including week and weekend days ) and regular meetings with the study dietitian , who was not blinded to group assignment . Dietary data were coded and analyzed by using Nutritionist-IV software ( N-Squared Computing , San Bruno , California ) . Patients collected one 24-hour urine specimen for every 3-day dietary record . Protein intake was also estimated by urea nitrogen levels ( 19 ) calculated from urine collection s and was used to assess adherence , which was defined as intake within 15 % of the prescribed low-protein intake ( 0.6 g/kg per day ) . Patients were counseled to reduce their habitual protein intake by eating food sources with less protein or by reducing portion sizes of higher-protein foods . Behavior modification strategies , including tips , recipes , food models , and self-monitoring tools for protein counts , were provided . These strategies were adapted from the Modification of Diet in Renal Disease Study ( 20 ) . Exercise Muscle strength was determined twice before r and omization and once after 12 weeks by measuring one repetition maximum ( 1 RM ) ( 21 ) using Keiser resistance training equipment ( Keiser Sports Health Equipment , Inc. , Fresno , California ) . One repetition maximum is the heaviest load that can be lifted once in good form through the full range of motion . Five machines ( chest and leg press , latissimus pull-down , knee extension , and knee flexion ) were used to include functionally large muscle groups . The better of the two baseline measurements of 1 RM was used in analyses and to set initial training loads for patients r and omly assigned to resistance training . All exercise sessions were performed at the HNRCA three times per week under the supervision of an exercise physiologist . Vital signs and body weight were recorded before each session . Patients who performed resistance training had monthly 1 RM testing on each machine . Workload during training was adjusted to reflect 80 % of the most recent 1 RM . In addition , patients ' workloads were progressively increased as appropriate according to the trainer 's objective perception of patients ' difficulty with workloads at each session . Patients performed three sets of eight repetitions on each machine per session , which lasted about 45 minutes ( 21 ) . Patients assigned to the low-protein diet alone performed five to eight sham exercises ( gentle movements while st and ing , sitting , and bending ) for the upper and lower body . These were design ed not to have a physiologic impact but to provide trainer contact time similar to that of the resistance training group . Study Measures All measures were taken before ( week 0 ) and 12 weeks after r and omization . Observers were blinded to study group assignment at all times , except during assessment s of postintervention muscle strength . Main Outcome Measures Total body potassium is the best single measure of body cell mass closely linked to functional status ( 22 ) , prognosis , and survival ( 23 ) . Body cell mass ( muscle and viscera ) comprises the metabolically active tissues where protein is targeted ( 24 ) . Potassium-40 represents approximately 0.0118 % of total body potassium . Loss of total body potassium occurs in patients following low-protein diets ( 25 ) and in patients with renal disease ( 26 ) , as well as in patients with many other wasting syndromes . Total body potassium was determined in the body composition laboratory at HNRCA , with a coefficient of variation of 5 % ( 24 ) . Regional body composition of the area involving the mid-thigh muscle was determined by computerized tomography of the nondominant thigh . A Siemens DR3 CT Scanner ( Somatom-Siemens , Erlangen , Germany ) was used to obtain an 8-mm scan at the midpoint between the inguinal crease and the proximal pole of the patella . Images were digitized and analyzed to the nearest 0.01 cm2 , as described elsewhere ( coefficient of variation , 0.5 % to 1.5 % ) ( 21 ) . Type I and type II muscle-fiber cross-sectional areas were determined from vastus lateralis muscle biopsies of the nondominant thigh , performed with a 5-mm Bergstrom needle ( 27 ) . Sections were stained with adenosine triphosphatase ( pH , 4.3 ) to visualize type I and type II fibers . A slide preparation was made for each biopsy specimen , and 50 to 150 fibers per patient were analyzed by light microscopy ( coefficient of variation , 3 % ) ( 11 , 27 ) . Anthropometry Body weights were measured to the nearest 0.1 kg on a Toledo Weight-Plate ( Bay State Scale & Systems , Inc. , Burlington , Massachusetts ) . Height was measured once to the nearest 0.25 cm , without shoes , by using a wall-mounted stadiometer . Body mass index was determined from body weight and height as kg/m2 . Biochemical Measures All measurements were collected in the fasting state in a blinded fashion at the nutrition evaluation laboratory at HNRCA ( coefficient of variation , 5 % to 10 % ) . Urea nitrogen and creatinine concentrations in serum and urine and levels of plasma insulin-like growth factor I were determined , as described elsewhere ( 25 , 27 ) . In addition , blood cell count ; hematocrit ; and levels of serum albumin , transferrin , and prealbumin were measured monthly to evaluate nutritional status . Glomerular Filtration Rate Glomerular filtration rate was measured as the renal clearance of 125I-iothalamate ( Glofil , Cypros Pharmaceutical Corp. , Carlsbad , California ) , with a coefficient of Summary of the Recommendations The U.S. Preventive Services Task Force ( USPSTF ) recommends against routine screening with resting electrocardiography ( ECG ) , exercise treadmill test ( ETT ) , or electron-beam computerized tomography ( EBCT ) scanning for coronary calcium for either the presence of severe coronary artery stenosis ( CAS ) or the prediction of coronary heart disease ( CHD ) events in adults at low risk for CHD events . This is a grade D recommendation . ( See Appendix Table 1 for a description of the USPSTF classification of recommendations . ) The USPSTF found at least fair evidence that ECG or ETT can detect some asymptomatic adults at increased risk for CHD events independent of conventional CHD risk factors ( see Clinical Considerations ) and that ETT can detect severe CAS in a small number of asymptomatic adults . Similar evidence for EBCT is limited . In the absence of evidence that such detection by ECG , ETT , or EBCT among adults at low risk for CHD events ultimately results in improved health outcomes , and because false-positive tests are likely to cause harm , including unnecessary invasive procedures , overtreatment , and labeling , the USPSTF concluded that the potential harms of routine screening for CHD in this population exceed the potential benefits . ( See Appendix Table 2 for a description of the USPSTF classification of levels of evidence . ) Appendix Table 1 . U.S. Preventive Services Task Force Grade s and Recommendations Appendix Table 2 . U.S. Preventive Services Task Force Strength of Overall Evidence The USPSTF found insufficient evidence to recommend for or against routine screening with ECG , ETT , or EBCT scanning for coronary calcium for either the presence of severe CAS or the prediction of CHD events in adults at increased risk for CHD events . This is a grade I recommendation . The USPSTF found inadequate evidence to determine the extent to which the added detection offered by ECG , ETT , or EBCT ( beyond that obtained by ascertainment of conventional CHD risk factors ) ( see Clinical Considerations ) would result in interventions that lead to improved CHD-related health outcomes among adults at increased risk for CHD events . Although there is limited evidence to determine the magnitude of harms from screening this population , harms from false-positive tests ( that is , unnecessary invasive procedures , overtreatment , and labeling ) are likely to occur . As a result , the USPSTF could not determine the balance between benefits and harms of screening this population for CHD . Clinical Considerations Several factors are associated with a higher risk for CHD events ( the major ones are nonfatal myocardial infa rct ion and coronary death ) , including older age , male gender , high blood pressure , smoking , abnormal lipid levels , diabetes , obesity , and sedentary lifestyle . A person 's risk for CHD events can be estimated on the basis of the presence of these factors . Calculators are available to ascertain a person 's risk for a CHD event ; for example , a calculator to estimate a person 's risk for a CHD event in the next 10 years can be accessed at hin.nhlbi.nih.gov/atpiii/calculator.asp?usertype=prof . Although the exact risk factors that constitute each of these categories ( low or increased risk ) have not been established , younger adults ( that is , men<50 years of age and women<60 years of age ) who have no other risk factors for CHD ( < 5 % to 10 % 10-year risk ) are considered to be at low risk . Older adults , or younger adults with one or more risk factors ( > 15 % to 20 % 10-year risk ) , are considered to be at increased risk . Screening with ECG , ETT , and EBCT could potentially reduce CHD events in 2 ways : either by detecting people at high risk for CHD events who could benefit from more aggressive risk factor modification or by detecting people with existing severe CAS whose life could be prolonged by coronary artery bypass grafting ( CABG ) surgery . However , the evidence is inadequate to determine the extent to which people detected through screening in either situation would benefit from either type of intervention . The consequences of false-positive tests may potentially outweigh the benefits of screening . False-positive tests are common among asymptomatic adults , especially women , and may lead to unnecessary diagnostic testing , overtreatment , and labeling . Because the sensitivity of these tests is limited , screening could also result in false-negative results . A negative test does not rule out the presence of severe CAS or a future CHD event . For people in certain occupations , such as pilots and heavy equipment operators ( for whom sudden incapacitation or sudden death may endanger the safety of others ) , considerations other than the health benefit to the individual patient may influence the decision to screen for CHD . Although some exercise programs initially screen asymptomatic participants with ETT , there is not enough evidence to determine the balance of benefits and harms of this practice . Discussion Coronary heart disease is the leading cause of death in the United States ; more than 700000 of the deaths in 2000 were due to heart disease ( 1 ) . The overall costs of CHD and stroke in 2003 are estimated to be greater than $ 350 billion ( 2 ) . Many clinicians ascertain a person 's overall risk for CHD events by screening for cardiac risk factors and incorporating that information into risk prediction equations derived from the Framingham or other cohort studies ( 3 , 4 ) . Asymptomatic adults clearly benefit from risk factor modification proportional to their degree of CHD risk ( that is , more intensive risk factor modification for people at higher risk ) ( 5 ) . Since those at high risk for CHD may already be receiving interventions to maximally reduce their risk for CHD events , screening may potentially be of greatest benefit to those presumed to be at intermediate risk for CHD who could be reclassified as being at high risk ( and thus treated more aggressively ) after additional testing . In addition to risk factor reduction , persons with symptoms of CHD who have severe CAS ( defined as either triple-vessel or left main coronary artery atherosclerotic disease with poor left ventricular function ) clearly benefit from CABG or percutaneous transluminal coronary angioplasty ( 6 - 8 ) . Among the asymptomatic population , those at higher risk for CHD events have a higher prevalence of severe CAS ; thus , the yield of screening is expected to be greater in this population . However , it is uncertain whether this increased yield increases the detection of people with severe CAS to an important degree and whether invasive revascularization procedures would benefit those who are asymptomatic as much as those who have symptoms of CAS . The USPSTF review ed the evidence as to whether supplementing the conventional CHD risk ascertainment strategy with additional screening using ECG , ETT , or EBCT , or using these 3 tests to identify people with severe CAS earlier , would lead to improved health outcomes in asymptomatic persons . The USPSTF found no r and omized , controlled trials with health outcomes that examined the extent to which ECG , ETT , or EBCT scanning for coronary calcium provided additional prognostic information beyond the currently used risk factor calculations . The Task Force further found that the 3 screening testsECG , ETT , and EBCThave poor to fair accuracy in predicting CHD events . Systematic review s have reported that the sensitivity of resting ECG abnormalities for CHD events is low ( 3 , 9 ) . The prevalence of the most common ECG abnormalities ( Q waves , left ventricular hypertrophy , bundle-branch blocks , and ST-segment depression ) ranges from 1 % to 10 % ( 3 ) . Only a few studies have examined ECG abnormalities in the black population . Although major ECG abnormalities may be more prevalent in black men than in white men , these abnormalities may not confer the same risk for CHD death in black men ( relative risk , 1.95 [ 95 % CI , 0.93 to 4.11 ] ) as in white men ( relative risk , 2.72 [ CI , 1.47 to 5.04 ] ) ( 10 ) . The sensitivity of ETT for the prediction of CHD events 3 to 12 years in the future ranges from 40 % to 62 % ; the positive predictive value ( PPV ) ranges from 6 % to 48 % . The higher sensitivity of ETT reported in older studies may not be accurate because of the possibility of spectrum bias ( 11 , 12 ) . The prevalence of an abnormal ETT ( ST-segment depression 1 mm ) reportedly ranges from 5 % to 25 % ( 3 ) . The yield of ETT in detecting severe CAS in asymptomatic middle-aged men is estimated to be 0.5 % ( 3 , 13 ) . The PPV for future CHD in recent cohort studies ( most of them conducted with asymptomatic men ) is low ( range , 6 % to 48 % ) ( 3 ) . Adding nuclear perfusion to ECG analysis may increase sensitivity somewhat ; however , the low PPV of ETT is due mainly to the low prevalence of CHD in asymptomatic persons and can not be corrected simply by improving test accuracy . For patients with symptoms of CHD , EBCT has a sensitivity of 80 % and a specificity of 40 % for detecting angiographically demonstrated CAS ( 14 ) ; similar data for those who have no symptoms are lacking . A systematic review reported that higher calcium scores on EBCT were associated with higher risk for CHD events ( 3 ) . This review concluded that EBCT may have a role in better defining risk for CHD events in those who have been identified as being at intermediate risk based on traditional risk factors , but no study has examined the effect of EBCT data on clinical decision making ( 3 ) . Potential harms of screening asymptomatic patients for CHD include unnecessary invasive testing ( for example , coronary angiography ) and labeling of those who have had false-positive test results . In low-risk asymptomatic population s , most positive ECG test results occur in those who will not have a CHD event in the next 5 to 10 years ( 3 ) . One study reported that 71 % of those without symptoms who had an abnormal ETT had no angiographically demonstrable CAS ( 15 ) . While the yield of screening is low in those at low risk for CHD , the potential for This study assessed the effects of short-term circuit weight training ( CWT ) on glycaemic control in NIDDM . Twenty-seven untrained , sedentary subjects ( mean age , 51 ) with NIDDM participated in an 8-week r and omised , controlled study , involving either CWT 3 days/week ( n = 15 ) or no formal exercise ( control ) ( n = 12 ) . All subjects performed regular self-blood glucose monitoring throughout . Fasting serum glucose and insulin were measured following a 12-h fast and during an oral glucose tolerance test ( 75 g ) before and after 8 weeks . Twenty-one subjects completed the study ( CWT , n = 11 ) ( Control , n = 10 ) . Strength for all exercises improved significantly after CWT . Pooled time-series analysis , using a r and om effects model , revealed an overall decrease in self-monitored glucose levels with CWT compared to controls . Significant reductions from baseline values were observed in both the glucose ( -213 mmol l-1 per 120 min , P < 0.05 ) and insulin ( -6130 pmol l-1 per 120 min , P < 0.05 ) area under the curve following CWT relative to controls . After adjustment for body mass changes , the change in self-monitored glucose levels and insulin area under the curve , but not glucose area under the curve , remained significant . Short-term CWT therefore may provide a practical exercise alternative in the lifestyle management of this condition OBJECTIVE To examine whether improvements in glycemic control and body composition result ing from 6 months of supervised high-intensity progressive resistance training could be maintained after an additional 6 months of home-based resistance training . RESEARCH DESIGN AND METHODS We performed a 12-month r and omized controlled trial in 36 sedentary , overweight men and women with type 2 diabetes ( aged 60 - 80 years ) who were r and omly assigned to moderate weight loss plus high-intensity progressive resistance training ( RT&WL group ) or moderate weight loss plus a control program ( WL group ) . Supervised gymnasium-based training for 6 months was followed by an additional 6 months of home-based training . Glycemic control ( HbA1c ) , body composition , muscle strength , and metabolic syndrome abnormalities were assessed at 0 , 3 , 6 , 9 , and 12 months . RESULTS Compared with the WL group , HbA1c decreased significantly more in the RT&WL group ( -0.8 % ) during 6 months of supervised gymnasium-based training ; however , this effect was not maintained after an additional 6 months of home-based training . In contrast , the greater increase in lean body mass ( LBM ) observed in the RT&WL group compared with the WL group ( 0.9 kg , P < 0.05 ) after the gymnasium-based training tended to be maintained after the home-based training ( 0.8 kg , P = 0.08 ) . Similarly , the gymnasium-based increases in upper body and lower body muscle strength in the RT&WL group were maintained over the 12 months ( P < 0.001 ) . There were no between-group differences for changes in body weight , fat mass , fasting glucose , or insulin at 6 or 12 months . CONCLUSIONS In older adults with type 2 diabetes , home-based progressive resistance training was effective for maintaining the gymnasium-based improvements in muscle strength and LBM but not glycemic control . Reductions in adherence and exercise training volume and intensity seem to impede the effectiveness of home-based training for maintaining improved glycemic control The purpose of this study was to determine the effects of aerobic training on indices of glycemic control , blood pressure , serum lipids , and diabetic nephropathy ( DN ) in an animal model of insulin deficient diabetes mellitus . Thirty-four male Sprague-Dawley rats made diabetic with streptozocin were r and omly assigned to a trained group or a sedentary group . Fifteen sedentary-nondiabetic rats served as a control group . The animals were trained on a treadmill at 18 m.min-1 , 8 degrees incline for 120 min.d-1 , 5 d.wk-1 . Blood and 24 h urine collection s were obtained at various intervals throughout the study . At 21 wk of age systolic blood pressure was measured and kidney tissue was obtained for light and electron microscopy . Analysis of variance was used to detect differences among the groups ( P < or = 0.05 ) . The diabetes produced in this investigation result ed in hyperglycemia , increased urine albumin and total protein excretion , elevated systolic blood pressure , increased fractional volume of the mesangium , and widening of the glomerular basement membrane in the sedentary-diabetic animals . Aerobic training significantly reduced the increase in fractional volume of the mesangium and fructosamine . Most importantly , aerobic training did not augment the renal damage seen in DN A r and omized controlled study of 19 patients with diabetes mellitus ( 10 men , 9 women ) was undertaken to determine the effects of home exercise therapy on joint mobility and plantar pressures . Of the 19 subjects , 9 subjects performed unsupervised active and passive range-of-motion exercises of the joints in their feet . Each subject was evaluated for joint stiffness and peak plantar pressures at the beginning and conclusion of the study . After only 1 month of therapy , a statistically significant average decrease of 4.2 % in peak plantar pressures was noted in the subjects performing the range-of-motion exercises . In the control group , an average increase of 4.4 % in peak plantar pressures was noted . Although the joint mobility data revealed no statistically significant differences between the groups , there was a trend for a decrease in joint stiffness in the treatment group . The results of this study demonstrate that an unsupervised range-of-motion exercise program can reduce peak plantar pressures in the diabetic foot . Given that high plantar pressures have been linked to diabetic neuropathic ulceration , it may be possible to reduce the risk of such ulceration with this therapy Exercise has become a st and ard therapy for patients with type 2 diabetes ( 1 ) . Regular exercise improves conventional clinical risk factors , cardiorespiratory fitness , and components of the insulin resistance syndrome ( 2 - 6 ) . However , it is unclear whether physical activity improves the prognosis of patients with diabetes . No data are available on the association of physical activity or cardiorespiratory fitness with mortality in patients with diabetes . The overall benefit of exercise for these patients is unclear , and some experts are concerned that macrovascular and microvascular complications may be worsened by an exercise program ( 1 , 7 ) . Some consider exercise only as a supplement to diet therapy ( 8) . Studies have shown repeatedly that low cardiorespiratory fitness and physical inactivity are directly associated with cardiovascular disease and all-cause mortality ( 9 - 14 ) , and our preliminary study with a small number of end points suggested that this association might persist across plasma glucose levels ( 15 ) . In the current study , we evaluated the prospect i ve association of cardiorespiratory fitness and physical inactivity with mortality in men who have type 2 diabetes . Methods The material presented in this report was derived from the Aerobics Center Longitudinal Study ( ACLS ) , a prospect i ve observational study of patients examined at The Cooper Clinic in Dallas , Texas . The study was review ed and approved annually by the institutional review board at The Cooper Institute . Additional details of study methods and study group characteristics of this cohort have been published elsewhere ( 12 , 13 ) . Patients Participants were men with type 2 diabetes who completed a baseline medical evaluation at The Cooper Clinic in Dallas , Texas , during 1970 to 1993 . These men came to The Cooper Clinic for a medical examination and health counseling . Many were sent by their employers for these services , some were referred by their personal physicians , and others were self-referred . More than 92 % of the patients are white , and most are employed in executive or professional occupations ; more than 75 % are college graduates . Study participants come from middle and upper socioeconomic strata , but they are similar to other well-characterized study group-based cohorts in terms of blood pressure , cholesterol level , body weight , and cardiorespiratory fitness ( 6 , 16 , 17 ) . We excluded men taking insulin and those with a history of cancer at baseline . Clinical Examination The baseline evaluation was performed after participants gave informed written consent for the baseline medical examination and registration in the follow-up study . Examinations followed an overnight fast of at least 12 hours and included personal and family health histories , a question naire on demographic characteristics and health habits , a physical examination , a maximal exercise test on a treadmill , anthropometry , electrocardiography , blood chemistry analyses , and blood pressure measurement . Technicians who followed a st and ard manual of operations administered all procedures . Question naire Patients completed an extensive self-report of personal and family medical diseases and conditions . Each clinic physician examines only four or five patients per day and thus has time for thorough additional probing of items on the self-reported question naire . This complete review of the patient 's medical history and the subsequent physical examination are strengths of the ACLS and provide a more thorough evaluation of baseline health status than is possible in many epidemiologic studies . The question naire also featured items on health habits , including current smoking status and smoking history and whether the participant was currently dieting to lose weight or following any other special dietary plan . Physical activity pattern was ascertained by self-report on the question naire . An extensive list of leisure-time physical activities was presented , and participants indicated activities in which they had participated in the 3 months before the examination . In later study years , they gave additional details on the number of times per week and the duration of exercise sessions . Laboratory Evaluations Cardiorespiratory fitness was assessed by using a maximal exercise test that followed a modified version of Balke and Ware 's protocol ( 18 ) . Briefly , the test began with the participant walking on a horizontal treadmill at 88 m/min . After the first minute , the elevation increased to 2 % , and it further increased 1 % each minute up to 25 minutes . For the few patients who were still able to continue , the elevation was held constant after 25 minutes and the speed increased to 5.4 m/min until the participant reached volitional fatigue . Exercise test performance with this protocol correlates highly with measured maximal oxygen uptake ( r=0.92 ) ( 19 ) . Serum sample s were analyzed by using automated techniques in a laboratory that participates in and meets the quality control st and ards of the Centers for Disease Control and Prevention Lipid St and ardization Program . Blood pressure was measured by auscultatory methods with a mercury sphygmomanometer according to American Heart Association guidelines ( 20 ) . The lowest of three blood pressure measurements at the clinic examination was recorded as the baseline blood pressure . Height and weight were measured by using a st and ard beam-balance scale and stadiometer , and body mass index was calculated . Type 2 Diabetes Diabetes was defined according to criteria of the American Diabetes Association : fasting plasma glucose level of 7.0 mmol/L or greater ( 126 mg/dL ) ( 21 ) . Three hundred seventy patients who did not meet this criterion but who gave a history of physician-diagnosed diabetes were considered to have diabetes . Patients were classified as having known diabetes or unknown diabetes according to their diabetes status before the baseline Cooper Clinic examination . Definition of Exposure Variables The principal exposure variables used in our analyses were cardiorespiratory fitness and self-reported physical activity . These exposures were determined at the baseline examination . Cardiorespiratory Fitness We categorized total time from the maximal exercise test into frequency distributions for specific age groups ( 30 to 39 , 40 to 49 , 50 to 59 , and 60 years ) . The least fit 20 % of the participants in each age group were classified as low fit , the next 40 % of the distribution as moderately fit , and the highest 40 % as high fit . We have used these cut-points to define fitness in previous studies ( 12 , 13 ) , and they are based on our entire cohort rather than on diabetic patients only . We selected these cut-points before undertaking the current analysis . Cardiorespiratory fitness is expressed as maximal metabolic units ( METs ) attained during the exercise test . The METs are calculated as the working metabolic rate divided by the resting metabolic rate , and 1 MET is equivalent to an oxygen uptake of 3.5 mL1 kg 1 . Physical Activity Patients who reported walking , jogging , or participating in aerobic exercise programs in the 3 months before the examination were classified as active , regardless of the frequency and duration of exercise . Otherwise , patients were classified as inactive . In our cohort , more than 76 % of men who reported being active at baseline still reported being active at the second visit after more than 1 year . In comparison , only 34 % of men who reported being inactive at baseline reported being active at the second examination ( P<0.001 ) . Self-reported physical activity status in our cohort is correlated with maximal exercise test performance ( 6 , 22 ) . Baseline or Parental Cardiovascular Disease We defined baseline cardiovascular disease as a personal history of heart attack , stroke , or a revascularization procedure ; an abnormal resting or exercise electrocardiogram ; or the highest heart rate during exercise testing that was less than 85 % of the age-predicted maximal heart rate ( [ 220 age in years ] 0.85 ) . Men who reported a history of cardiovascular disease in either parent were classified as having parental cardiovascular disease . Conventional Cardiovascular Disease Risk Factors We assigned men to risk strata for conventional cardiovascular disease risk factors on the basis of recent recommendations ( 23 ) . We defined high blood pressure as systolic blood pressure of 140 mm Hg or more , diastolic blood pressure of 90 mm Hg or more , or a history of physician-diagnosed hypertension . We classified participants with a total cholesterol level of 6.2 mmol/L ( 240 mg/dL ) or more as having high cholesterol , those with self-reported current smoking as current smokers , those with a self-reported parental history of myocardial infa rct ion or stroke as having a history of parental cardiovascular disease , those with a body mass index less than 25.0 kg/m2 as normal weight , and those with a body mass index of 25.0 kg/m2 or more as overweight . Statistical Analysis Our primary outcome measure was all-cause mortality . We used the National Death Index to identify decedents in the ACLS . The National Death Index has been shown to be an effective , accurate means of ascertaining deaths in the general population , with a sensitivity of about 96 % and a specificity of 100 % ( 24 ) . We obtained official death certificates from states in which there were ACLS decedents , and we had the certificates coded by a nosologist according to the International Classification of Diseases , Ninth Revision . Only the underlying cause of death was used in analyses for this report . Data were analyzed by using the SAS statistical package ( SAS Institute , Inc. , Cary , North Carolina ) . The analyses assumed that physical activity and fitness were essentially unchanged during the study period . We used survival curves to estimate survival function against time and log [ log ( survival time ) ] to check the proportional hazards model assumption . Log [ log ( survival function ) ] estimates were approximately parallel across exposure Cardiovascular disease is the leading cause of death in persons with diabetes mellitus . This disorder affects approximately 16 million Americans , at least 15 million of whom have type 2 diabetes mellitus ( 1 ) . Among diabetic persons , coronary heart disease causes more than 50 % of all deaths and stroke causes an additional 15 % ( 2 ) . Diabetic women are at particularly high risk for cardiovascular disease , and diabetes eliminates the usual female advantage for death from coronary disease . While an inverse association between increased physical activity and lower risk for cardiovascular disease is well established in the general population ( 3 ) , sparse data are available among diabetic persons ( 4 , 5 ) . Intervention studies have shown that exercise increases insulin sensitivity and glucose tolerance and induces favorable changes in blood lipid levels among persons with type 2 diabetes mellitus ( 6 ) . Exercise as an adjunct to diet regimens yields greater and more sustained weight loss in obese patients with type 2 diabetes mellitus ( 7 ) . Even moderately intense exercise , such as walking , improves insulin sensitivity and reduces body weight ( 8) . Because walking is safe and easy , it may provide a promising way to reduce risk for cardiovascular events among diabetic persons . In this study , we examined in detail the relationship between levels of physical activity and incidence of coronary heart disease and stroke among women with type 2 diabetes mellitus in the Nurses ' Health Study . In particular , we evaluated walking ( the most common form of physical activity among diabetic persons ) in relation to cardiovascular events . Methods Study Sample The Nurses ' Health Study cohort was established in 1976 . The original cohort consisted of 121 700 female registered nurses who were 30 to 55 years of age and resided in 11 large U.S. states . The nurses completed a mailed question naire about their medical history and lifestyle , and follow-up question naires administered every 2 years up date information on potential risk factors and identify newly diagnosed cases of coronary heart disease and other illness . Our study includes 5125 women who , on any question naire from 1976 to 1992 , reported having physician-diagnosed diabetes mellitus and being 30 years of age or older at disease onset ( a working definition for type 2 diabetes mellitus ) . Women who reported a history of coronary heart disease ( including myocardial infa rct ion , angina , or coronary revascularization ) , stroke , or cancer on or before the 1980 question naire ( when physical activity was first assessed ) were excluded at baseline . The follow-up rate for nonfatal events was 97 % of the total potential person-years . Confirmation of Diabetes Mellitus A supplementary question naire regarding symptoms , diagnostic tests , and hypoglycemic therapy was mailed to women who indicated on any biennial question naire that they had received a diagnosis of diabetes . A case of diabetes was considered confirmed if at least one of the following was reported on the supplementary question naire : 1 ) classic symptoms plus a fasting plasma glucose level of at least 140 mg/dL ( 7.8 mmol/L ) or a r and om plasma glucose level of at least 200 mg/dL [ 11.1 mmol/L ] , 2 ) at least two elevated plasma glucose concentrations on different occasions ( a fasting level 140 mg/dL [ 7.8 mmol/L ] or a r and om level 200 mg/dL [ 11.1 mmol/L ] , a concentration 200 mg/dL after 2 hours or more on oral glucose tolerance testing , or both ] in the absence of symptoms , or 3 ) treatment with hypoglycemic medication ( insulin or an oral hypoglycemic agent ) . The validity of this question naire has been verified in a sub sample of the study cohort ( 9 ) . Of a r and om sample of 84 women classified by the question naire as having type 2 diabetes mellitus , 71 gave permission for their medical records to be review ed ; records were available for 62 of 71 . An endocrinologist blinded to the information on the supplementary question naires review ed the records according to National Diabetes Data Group ( NDDG ) criteria ( 10 ) . The diagnosis of type 2 diabetes mellitus was confirmed in 61 of 62 women ( 98 % ) ( 9 ) . A secondary set of analyses included only women with definite type 2 diabetes mellitus according to the NDDG criteria . We used the NDDG diagnostic criteria because the analytic cohort preceded the American Diabetes Association guideline , which was published in 1997 ( 11 ) . Assessment of Physical Activity Women were first asked about physical activity on the 1980 question naire . They were asked to report the average number of hours they had spent each week during the past year on such moderate and vigorous recreational activities as vigorous sports , jogging , brisk walking or striding , bicycling , heavy gardening , and heavy housework . On the 1982 question naire , women were asked a slightly different question : For how many hours per week , on average , do you engage in activity strenuous enough to build up a sweat ? In 1986 , 1988 , and 1992 , women were asked to report the average time spent per week on the following activities : walking , jogging , running , bicycling , lap swimming , playing tennis or squash , and participating in calisthenics . They were also asked to report the average number of flights of stairs that they climbed each week . Women also reported their usual walking pace : easy ( < 2 miles per hour [ mph ] ) , average ( 2 to 2.9 mph ) , brisk ( 3 to 3.9 mph ) , or very brisk ( 4 mph ) . Because fewer than 2 % of women reported a very brisk pace , we combined the brisk and very brisk categories in analyses of walking pace and diabetes risk . For 1980 , 1982 , 1986 , 1988 , and 1992 , we created a measure of average hours per week spent in moderate or vigorous recreational activities ( all activities described above except for hours spent walking at an easy or average pace ) . For 1986 , 1988 , and 1992 , using a list of physical activities ( 12 ) , we calculated a weekly metabolic equivalent of task ( MET ) score for total physical activities , vigorous activities ( requiring 6 MET/h ) , nonvigorous activities ( requiring<6 MET/h ) , and walking . The validity of the question naire in assessing physical activity has been described elsewhere ( 13 ) . Correlation between activities reported in four 1-week diaries and those reported on the question naire was 0.62 . Ascertainment of End Points The primary end points for this study were incident coronary heart disease ( defined as nonfatal myocardial infa rct ion or fatal coronary heart disease ) and stroke that occurred after the 1980 question naire was returned but before 1 June 1994 . We requested permission to review the medical records of women who reported having a nonfatal myocardial infa rct ion or stroke on a follow-up question naire . Study physicians with no knowledge of the women 's self-reported risk factors review ed the records . Nonfatal myocardial infa rct ion was confirmed if it met the criteria of the World Health Organization of symptoms and the patient 's records showed diagnostic electrocardiographic changes or elevated cardiac enzyme levels ( 14 ) . Infa rct ions that required hospital admission and were confirmed by interview or letter but for which no medical records were available were design ated as probable ( 19 % ) . We included all confirmed and probable cases in the analyses because the results were the same after probable cases were excluded . Stroke was confirmed by medical records according to the criteria of the National Survey of Stroke ( 15 ) , which define it as a constellation of neurologic deficits , sudden or rapid in onset , lasting at least 24 hours . Events were further subclassified as hemorrhagic stroke ( subarachnoid or intraparenchymal ) , ischemic stroke ( thrombotic or embolic ) , or stroke of unknown cause . Deaths were reported by next of kin and the U.S. Postal Service or were ascertained through the National Death Index . After combining all sources , we estimated that follow-up for deaths was more than 98 % complete ( 16 ) . Fatal coronary heart disease was defined as fatal myocardial infa rct ion if confirmed by hospital records or autopsy or if coronary heart disease was listed as the cause of death on the death certificate , was the underlying and most plausible cause , and was supported by evidence of previous coronary heart disease . The cause of death on the death certificate was never in itself considered to provide sufficient confirmation of death from coronary heart disease . We also included sudden death within 1 hour of onset of symptoms in women with no plausible cause other than coronary disease ( 8 % of fatal cases ) . Fatal strokes were coded by using the same criteria as nonfatal cases , but autopsy evidence as well as the death certificate listing was accepted . Statistical Analysis The study base was defined as the pool of person-time that gives rise to incident cases of cardiovascular disease among patients with both prevalent and incident diabetes . We conducted two sets of analyses , one using 1980 as the baseline to evaluate long-term overall effects of moderate or vigorous activities and the other using 1986 as the baseline to examine specific effects of regular walking . Person-time for each participant was calculated from the date of return of the 1980 or 1986 question naires to the date of confirmed cardiovascular disease , death from any cause , or 1 June 1994 , whichever came first . In the first set of analyses , relative risks were computed as the incidence rate in a specific category of average hours spent on moderate or vigorous activities per week divided by the incidence rate in the lowest category , with adjustment for 5-year categories of age . Tests of linear trend across increasing categories of average hours spent on moderate or vigorous activities were conducted by treating the categories as a single continuous variable and assigning the median score for the category as its value . To best represent long-term levels of physical activity for individual women and to reduce measurement error , we created measures of the cumulative average of physical |
12,991 | 31,632,907 | Compared with PD-L1 inhibitors , PD-1 inhibitors neither increased trAEs nor irAEs significantly .
Conclusions : Current data showed that PD-L1 inhibitors had the best safety on both trAEs and irAEs . | Background : Comprehensive evidence comparing treatment-related adverse events ( trAEs ) among PD-1/PD-L1 inhibitors is unavailable . | AIM To evaluate the protocol -specified final analysis of overall survival ( OS ) in the KEYNOTE-002 study ( NCT01704287 ) of pembrolizumab versus chemotherapy in patients with ipilimumab-refractory , advanced melanoma . METHODS In this r and omised , phase II study , eligible patients had advanced melanoma with documented progression after two or more ipilimumab doses , previous BRAF or MEK inhibitor or both , if BRAFV600 mutant-positive . Patients were r and omised to pembrolizumab 2 mg/kg or 10 mg/kg every 3 weeks or investigator-choice chemotherapy . Crossover to pembrolizumab was allowed following progression on chemotherapy . The protocol -specified final OS was performed in the intent-to-treat population . Survival was positive if p < 0.01 in one pembrolizumab arm . RESULTS A total of 180 patients were r and omised to pembrolizumab 2 mg/kg , 181 to pembrolizumab 10 mg/kg and 179 to chemotherapy . At a median follow-up of 28 months ( range 24.1 - 35.5 ) , 368 patients died and 98 ( 55 % ) crossed over to pembrolizumab . Pembrolizumab 2 mg/kg ( hazard ratio [ HR ] 0.86 , 95 % confidence interval [ CI ] 0.67 - 1.10 , p = 0.117 ) and 10 mg/kg ( 0.74 , 0.57 - 0.96 , p = 0.011 ) result ed in a non-statistically significant improvement in OS versus chemotherapy ; median OS was 13.4 ( 95 % CI 11.0 - 16.4 ) and 14.7 ( 95 % CI 11.3 - 19.5 ) , respectively , versus 11.0 months ( 95 % CI 8.9 - 13.8 ) , with limited improvement after censoring for crossover . Two-year survival rates were 36 % and 38 % , versus 30 % . Progression-free survival , objective response rate and duration of response improved with pembrolizumab versus chemotherapy , regardless of dose . Grade III-V treatment-related adverse events occurred in 24 ( 13.5 % ) , 30 ( 16.8 % ) and 45 ( 26.3 % ) patients , respectively . CONCLUSION Improvement in OS with pembrolizumab was not statistically significant at either dose versus chemotherapy BACKGROUND Limited evidence exists to show that adding a third agent to platinum-doublet chemotherapy improves efficacy in the first-line advanced non-small-cell lung cancer ( NSCLC ) setting . The anti-PD-1 antibody pembrolizumab has shown efficacy as monotherapy in patients with advanced NSCLC and has a non-overlapping toxicity profile with chemotherapy . We assessed whether the addition of pembrolizumab to platinum-doublet chemotherapy improves efficacy in patients with advanced non-squamous NSCLC . METHODS In this r and omised , open-label , phase 2 cohort of a multicohort study ( KEYNOTE-021 ) , patients were enrolled at 26 medical centres in the USA and Taiwan . Patients with chemotherapy-naive , stage IIIB or IV , non-squamous NSCLC without targetable EGFR or ALK genetic aberrations were r and omly assigned ( 1:1 ) in blocks of four stratified by PD-L1 tumour proportion score ( < 1 % vs ≥1 % ) using an interactive voice-response system to 4 cycles of pembrolizumab 200 mg plus carboplatin area under curve 5 mg/mL per min and pemetrexed 500 mg/m2 every 3 weeks followed by pembrolizumab for 24 months and indefinite pemetrexed maintenance therapy or to 4 cycles of carboplatin and pemetrexed alone followed by indefinite pemetrexed maintenance therapy . The primary endpoint was the proportion of patients who achieved an objective response , defined as the percentage of patients with radiologically confirmed complete or partial response according to Response Evaluation Criteria in Solid Tumors version 1.1 assessed by masked , independent central review , in the intention-to-treat population , defined as all patients who were allocated to study treatment . Significance threshold was p<0·025 ( one sided ) . Safety was assessed in the as-treated population , defined as all patients who received at least one dose of the assigned study treatment . This trial , which is closed for enrolment but continuing for follow-up , is registered with Clinical Trials.gov , number NCT02039674 . FINDINGS Between Nov 25 , 2014 , and Jan 25 , 2016 , 123 patients were enrolled ; 60 were r and omly assigned to the pembrolizumab plus chemotherapy group and 63 to the chemotherapy alone group . 33 ( 55 % ; 95 % CI 42 - 68 ) of 60 patients in the pembrolizumab plus chemotherapy group achieved an objective response compared with 18 ( 29 % ; 18 - 41 ) of 63 patients in the chemotherapy alone group ( estimated treatment difference 26 % [ 95 % CI 9 - 42 % ] ; p=0·0016 ) . The incidence of grade 3 or worse treatment-related adverse events was similar between groups ( 23 [ 39 % ] of 59 patients in the pembrolizumab plus chemotherapy group and 16 [ 26 % ] of 62 in the chemotherapy alone group ) . The most common grade 3 or worse treatment-related adverse events in the pembrolizumab plus chemotherapy group were anaemia ( seven [ 12 % ] of 59 ) and decreased neutrophil count ( three [ 5 % ] ) ; an additional six events each occurred in two ( 3 % ) for acute kidney injury , decreased lymphocyte count , fatigue , neutropenia , and sepsis , and thrombocytopenia . In the chemotherapy alone group , the most common grade 3 or worse events were anaemia ( nine [ 15 % ] of 62 ) and decreased neutrophil count , pancytopenia , and thrombocytopenia ( two [ 3 % ] each ) . One ( 2 % ) of 59 patients in the pembrolizumab plus chemotherapy group experienced treatment-related death because of sepsis compared with two ( 3 % ) of 62 patients in the chemotherapy group : one because of sepsis and one because of pancytopenia . INTERPRETATION Combination of pembrolizumab , carboplatin , and pemetrexed could be an effective and tolerable first-line treatment option for patients with advanced non-squamous NSCLC . This finding is being further explored in an ongoing international , r and omised , double-blind , phase 3 study . FUNDING Merck & BACKGROUND Atezolizumab is a humanised antiprogrammed death-lig and 1 ( PD-L1 ) monoclonal antibody that inhibits PD-L1 and programmed death-1 ( PD-1 ) and PD-L1 and B7 - 1 interactions , reinvigorating anticancer immunity . We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer . METHODS We did a r and omised , open-label , phase 3 trial ( OAK ) in 194 academic or community oncology centres in 31 countries . We enrolled patients who had squamous or non-squamous non-small-cell lung cancer , were 18 years or older , had measurable disease per Response Evaluation Criteria in Solid Tumors , and had an Eastern Cooperative Oncology Group performance status of 0 or 1 . Patients had received one to two previous cytotoxic chemotherapy regimens ( one or more platinum based combination therapies ) for stage IIIB or IV non-small-cell lung cancer . Patients with a history of autoimmune disease and those who had received previous treatments with docetaxel , CD137 agonists , anti-CTLA4 , or therapies targeting the PD-L1 and PD-1 pathway were excluded . Patients were r and omly assigned ( 1:1 ) to intravenously receive either atezolizumab 1200 mg or docetaxel 75 mg/m2 every 3 weeks by permuted block r and omisation ( block size of eight ) via an interactive voice or web response system . Co primary endpoints were overall survival in the intention-to-treat ( ITT ) and PD-L1-expression population TC1/2/3 or IC1/2/3 ( ≥1 % PD-L1 on tumour cells or tumour-infiltrating immune cells ) . The primary efficacy analysis was done in the first 850 of 1225 enrolled patients . This study is registered with Clinical Trials.gov , number NCT02008227 . FINDINGS Between March 11 , 2014 , and April 29 , 2015 , 1225 patients were recruited . In the primary population , 425 patients were r and omly assigned to receive atezolizumab and 425 patients were assigned to receive docetaxel . Overall survival was significantly longer with atezolizumab in the ITT and PD-L1-expression population s. In the ITT population , overall survival was improved with atezolizumab compared with docetaxel ( median overall survival was 13·8 months [ 95 % CI 11·8 - 15·7 ] vs 9·6 months [ 8·6 - 11·2 ] ; hazard ratio [ HR ] 0·73 [ 95 % CI 0·62 - 0·87 ] , p=0·0003 ) . Overall survival in the TC1/2/3 or IC1/2/3 population was improved with atezolizumab ( n=241 ) compared with docetaxel ( n=222 ; median overall survival was 15·7 months [ 95 % CI 12·6 - 18·0 ] with atezolizumab vs 10·3 months [ 8·8 - 12·0 ] with docetaxel ; HR 0·74 [ 95 % CI 0·58 - 0·93 ] ; p=0·0102 ) . Patients in the PD-L1 low or undetectable subgroup ( TC0 and IC0 ) also had improved survival with atezolizumab ( median overall survival 12·6 months vs 8·9 months ; HR 0·75 [ 95 % CI 0·59 - 0·96 ] ) . Overall survival improvement was similar in patients with squamous ( HR 0·73 [ 95 % CI 0·54 - 0·98 ] ; n=112 in the atezolizumab group and n=110 in the docetaxel group ) or non-squamous ( 0·73 [ 0·60 - 0·89 ] ; n=313 and n=315 ) histology . Fewer patients had treatment-related grade 3 or 4 adverse events with atezolizumab ( 90 [ 15 % ] of 609 patients ) versus docetaxel ( 247 [ 43 % ] of 578 patients ) . One treatment-related death from a respiratory tract infection was reported in the docetaxel group . INTERPRETATION To our knowledge , OAK is the first r and omised phase 3 study to report results of a PD-L1-targeted therapy , with atezolizumab treatment result ing in a clinical ly relevant improvement of overall survival versus docetaxel in previously treated non-small-cell lung cancer , regardless of PD-L1 expression or histology , with a favourable safety profile . FUNDING F. Hoffmann-La Roche Ltd , Genentech , Background The programmed death 1 ( PD‐1 ) inhibitor pembrolizumab has been found to prolong progression‐free and overall survival among patients with advanced melanoma . We conducted a phase 3 double‐blind trial to evaluate pembrolizumab as adjuvant therapy in patients with resected , high‐risk stage III melanoma . Methods Patients with completely resected stage III melanoma were r and omly assigned ( with stratification according to cancer stage and geographic region ) to receive 200 mg of pembrolizumab ( 514 patients ) or placebo ( 505 patients ) intravenously every 3 weeks for a total of 18 doses ( approximately 1 year ) or until disease recurrence or unacceptable toxic effects occurred . Recurrence‐free survival in the overall intention‐to‐treat population and in the subgroup of patients with cancer that was positive for the PD‐1 lig and ( PD‐L1 ) were the primary end points . Safety was also evaluated . Results At a median follow‐up of 15 months , pembrolizumab was associated with significantly longer recurrence‐free survival than placebo in the overall intention‐to‐treat population ( 1‐year rate of recurrence‐free survival , 75.4 % [ 95 % confidence interval { CI } , 71.3 to 78.9 ] vs. 61.0 % [ 95 % CI , 56.5 to 65.1 ] ; hazard ratio for recurrence or death , 0.57 ; 98.4 % CI , 0.43 to 0.74 ; P<0.001 ) and in the subgroup of 853 patients with PD‐L1–positive tumors ( 1‐year rate of recurrence‐free survival , 77.1 % [ 95 % CI , 72.7 to 80.9 ] in the pembrolizumab group and 62.6 % [ 95 % CI , 57.7 to 67.0 ] in the placebo group ; hazard ratio , 0.54 ; 95 % CI , 0.42 to 0.69 ; P<0.001 ) . Adverse events of grade s 3 to 5 that were related to the trial regimen were reported in 14.7 % of the patients in the pembrolizumab group and in 3.4 % of patients in the placebo group . There was one treatment‐related death due to myositis in the pembrolizumab group . Conclusions As adjuvant therapy for high‐risk stage III melanoma , 200 mg of pembrolizumab administered every 3 weeks for up to 1 year result ed in significantly longer recurrence‐free survival than placebo , with no new toxic effects identified . ( Funded by Merck ; Clinical Trials.gov number , NCT02362594 ; EudraCT number , 2014‐004944‐37 . BACKGROUND Nivolumab plus ipilimumab showed promising efficacy for the treatment of non – small‐cell lung cancer ( NSCLC ) in a phase 1 trial , and tumor mutational burden has emerged as a potential biomarker of benefit . In this part of an open‐label , multipart , phase 3 trial , we examined progression‐free survival with nivolumab plus ipilimumab versus chemotherapy among patients with a high tumor mutational burden ( ≥10 mutations per megabase ) . METHODS We enrolled patients with stage IV or recurrent NSCLC that was not previously treated with chemotherapy . Those with a level of tumor programmed death lig and 1 ( PD‐L1 ) expression of at least 1 % were r and omly assigned , in a 1:1:1 ratio , to receive nivolumab plus ipilimumab , nivolumab monotherapy , or chemotherapy ; those with a tumor PD‐L1 expression level of less than 1 % were r and omly assigned , in a 1:1:1 ratio , to receive nivolumab plus ipilimumab , nivolumab plus chemotherapy , or chemotherapy . Tumor mutational burden was determined by the FoundationOne CDx assay . RESULTS Progression‐free survival among patients with a high tumor mutational burden was significantly longer with nivolumab plus ipilimumab than with chemotherapy . The 1‐year progression‐free survival rate was 42.6 % with nivolumab plus ipilimumab versus 13.2 % with chemotherapy , and the median progression‐free survival was 7.2 months ( 95 % confidence interval [ CI ] , 5.5 to 13.2 ) versus 5.5 months ( 95 % CI , 4.4 to 5.8 ) ( hazard ratio for disease progression or death , 0.58 ; 97.5 % CI , 0.41 to 0.81 ; P<0.001 ) . The objective response rate was 45.3 % with nivolumab plus ipilimumab and 26.9 % with chemotherapy . The benefit of nivolumab plus ipilimumab over chemotherapy was broadly consistent within subgroups , including patients with a PD‐L1 expression level of at least 1 % and those with a level of less than 1 % . The rate of grade 3 or 4 treatment‐related adverse events was 31.2 % with nivolumab plus ipilimumab and 36.1 % with chemotherapy . CONCLUSIONS Progression‐free survival was significantly longer with first‐line nivolumab plus ipilimumab than with chemotherapy among patients with NSCLC and a high tumor mutational burden , irrespective of PD‐L1 expression level . The results vali date the benefit of nivolumab plus ipilimumab in NSCLC and the role of tumor mutational burden as a biomarker for patient selection . ( Funded by Bristol‐Myers Squibb and Ono Pharmaceutical ; CheckMate 227 Clinical Trials.gov number , NCT02477826 . BACKGROUND Nivolumab , a fully human IgG4 programmed death 1 ( PD-1 ) immune-checkpoint-inhibitor antibody , disrupts PD-1-mediated signaling and may restore antitumor immunity . METHODS In this r and omized , open-label , international phase 3 study , we assigned patients with nonsquamous non-small-cell lung cancer ( NSCLC ) that had progressed during or after platinum-based doublet chemotherapy to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of 75 mg per square meter of body-surface area every 3 weeks . The primary end point was overall survival . RESULTS Overall survival was longer with nivolumab than with docetaxel . The median overall survival was 12.2 months ( 95 % confidence interval [ CI ] , 9.7 to 15.0 ) among 292 patients in the nivolumab group and 9.4 months ( 95 % CI , 8.1 to 10.7 ) among 290 patients in the docetaxel group ( hazard ratio for death , 0.73 ; 96 % CI , 0.59 to 0.89 ; P=0.002 ) . At 1 year , the overall survival rate was 51 % ( 95 % CI , 45 to 56 ) with nivolumab versus 39 % ( 95 % CI , 33 to 45 ) with docetaxel . With additional follow-up , the overall survival rate at 18 months was 39 % ( 95 % CI , 34 to 45 ) with nivolumab versus 23 % ( 95 % CI , 19 to 28 ) with docetaxel . The response rate was 19 % with nivolumab versus 12 % with docetaxel ( P=0.02 ) . Although progression-free survival did not favor nivolumab over docetaxel ( median , 2.3 months and 4.2 months , respectively ) , the rate of progression-free survival at 1 year was higher with nivolumab than with docetaxel ( 19 % and 8 % , respectively ) . Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression ( ≥1 % , ≥5 % , and ≥10 % ) of the PD-1 lig and . Treatment-related adverse events of grade 3 or 4 were reported in 10 % of the patients in the nivolumab group , as compared with 54 % of those in the docetaxel group . CONCLUSIONS Among patients with advanced nonsquamous NSCLC that had progressed during or after platinum-based chemotherapy , overall survival was longer with nivolumab than with docetaxel . ( Funded by Bristol-Myers Squibb ; CheckMate 057 Clinical Trials.gov number , NCT01673867 . ) BACKGROUND Nivolumab , a fully human IgG4 PD-1 immune checkpoint inhibitor antibody , can result in durable responses in patients with melanoma who have progressed after ipilimumab and BRAF inhibitors . We assessed the efficacy and safety of nivolumab compared with investigator 's choice of chemotherapy ( ICC ) as a second-line or later-line treatment in patients with advanced melanoma . METHODS In this r and omised , controlled , open-label , phase 3 trial , we recruited patients at 90 sites in 14 countries . Eligible patients were 18 years or older , had unresectable or metastatic melanoma , and progressed after ipilimumab , or ipilimumab and a BRAF inhibitor if they were BRAF(V 600 ) mutation-positive . Participating investigators r and omly assigned ( with an interactive voice response system ) patients 2:1 to receive an intravenous infusion of nivolumab 3 mg/kg every 2 weeks or ICC ( dacarbazine 1000 mg/m(2 ) every 3 weeks or paclitaxel 175 mg/m(2 ) combined with carboplatin area under the curve 6 every 3 weeks ) until progression or unacceptable toxic effects . We stratified r and omisation by BRAF mutation status , tumour expression of PD-L1 , and previous best overall response to ipilimumab . We used permuted blocks ( block size of six ) within each stratum . Primary endpoints were the proportion of patients who had an objective response and overall survival . Treatment was given open-label , but those doing tumour assessment s were masked to treatment assignment . We assessed objective responses per- protocol after 120 patients had been treated with nivolumab and had a minimum follow-up of 24 weeks , and safety in all patients who had had at least one dose of treatment . The trial is closed and this is the first interim analysis , reporting the objective response primary endpoint . This study is registered with Clinical Trials.gov , number NCT01721746 . FINDINGS Between Dec 21 , 2012 , and Jan 10 , 2014 , we screened 631 patients , r and omly allocating 272 patients to nivolumab and 133 to ICC . Confirmed objective responses were reported in 38 ( 31·7 % , 95 % CI 23·5 - 40·8 ) of the first 120 patients in the nivolumab group versus five ( 10·6 % , 3·5 - 23·1 ) of 47 patients in the ICC group . Grade 3 - 4 adverse events related to nivolumab included increased lipase ( three [ 1 % ] of 268 patients ) , increased alanine aminotransferase , anaemia , and fatigue ( two [ 1 % ] each ) ; for ICC , these included neutropenia ( 14 [ 14 % ] of 102 ) , thrombocytopenia ( six [ 6 % ] ) , and anaemia ( five [ 5 % ] ) . We noted grade 3 - 4 drug-related serious adverse events in 12 ( 5 % ) nivolumab-treated patients and nine ( 9 % ) patients in the ICC group . No treatment-related deaths occurred . INTERPRETATION Nivolumab led to a greater proportion of patients achieving an objective response and fewer toxic effects than with alternative available chemotherapy regimens for patients with advanced melanoma that has progressed after ipilimumab or ipilimumab and a BRAF inhibitor . Nivolumab represents a new treatment option with clinical ly meaningful durable objective responses in a population of high unmet need . FUNDING Bristol-Myers Squibb BACKGROUND Patients with advanced squamous-cell non-small-cell lung cancer ( NSCLC ) who have disease progression during or after first-line chemotherapy have limited treatment options . This r and omized , open-label , international , phase 3 study evaluated the efficacy and safety of nivolumab , a fully human IgG4 programmed death 1 ( PD-1 ) immune-checkpoint-inhibitor antibody , as compared with docetaxel in this patient population . METHODS We r and omly assigned 272 patients to receive nivolumab , at a dose of 3 mg per kilogram of body weight every 2 weeks , or docetaxel , at a dose of 75 mg per square meter of body-surface area every 3 weeks . The primary end point was overall survival . RESULTS The median overall survival was 9.2 months ( 95 % confidence interval [ CI ] , 7.3 to 13.3 ) with nivolumab versus 6.0 months ( 95 % CI , 5.1 to 7.3 ) with docetaxel . The risk of death was 41 % lower with nivolumab than with docetaxel ( hazard ratio , 0.59 ; 95 % CI , 0.44 to 0.79 ; P<0.001 ) . At 1 year , the overall survival rate was 42 % ( 95 % CI , 34 to 50 ) with nivolumab versus 24 % ( 95 % CI , 17 to 31 ) with docetaxel . The response rate was 20 % with nivolumab versus 9 % with docetaxel ( P=0.008 ) . The median progression-free survival was 3.5 months with nivolumab versus 2.8 months with docetaxel ( hazard ratio for death or disease progression , 0.62 ; 95 % CI , 0.47 to 0.81 ; P<0.001 ) . The expression of the PD-1 lig and ( PD-L1 ) was neither prognostic nor predictive of benefit . Treatment-related adverse events of grade 3 or 4 were reported in 7 % of the patients in the nivolumab group as compared with 55 % of those in the docetaxel group . CONCLUSIONS Among patients with advanced , previously treated squamous-cell NSCLC , overall survival , response rate , and progression-free survival were significantly better with nivolumab than with docetaxel , regardless of PD-L1 expression level . ( Funded by Bristol-Myers Squibb ; CheckMate 017 Clinical Trials.gov number , NCT01642004 . ) BACKGROUND Outcomes are poor for patients with previously treated , advanced or metastatic non-small-cell lung cancer ( NSCLC ) . The anti-programmed death lig and 1 ( PD-L1 ) antibody atezolizumab is clinical ly active against cancer , including NSCLC , especially cancers expressing PD-L1 on tumour cells , tumour-infiltrating immune cells , or both . We assessed efficacy and safety of atezolizumab versus docetaxel in previously treated NSCLC , analysed by PD-L1 expression levels on tumour cells and tumour-infiltrating immune cells and in the intention-to-treat population . METHODS In this open-label , phase 2 r and omised controlled trial , patients with NSCLC who progressed on post-platinum chemotherapy were recruited in 61 academic medical centres and community oncology practice s across 13 countries in Europe and North America . Key inclusion criteria were Eastern Cooperative Oncology Group performance status 0 or 1 , measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 ( RECIST v1.1 ) , and adequate haematological and end-organ function . Patients were stratified by PD-L1 tumour-infiltrating immune cell status , histology , and previous lines of therapy , and r and omly assigned ( 1:1 ) by permuted block r and omisation ( with a block size of four ) using an interactive voice or web system to receive intravenous atezolizumab 1200 mg or docetaxel 75 mg/m(2 ) once every 3 weeks . Baseline PD-L1 expression was scored by immunohistochemistry in tumour cells ( as percentage of PD-L1-expressing tumour cells TC3≥50 % , TC2≥5 % and < 50 % , TC1≥1 % and < 5 % , and TC0<1 % ) and tumour-infiltrating immune cells ( as percentage of tumour area : IC3≥10 % , IC2≥5 % and < 10 % , IC1≥1 % and < 5 % , and IC0<1 % ) . The primary endpoint was overall survival in the intention-to-treat population and PD-L1 subgroups at 173 deaths . Biomarkers were assessed in an exploratory analysis . We assessed safety in all patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT01903993 . FINDINGS Patients were enrolled between Aug 5 , 2013 , and March 31 , 2014 . 144 patients were r and omly allocated to the atezolizumab group , and 143 to the docetaxel group . 142 patients received at least one dose of atezolizumab and 135 received docetaxel . Overall survival in the intention-to-treat population was 12·6 months ( 95 % CI 9·7 - 16·4 ) for atezolizumab versus 9·7 months ( 8·6 - 12·0 ) for docetaxel ( hazard ratio [ HR ] 0·73 [ 95 % CI 0·53 - 0·99 ] ; p=0·04 ) . Increasing improvement in overall survival was associated with increasing PD-L1 expression ( TC3 or IC3 HR 0·49 [ 0·22 - 1·07 ; p=0·068 ] , TC2/3 or IC2/3 HR 0·54 [ 0·33 - 0·89 ; p=0·014 ] , TC1/2/3 or IC1/2/3 HR 0·59 [ 0·40 - 0·85 ; p=0·005 ] , TC0 and IC0 HR 1·04 [ 0·62 - 1·75 ; p=0·871 ] ) . In our exploratory analysis , patients with pre-existing immunity , defined by high T-effector-interferon-γ-associated gene expression , had improved overall survival with atezolizumab . 11 ( 8 % ) patients in the atezolizumab group discontinued because of adverse events versus 30 ( 22 % ) patients in the docetaxel group . 16 ( 11 % ) patients in the atezolizumab group versus 52 ( 39 % ) patients in the docetaxel group had treatment-related grade 3 - 4 adverse events , and one ( < 1 % ) patient in the atezolizumab group versus three ( 2 % ) patients in the docetaxel group died from a treatment-related adverse event . INTERPRETATION Atezolizumab significantly improved survival compared with docetaxel in patients with previously treated NSCLC . Improvement correlated with PD-L1 immunohistochemistry expression on tumour cells and tumour-infiltrating immune cells , suggesting that PD-L1 expression is predictive for atezolizumab benefit . Atezolizumab was well tolerated , with a safety profile distinct from chemotherapy . FUNDING F Hoffmann-La Roche/Genentech BACKGROUND Nivolumab was associated with higher rates of objective response than chemotherapy in a phase 3 study involving patients with ipilimumab-refractory metastatic melanoma . The use of nivolumab in previously untreated patients with advanced melanoma has not been tested in a phase 3 controlled study . METHODS We r and omly assigned 418 previously untreated patients who had metastatic melanoma without a BRAF mutation to receive nivolumab ( at a dose of 3 mg per kilogram of body weight every 2 weeks and dacarbazine-matched placebo every 3 weeks ) or dacarbazine ( at a dose of 1000 mg per square meter of body-surface area every 3 weeks and nivolumab-matched placebo every 2 weeks ) . The primary end point was overall survival . RESULTS At 1 year , the overall rate of survival was 72.9 % ( 95 % confidence interval [ CI ] , 65.5 to 78.9 ) in the nivolumab group , as compared with 42.1 % ( 95 % CI , 33.0 to 50.9 ) in the dacarbazine group ( hazard ratio for death , 0.42 ; 99.79 % CI , 0.25 to 0.73 ; P<0.001 ) . The median progression-free survival was 5.1 months in the nivolumab group versus 2.2 months in the dacarbazine group ( hazard ratio for death or progression of disease , 0.43 ; 95 % CI , 0.34 to 0.56 ; P<0.001 ) . The objective response rate was 40.0 % ( 95 % CI , 33.3 to 47.0 ) in the nivolumab group versus 13.9 % ( 95 % CI , 9.5 to 19.4 ) in the dacarbazine group ( odds ratio , 4.06 ; P<0.001 ) . The survival benefit with nivolumab versus dacarbazine was observed across prespecified subgroups , including subgroups defined by status regarding the programmed death lig and 1 ( PD-L1 ) . Common adverse events associated with nivolumab included fatigue , pruritus , and nausea . Drug-related adverse events of grade 3 or 4 occurred in 11.7 % of the patients treated with nivolumab and 17.6 % of those treated with dacarbazine . CONCLUSIONS Nivolumab was associated with significant improvements in overall survival and progression-free survival , as compared with dacarbazine , among previously untreated patients who had metastatic melanoma without a BRAF mutation . ( Funded by Bristol-Myers Squibb ; CheckMate 066 Clinical Trials.gov number , NCT01721772 . ) Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND Pembrolizumab is a humanized monoclonal antibody against programmed death 1 ( PD-1 ) that has antitumor activity in advanced non-small-cell lung cancer ( NSCLC ) , with increased activity in tumors that express programmed death lig and 1 ( PD-L1 ) . METHODS In this open-label , phase 3 trial , we r and omly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50 % of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab ( at a fixed dose of 200 mg every 3 weeks ) or the investigator 's choice of platinum-based chemotherapy . Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression . The primary end point , progression-free survival , was assessed by means of blinded , independent , central radiologic review . Secondary end points were overall survival , objective response rate , and safety . RESULTS Median progression-free survival was 10.3 months ( 95 % confidence interval [ CI ] , 6.7 to not reached ) in the pembrolizumab group versus 6.0 months ( 95 % CI , 4.2 to 6.2 ) in the chemotherapy group ( hazard ratio for disease progression or death , 0.50 ; 95 % CI , 0.37 to 0.68 ; P<0.001 ) . The estimated rate of overall survival at 6 months was 80.2 % in the pembrolizumab group versus 72.4 % in the chemotherapy group ( hazard ratio for death , 0.60 ; 95 % CI , 0.41 to 0.89 ; P=0.005 ) . The response rate was higher in the pembrolizumab group than in the chemotherapy group ( 44.8 % vs. 27.8 % ) , the median duration of response was longer ( not reached [ range , 1.9 + to 14.5 + months ] vs. 6.3 months [ range , 2.1 + to 12.6 + ] ) , and treatment-related adverse events of any grade were less frequent ( occurring in 73.4 % vs. 90.0 % of patients ) , as were grade 3 , 4 , or 5 treatment-related adverse events ( 26.6 % vs. 53.3 % ) . CONCLUSIONS In patients with advanced NSCLC and PD-L1 expression on at least 50 % of tumor cells , pembrolizumab was associated with significantly longer progression-free and overall survival and with fewer adverse events than was platinum-based chemotherapy . ( Funded by Merck ; KEYNOTE-024 Clinical Trials.gov number , NCT02142738 . ) Purpose Until recently , limited options existed for patients with advanced melanoma who experienced disease progression while receiving treatment with ipilimumab . Here , we report the co primary overall survival ( OS ) end point of CheckMate 037 , which has previously shown that nivolumab result ed in more patients achieving an objective response compared with chemotherapy regimens in ipilimumab-refractory patients with advanced melanoma . Patients and Methods Patients were stratified by programmed death-lig and 1 expression , BRAF status , and best prior cytotoxic T-lymphocyte antigen-4 therapy response , then r and omly assigned 2:1 to nivolumab 3 mg/kg intravenously every 2 weeks or investigator 's choice chemotherapy ( ICC ; dacarbazine 1,000 mg/m2 every 3 weeks or carboplatin area under the curve 6 plus paclitaxel 175 mg/m2 every 3 weeks ) . Patients were treated until they experienced progression or unacceptable toxicity , with follow-up of approximately 2 years . Results Two hundred seventy-two patients were r and omly assigned to nivolumab ( 99 % treated ) and 133 to ICC ( 77 % treated ) . More nivolumab-treated patients had brain metastases ( 20 % v 14 % ) and increased lactate dehydrogenase levels ( 52 % v 38 % ) at baseline ; 41 % of patients treated with ICC versus 11 % of patients treated with nivolumab received anti-programmed death 1 agents after r and omly assigned therapy . Median OS was 16 months for nivolumab versus 14 months for ICC ( hazard ratio , 0.95 ; 95.54 % CI , 0.73 to 1.24 ) ; median progression-free survival was 3.1 months versus 3.7 months , respectively ( hazard ratio , 1.0 ; 95.1 % CI , 0.78 to 1.436 ) . Overall response rate ( 27 % v 10 % ) and median duration of response ( 32 months v 13 months ) were notably higher for nivolumab versus ICC . Fewer grade 3 and 4 treatment-related adverse events were observed in patients on nivolumab ( 14 % v 34 % ) . Conclusion Nivolumab demonstrated higher , more durable responses but no difference in survival compared with ICC . OS should be interpreted with caution as it was likely impacted by an increased dropout rate before treatment , which led to crossover therapy in the ICC group , and by an increased proportion of patients in the nivolumab group with poor prognostic factors BACKGROUND Despite recent advances in the treatment of advanced non-small-cell lung cancer , there remains a need for effective treatments for progressive disease . We assessed the efficacy of pembrolizumab for patients with previously treated , PD-L1-positive , advanced non-small-cell lung cancer . METHODS We did this r and omised , open-label , phase 2/3 study at 202 academic medical centres in 24 countries . Patients with previously treated non-small-cell lung cancer with PD-L1 expression on at least 1 % of tumour cells were r and omly assigned ( 1:1:1 ) in blocks of six per stratum with an interactive voice-response system to receive pembrolizumab 2 mg/kg , pembrolizumab 10 mg/kg , or docetaxel 75 mg/m(2 ) every 3 weeks . The primary endpoints were overall survival and progression-free survival both in the total population and in patients with PD-L1 expression on at least 50 % of tumour cells . We used a threshold for significance of p<0.00825 ( one-sided ) for the analysis of overall survival and a threshold of p<0.001 for progression-free survival . This trial is registered at Clinical Trials.gov , number NCT01905657 . FINDINGS Between Aug 28 , 2013 , and Feb 27 , 2015 , we enrolled 1034 patients : 345 allocated to pembrolizumab 2 mg/kg , 346 allocated to pembrolizumab 10 mg/kg , and 343 allocated to docetaxel . By Sept 30 , 2015 , 521 patients had died . In the total population , median overall survival was 10.4 months with pembrolizumab 2 mg/kg , 12.7 months with pembrolizumab 10 mg/kg , and 8.5 months with docetaxel . Overall survival was significantly longer for pembrolizumab 2 mg/kg versus docetaxel ( hazard ratio [ HR ] 0.71 , 95 % CI 0.58 - 0.88 ; p=0.0008 ) and for pembrolizumab 10 mg/kg versus docetaxel ( 0.61 , 0.49 - 0.75 ; p<0.0001 ) . Median progression-free survival was 3.9 months with pembrolizumab 2 mg/kg , 4.0 months with pembrolizumab 10 mg/kg , and 4.0 months with docetaxel , with no significant difference for pembrolizumab 2 mg/kg versus docetaxel ( 0.88 , 0.74 - 1.05 ; p=0.07 ) or for pembrolizumab 10 mg/kg versus docetaxel ( HR 0.79 , 95 % CI 0.66 - 0.94 ; p=0.004 ) . Among patients with at least 50 % of tumour cells expressing PD-L1 , overall survival was significantly longer with pembrolizumab 2 mg/kg than with docetaxel ( median 14.9 months vs 8.2 months ; HR 0.54 , 95 % CI 0.38 - 0.77 ; p=0.0002 ) and with pembrolizumab 10 mg/kg than with docetaxel ( 17.3 months vs 8.2 months ; 0.50 , 0.36 - 0.70 ; p<0.0001 ) . Likewise , for this patient population , progression-free survival was significantly longer with pembrolizumab 2 mg/kg than with docetaxel ( median 5.0 months vs 4.1 months ; HR 0.59 , 95 % CI 0.44 - 0.78 ; p=0.0001 ) and with pembrolizumab 10 mg/kg than with docetaxel ( 5.2 months vs 4.1 months ; 0.59 , 0.45 - 0.78 ; p<0.0001 ) . Grade 3 - 5 treatment-related adverse events were less common with pembrolizumab than with docetaxel ( 43 [ 13 % ] of 339 patients given 2 mg/kg , 55 [ 16 % ] of 343 given 10 mg/kg , and 109 [ 35 % ] of 309 given docetaxel ) . INTERPRETATION Pembrolizumab prolongs overall survival and has a favourable benefit-to-risk profile in patients with previously treated , PD-L1-positive , advanced non-small-cell lung cancer . These data establish pembrolizumab as a new treatment option for this population and vali date the use of PD-L1 selection . FUNDING Merck & BACKGROUND Patients with melanoma that progresses on ipilimumab and , if BRAF(V600 ) mutant-positive , a BRAF or MEK inhibitor or both , have few treatment options . We assessed the efficacy and safety of two pembrolizumab doses versus investigator-choice chemotherapy in patients with ipilimumab-refractory melanoma . METHODS We carried out a r and omised phase 2 trial of patients aged 18 years or older from 73 hospitals , clinics , and academic medical centres in 12 countries who had confirmed progressive disease within 24 weeks after two or more ipilimumab doses and , if BRAF(V600 ) mutant-positive , previous treatment with a BRAF or MEK inhibitor or both . Patients had to have resolution of all ipilimumab-related adverse events to grade 0 - 1 and prednisone 10 mg/day or less for at least 2 weeks , an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 or 1 , and at least one measurable lesion to be eligible . Using a central ised interactive voice response system , we r and omly assigned ( 1:1:1 ) patients in a block size of six to receive intravenous pembrolizumab 2 mg/kg or 10 mg/kg every 3 weeks or investigator-choice chemotherapy ( paclitaxel plus carboplatin , paclitaxel , carboplatin , dacarbazine , or oral temozolomide ) . R and omisation was stratified by ECOG performance status , lactate dehydrogenase concentration , and BRAF(V600 ) mutation status . Individual treatment assignment between pembrolizumab and chemotherapy was open label , but investigators and patients were masked to assignment of the dose of pembrolizumab . We present the primary endpoint at the prespecified second interim analysis of progression-free survival in the intention-to-treat population . This study is registered with Clinical Trials.gov , number NCT01704287 . The study is closed to enrolment but continues to follow up and treat patients . FINDINGS Between Nov 30 , 2012 , and Nov 13 , 2013 , we enrolled 540 patients : 180 patients were r and omly assigned to receive pembrolizumab 2 mg/kg , 181 to receive pembrolizumab 10 mg/kg , and 179 to receive chemotherapy . Based on 410 progression-free survival events , progression-free survival was improved in patients assigned to pembrolizumab 2 mg/kg ( HR 0·57 , 95 % CI 0·45 - 0·73 ; p<0·0001 ) and those assigned to pembrolizumab 10 mg/kg ( 0·50 , 0·39 - 0·64 ; p<0·0001 ) compared with those assigned to chemotherapy . 6-month progression-free survival was 34 % ( 95 % CI 27 - 41 ) in the pembrolizumab 2 mg/kg group , 38 % ( 31 - 45 ) in the 10 mg/kg group , and 16 % ( 10 - 22 ) in the chemotherapy group . Treatment-related grade 3 - 4 adverse events occurred in 20 ( 11 % ) patients in the pembrolizumab 2 mg/kg group , 25 ( 14 % ) in the pembrolizumab 10 mg/kg group , and 45 ( 26 % ) in the chemotherapy group . The most common treatment-related grade 3 - 4 adverse event in the pembrolizumab groups was fatigue ( two [ 1 % ] of 178 patients in the 2 mg/kg group and one [ < 1 % ] of 179 patients in the 10 mg/kg group , compared with eight [ 5 % ] of 171 in the chemotherapy group ) . Other treatment-related grade 3 - 4 adverse events include generalised oedema and myalgia ( each in two [ 1 % ] patients ) in those given pembrolizumab 2 mg/kg ; hypopituitarism , colitis , diarrhoea , decreased appetite , hyponatremia , and pneumonitis ( each in two [ 1 % ] ) in those given pembrolizumab 10 mg/kg ; and anaemia ( nine [ 5 % ] ) , fatigue ( eight [ 5 % ] ) , neutropenia ( six [ 4 % ] ) , and leucopenia ( six [ 4 % ] ) in those assigned to chemotherapy . INTERPRETATION These findings establish pembrolizumab as a new st and ard of care for the treatment of ipilimumab-refractory melanoma . FUNDING Merck Sharp & Dohme BACKGROUND Patients with advanced gastric or gastro-oesophageal junction cancer refractory to , or intolerant of , two or more previous regimens of chemotherapy have a poor prognosis , and current guidelines do not recommend any specific treatments for these patients . We assessed the efficacy and safety of nivolumab , a fully human IgG4 monoclonal antibody inhibitor of programmed death-1 ( PD-1 ) , in patients with advanced gastric or gastro-oesophageal junction cancer who had been previously been treated with two or more chemotherapy regimens . METHODS In this r and omised , double-blind , placebo-controlled , phase 3 trial done at 49 clinical sites in Japan , South Korea , and Taiwan , eligible patients ( aged ≥20 years with unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer refractory to , or intolerant of , st and ard therapy [ including two or more previous chemotherapy regimens ] , with an Eastern Cooperative Oncology Group [ ECOG ] performance status of 0 - 1 , and naive to anti-PD-1 therapy or other therapeutic antibodies and pharmacotherapies for the regulation of T cells ) were recruited . Patients were r and omly assigned ( 2:1 ) using an interactive web response system to receive 3 mg/kg nivolumab or placebo intravenously every 2 weeks , stratified by country , ECOG performance status , and number of organs with metastases . Study treatment was continued until progressive disease per investigator assessment or onset of toxicities requiring permanent discontinuation . Patients and investigators were masked to group assignment . The primary endpoint was overall survival in the intention-to-treat population . Safety was analysed in all patients who received at least one dose of study treatment . This study is ongoing but not recruiting new patients , and is registered with Clinical Trials.gov , number NCT02267343 . FINDINGS Between Nov 4 , 2014 , and Feb 26 , 2016 , we r and omly assigned 493 patients to receive nivolumab ( n=330 ) or placebo ( n=163 ) . At the data cutoff ( Aug 13 , 2016 ) , median follow-up in surviving patients was 8·87 months ( IQR 6·57 - 12·37 ) in the nivolumab group and 8·59 months ( 5·65 - 11·37 ) in the placebo group . Median overall survival was 5·26 months ( 95 % CI 4·60 - 6·37 ) in the nivolumab group and 4·14 months ( 3·42 - 4·86 ) in the placebo group ( hazard ratio 0·63 , 95 % CI 0·51 - 0·78 ; p<0·0001 ) . 12-month overall survival rates were 26·2 % ( 95 % CI 20·7 - 32·0 ) with nivolumab and 10·9 % ( 6·2 - 17·0 ) with placebo . Grade 3 or 4 treatment-related adverse events occurred in 34 ( 10 % ) of 330 patients who received nivolumab and seven ( 4 % ) of 161 patients who received placebo ; treatment-related adverse events led to death in five ( 2 % ) of 330 patients in the nivolumab group and two ( 1 % ) of 161 patients in the placebo group . No new safety signals were observed . INTERPRETATION In this phase 3 study , the survival benefits indicate that nivolumab might be a new treatment option for heavily pretreated patients with advanced gastric or gastro-oesophageal junction cancer . Ongoing trials that include non-Asian patients are investigating nivolumab for advanced gastric or gastro-oesophageal junction cancer in various setting s and earlier treatment lines . FUNDING Ono Pharmaceutical and Bristol-Myers Squibb BACKGROUND Patients with advanced gastric or gastro-oesophageal junction cancer that progresses on chemotherapy have poor outcomes . We compared pembrolizumab with paclitaxel in patients with advanced gastric or gastro-oesophageal junction cancer that progressed on first-line chemotherapy with a platinum and fluoropyrimidine . METHODS This r and omised , open-label , phase 3 study was done at 148 medical centres in 30 countries . Eligible patients were r and omised ( 1:1 ) in blocks of four per stratum with an interactive voice-response and integrated web-response system to receive either pembrolizumab 200 mg every 3 weeks for up to 2 years or st and ard-dose paclitaxel . Primary endpoints were overall survival and progression-free survival in patients with a programmed cell death lig and 1 ( PD-L1 ) combined positive score ( CPS ) of 1 or higher . Safety was assessed in all patients , irrespective of CPS . The significance threshold for overall survival was p=0·0135 ( one-sided ) . This trial is registered at Clinical Trials.gov , number NCT02370498 . FINDINGS Between June 4 , 2015 , and July 26 , 2016 , 592 patients were enrolled . Of the 395 patients who had a PD-L1 CPS of 1 or higher , 196 patients were assigned to receive pembrolizumab and 199 patients were assigned to receive paclitaxel . As of Oct 26 , 2017 , 326 patients in the population with CPS of 1 or higher had died ( 151 [ 77 % ] of 196 patients in the pembrolizumab group and 175 [ 88 % ] of 199 patients in the paclitaxel group ) . Median overall survival was 9·1 months ( 95 % CI 6·2 - 10·7 ) with pembrolizumab and 8·3 months ( 7·6 - 9·0 ) with paclitaxel ( hazard ratio [ HR ] 0·82 , 95 % CI 0·66 - 1·03 ; one-sided p=0·0421 ) . Median progression-free survival was 1·5 months ( 95 % CI 1·4 - 2·0 ) with pembrolizumab and 4·1 months ( 3·1 - 4·2 ) with paclitaxel ( HR 1·27 , 95 % CI 1·03 - 1·57 ) . In the total population , grade 3 - 5 treatment-related adverse events occurred in 42 ( 14 % ) of the 294 patients treated with pembrolizumab and 96 ( 35 % ) of the 276 patients treated with paclitaxel . INTERPRETATION Pembrolizumab did not significantly improve overall survival compared with paclitaxel as second-line therapy for advanced gastric or gastro-oesophageal junction cancer with PD-L1 CPS of 1 or higher . Pembrolizumab had a better safety profile than paclitaxel . Additional trials of pembrolizumab in gastric and gastro-oesophageal cancer are ongoing . FUNDING Merck Sharp & Dohme , a subsidiary of Merck & Background St and ard first‐line therapy for metastatic , squamous non – small‐cell lung cancer ( NSCLC ) is platinum‐based chemotherapy or pembrolizumab ( for patients with programmed death lig and 1 [ PD‐L1 ] expression on ≥50 % of tumor cells ) . More recently , pembrolizumab plus chemotherapy was shown to significantly prolong overall survival among patients with nonsquamous NSCLC . Methods In this double‐blind , phase 3 trial , we r and omly assigned , in a 1:1 ratio , 559 patients with untreated metastatic , squamous NSCLC to receive 200 mg of pembrolizumab or saline placebo for up to 35 cycles ; all the patients also received carboplatin and either paclitaxel or nanoparticle albumin‐bound [nab]–paclitaxel for the first 4 cycles . Primary end points were overall survival and progression‐free survival . Results After a median follow‐up of 7.8 months , the median overall survival was 15.9 months ( 95 % confidence interval [ CI ] , 13.2 to not reached ) in the pembrolizumab‐combination group and 11.3 months ( 95 % CI , 9.5 to 14.8 ) in the placebo‐combination group ( hazard ratio for death , 0.64 ; 95 % CI , 0.49 to 0.85 ; P<0.001 ) . The overall survival benefit was consistent regardless of the level of PD‐L1 expression . The median progression‐free survival was 6.4 months ( 95 % CI , 6.2 to 8.3 ) in the pembrolizumab‐combination group and 4.8 months ( 95 % CI , 4.3 to 5.7 ) in the placebo‐combination group ( hazard ratio for disease progression or death , 0.56 ; 95 % CI , 0.45 to 0.70 ; P<0.001 ) . Adverse events of grade 3 or higher occurred in 69.8 % of the patients in the pembrolizumab‐combination group and in 68.2 % of the patients in the placebo‐combination group . Discontinuation of treatment because of adverse events was more frequent in the pembrolizumab‐combination group than in the placebo‐combination group ( 13.3 % vs. 6.4 % ) . Conclusions In patients with previously untreated metastatic , squamous NSCLC , the addition of pembrolizumab to chemotherapy with carboplatin plus paclitaxel or nab‐paclitaxel result ed in significantly longer overall survival and progression‐free survival than chemotherapy alone . ( Funded by Merck Sharp & Dohme ; KEYNOTE‐407 Clinical Trials.gov number , NCT02775435 . BACKGROUND An earlier analysis in this phase 3 trial showed that durvalumab significantly prolonged progression‐free survival , as compared with placebo , among patients with stage III , unresectable non – small‐cell lung cancer ( NSCLC ) who did not have disease progression after concurrent chemoradiotherapy . Here we report the results for the second primary end point of overall survival . METHODS We r and omly assigned patients , in a 2:1 ratio , to receive durvalumab intravenously , at a dose of 10 mg per kilogram of body weight , or matching placebo every 2 weeks for up to 12 months . R and omization occurred 1 to 42 days after the patients had received chemoradiotherapy and was stratified according to age , sex , and smoking history . The primary end points were progression‐free survival ( as assessed by blinded independent central review ) and overall survival . Secondary end points included the time to death or distant metastasis , the time to second progression , and safety . RESULTS Of the 713 patients who underwent r and omization , 709 received the assigned intervention ( 473 patients received durvalumab and 236 received placebo ) . As of March 22 , 2018 , the median follow‐up was 25.2 months . The 24‐month overall survival rate was 66.3 % ( 95 % confidence interval [ CI ] , 61.7 to 70.4 ) in the durvalumab group , as compared with 55.6 % ( 95 % CI , 48.9 to 61.8 ) in the placebo group ( two‐sided P=0.005 ) . Durvalumab significantly prolonged overall survival , as compared with placebo ( stratified hazard ratio for death , 0.68 ; 99.73 % CI , 0.47 to 0.997 ; P=0.0025 ) . Up date d analyses regarding progression‐free survival were similar to those previously reported , with a median duration of 17.2 months in the durvalumab group and 5.6 months in the placebo group ( stratified hazard ratio for disease progression or death , 0.51 ; 95 % CI , 0.41 to 0.63 ) . The median time to death or distant metastasis was 28.3 months in the durvalumab group and 16.2 months in the placebo group ( stratified hazard ratio , 0.53 ; 95 % CI , 0.41 to 0.68 ) . A total of 30.5 % of the patients in the durvalumab group and 26.1 % of those in the placebo group had grade 3 or 4 adverse events of any cause ; 15.4 % and 9.8 % of the patients , respectively , discontinued the trial regimen because of adverse events . CONCLUSIONS Durvalumab therapy result ed in significantly longer overall survival than placebo . No new safety signals were identified . ( Funded by AstraZeneca ; PACIFIC Clinical Trials.gov number , NCT02125461 . Importance This analysis provides long-term follow-up in patients with BRAF wild-type advanced melanoma receiving first-line therapy based on anti – programmed cell death 1 receptor inhibitors . Objective To compare the 3-year survival with nivolumab vs that with dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma . Design , Setting , and Participants This follow-up of a r and omized phase 3 trial analyzed 3-year overall survival data from the r and omized , controlled , double-blind CheckMate 066 phase 3 clinical trial . For this ongoing , multicenter academic institution trial , patients were enrolled from January 2013 through February 2014 . Eligible patients were 18 years or older with confirmed unresectable previously untreated stage III or IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 but without a BRAF mutation . Interventions Patients were treated until progression or unacceptable toxic events with nivolumab ( 3 mg/kg every 2 weeks plus dacarbazine-matched placebo every 3 weeks ) or dacarbazine ( 1000 mg/m2 every 3 weeks plus nivolumab-matched placebo every 2 weeks ) . Main Outcome and Measure Overall survival . Results At minimum follow-ups of 38.4 months among 210 participants in the nivolumab group ( median age , 64 years [ range , 18 - 86 years ] ; 57.6 % male ) and 38.5 months among 208 participants in the dacarbazine group ( median age , 66 years [ range , 25 - 87 years ] ; 60.1 % male ) , 3-year overall survival rates were 51.2 % ( 95 % CI , 44.1%-57.9 % ) and 21.6 % ( 95 % CI , 16.1%-27.6 % ) , respectively . The median overall survival was 37.5 months ( 95 % CI , 25.5 months – not reached ) in the nivolumab group and 11.2 months ( 95 % CI , 9.6 - 13.0 months ) in the dacarbazine group ( hazard ratio , 0.46 ; 95 % CI , 0.36 - 0.59 ; P < .001 ) . Complete and partial responses , respectively , were reported for 19.0 % ( 40 of 210 ) and 23.8 % ( 50 of 210 ) of patients in the nivolumab group compared with 1.4 % ( 3 of 208 ) and 13.0 % ( 27 of 208 ) of patients in the dacarbazine group . Additional analyses were performed on outcomes with subsequent therapies . Treatment-related grade 3/4 adverse events occurred in 15.0 % ( 31 of 206 ) of nivolumab-treated patients and in 17.6 % ( 36 of 205 ) of dacarbazine-treated patients . There were no deaths due to study drug toxic effects . Conclusions and Relevance Nivolumab led to improved 3-year overall survival vs dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma . Trial Registration Clinical Trials.gov identifier : Background Patients with advanced urothelial carcinoma that progresses after platinum‐based chemotherapy have a poor prognosis and limited treatment options . Methods In this open‐label , international , phase 3 trial , we r and omly assigned 542 patients with advanced urothelial cancer that recurred or progressed after platinum‐based chemotherapy to receive pembrolizumab ( a highly selective , humanized monoclonal IgG4κ isotype antibody against programmed death 1 [ PD‐1 ] ) at a dose of 200 mg every 3 weeks or the investigator 's choice of chemotherapy with paclitaxel , docetaxel , or vinflunine . The co primary end points were overall survival and progression‐free survival , which were assessed among all patients and among patients who had a tumor PD‐1 lig and ( PD‐L1 ) combined positive score ( the percentage of PD‐L1–expressing tumor and infiltrating immune cells relative to the total number of tumor cells ) of 10 % or more . Results The median overall survival in the total population was 10.3 months ( 95 % confidence interval [ CI ] , 8.0 to 11.8 ) in the pembrolizumab group , as compared with 7.4 months ( 95 % CI , 6.1 to 8.3 ) in the chemotherapy group ( hazard ratio for death , 0.73 ; 95 % CI , 0.59 to 0.91 ; P=0.002 ) . The median overall survival among patients who had a tumor PD‐L1 combined positive score of 10 % or more was 8.0 months ( 95 % CI , 5.0 to 12.3 ) in the pembrolizumab group , as compared with 5.2 months ( 95 % CI , 4.0 to 7.4 ) in the chemotherapy group ( hazard ratio , 0.57 ; 95 % CI , 0.37 to 0.88 ; P=0.005 ) . There was no significant between‐group difference in the duration of progression‐free survival in the total population ( hazard ratio for death or disease progression , 0.98 ; 95 % CI , 0.81 to 1.19 ; P=0.42 ) or among patients who had a tumor PD‐L1 combined positive score of 10 % or more ( hazard ratio , 0.89 ; 95 % CI , 0.61 to 1.28 ; P=0.24 ) . Fewer treatment‐related adverse events of any grade were reported in the pembrolizumab group than in the chemotherapy group ( 60.9 % vs. 90.2 % ) ; there were also fewer events of grade 3 , 4 , or 5 severity reported in the pembrolizumab group than in the chemotherapy group ( 15.0 % vs. 49.4 % ) . Conclusions Pembrolizumab was associated with significantly longer overall survival ( by approximately 3 months ) and with a lower rate of treatment‐related adverse events than chemotherapy as second‐line therapy for platinum‐refractory advanced urothelial carcinoma . ( Funded by Merck ; KEYNOTE‐045 Clinical Trials.gov number , NCT02256436 . BACKGROUND Enhancing tumor‐specific T‐cell immunity by inhibiting programmed death lig and 1 (PD‐L1)–programmed death 1 ( PD‐1 ) signaling has shown promise in the treatment of extensive‐stage small‐cell lung cancer . Combining checkpoint inhibition with cytotoxic chemotherapy may have a synergistic effect and improve efficacy . METHODS We conducted this double‐blind , placebo‐controlled , phase 3 trial to evaluate atezolizumab plus carboplatin and etoposide in patients with extensive‐stage small‐cell lung cancer who had not previously received treatment . Patients were r and omly assigned in a 1:1 ratio to receive carboplatin and etoposide with either atezolizumab or placebo for four 21‐day cycles ( induction phase ) , followed by a maintenance phase during which they received either atezolizumab or placebo ( according to the previous r and om assignment ) until they had unacceptable toxic effects , disease progression according to Response Evaluation Criteria in Solid Tumors , version 1.1 , or no additional clinical benefit . The two primary end points were investigator‐assessed progression‐free survival and overall survival in the intention‐to‐treat population . RESULTS A total of 201 patients were r and omly assigned to the atezolizumab group , and 202 patients to the placebo group . At a median follow‐up of 13.9 months , the median overall survival was 12.3 months in the atezolizumab group and 10.3 months in the placebo group ( hazard ratio for death , 0.70 ; 95 % confidence interval [ CI ] , 0.54 to 0.91 ; P=0.007 ) . The median progression‐free survival was 5.2 months and 4.3 months , respectively ( hazard ratio for disease progression or death , 0.77 ; 95 % CI , 0.62 to 0.96 ; P=0.02 ) . The safety profile of atezolizumab plus carboplatin and etoposide was consistent with the previously reported safety profile of the individual agents , with no new findings observed . CONCLUSIONS The addition of atezolizumab to chemotherapy in the first‐line treatment of extensive‐stage small‐cell lung cancer result ed in significantly longer overall survival and progression‐free survival than chemotherapy alone . ( Funded by F. Hoffmann – La Roche/Genentech ; IMpower133 Clinical Trials.gov number , NCT02763579 . |
12,992 | 18,843,620 | These compared day hospital with a ) comprehensive elderly care ( five trials ) , b ) domiciliary care ( five trials ) , or c ) no comprehensive elderly care ( three trials).There were no significant differences between day hospital attendance and the sub-categories of comparison treatments for the outcomes of death , death or requiring institutional care , death or deterioration in ADL .
Using the outcome of deterioration in ADL among survivors , day hospital patients showed a reduced odds of deterioration when compared with those receiving no comprehensive elderly care ( OR 0.60 ; 95 % CI 0.38 to 0.97 ; P < 0.05).When re source use was examined the day hospital group showed trends towards reductions in hospital bed use and placement of survivors in institutional care .
Medical day hospital care for the elderly appears to be more effective than no intervention but may have no clear advantage over other forms of comprehensive elderly medical services | BACKGROUND The proportion of the world 's population aged 60 or over is increasing .
This review sets out to examine the effectiveness and re source implication s of geriatric medical day hospital attendance for elderly people .
This is an up date of a Cochrane review first published in 1999 .
OBJECTIVES To examine the effectiveness of attendance at a medical day hospital for elderly people in preventing death , disability , and institutionalisation and improving subjective health status . | The purpose of this study was to examine the impact of geriatric day care and homemaker services on patient outcomes . Patients were r and omly assigned to receive the experimental services in three study sample s. In comparing outcomes between the experimental and control groups , it was found that there were significant differences in physical functioning and activity level for the day care sample s , in physical functioning and contentment level for the homemaker study sample , and in all of these outcome measures for the combined services group . Among users of the experimental services , increased use of the services was associated with improved outcomes of care . Multivariate analysis of data showed that factors other than the use of the experimental services were more effective in explaining variation in outcomes . Significant factors that affected all four outcome measures in both the day care and homemaker study were primary diagnosis , impairment prognosis , and number of inpatient hospital days The effectiveness and cost of day hospital care in rehabilitation were studied in a r and omised controlled trial in 120 elderly patients who were assessed at referral and six weeks and five months later in activities of daily living skills and mood . Day hospital patients were compared with a control group , who were managed as they would have been before the availability of day hospital care . Day hospital patients showed a significant improvement in performance of activities of daily living at six weeks but not at five months ; however , they had a sustained improvement in mood . The cost of day hospital rehabilitation was one third greater than that of rehabilitation by alternative means . In its current form the geriatric day hospital is not a cheap alternative to other means of rehabilitation . Expensive components of the day hospital should be critically re-examined and renewed emphasis placed on sufficient inpatient beds , domiciliary services , and day care centres OBJECTIVE To determine whether a new model of primary care , Chronic Care Clinics , can improve outcomes of common geriatric syndromes ( urinary incontinence , falls , depressive symptoms , high risk medications , functional impairment ) in frail older adults . DESIGN R and omized controlled trial with 24 months of follow-up . Physician practice s were r and omized either to the Chronic Care Clinics intervention or to usual care . SETTING Nine primary care physician practice s that comprise an ambulatory clinic in a large staff-model HMO in western Washington State . PARTICIPANTS Those patients aged 65 and older in each practice with the highest risk for being hospitalized or experiencing functional decline . INTERVENTION Intervention practice s ( 5 physicians , 96 patients ) held half-day Chronic Care Clinics every 3 to 4 months . These clinics included an extended visit with the physician and nurse dedicated to planning chronic disease management ; a pharmacist visit that emphasized reduction of polypharmacy and high-risk medications ; and a patient self-management/support group . Control practice s ( 4 physicians , 73 patients ) received usual care . MEASUREMENTS Changes in self-reported urinary incontinence , frequency of falls , depressive symptoms , physical function , and satisfaction were analyzed using an intention-to-treat analysis adjusted for baseline differences , covariates , and practice -level variation . Prescriptions for high-risk medications and cost/utilization data obtained from administrative data were similarly analyzed . RESULTS After 24 months , no significant improvements in frequency of incontinence , proportion with falls , depression scores , physical function scores , or prescriptions for high risk medications were demonstrated . Costs of medical care including frequency of hospitalization , hospital days , emergency and ambulatory visits , and total costs of care were not significantly different between intervention and control groups . A higher proportion of intervention patients rated the overall quality of their medical care as excellent compared with control patients ( 40.0 % vs 25.3 % , P = .10 ) . CONCLUSIONS Although intervention patients expressed high levels of satisfaction with Chronic Care Clinics , improved outcomes for selected geriatric syndromes were not demonstrated . These findings suggest the need for developing greater system-wide support for managing geriatric syndromes in primary care and illustrate the challenges of conducting practice improvement research in a rapidly changing delivery system Falls in older people are a major public health concern in terms of morbidity , mortality and cost . Previous studies suggest that multifactorial interventions can reduce falls , and many geriatric day hospitals are now offering falls intervention programmes . However , no studies have investigated whether these programmes , based in the day hospital are effective , nor whether they can be successfully applied to high-risk older people screened in primary care . The hypothesis is that a multidisciplinary falls assessment and intervention at Day hospitals can reduce the incidence of falls in older people identified within primary care as being at high risk of falling . This will be tested by a pragmatic parallel-group r and omised controlled trial in which the participants , identified as at high risk of falling , will be r and omised into either the intervention Day hospital arm or to a control ( current practice ) arm . Those participants preferring not to enter the full r and omised study will be offered the opportunity to complete brief diaries only at monthly intervals . This data will be used to vali date the screening question naire . Three day hospitals ( 2 Nottingham , 1 Derby ) will provide the interventions , and the University of Nottingham 's Departments of Primary Care , the Division of Rehabilitation and Ageing Unit , and the Trent Institute for Health Service Research will provide the method ological and statistical expertise . Four hundred subjects will be r and omised into the two arms . The primary outcome measure will be the rate of falls over one year . Secondary outcome measures will include the proportion of people experiencing at least one fall , the proportion of people experiencing recurrent falls ( > 1 ) , injuries , fear of falling , quality of life , institutionalisation rates , and use of health services . Cost-effectiveness analyses will be performed to inform health commissioners about re source allocation issues . The importance of this trial is that the results may be applicable to any UK day hospital setting .SitesGeneral practice s across Nottinghamshire and Derbyshire . Day hospitals : Derbyshire Royal Infirmary ( Southern Derbyshire Acute Hospitals NHS Trust)Sherwood Day Service ( Nottingham City Hospital Trust)Leengate Day Hospital ( Queen 's Medical Centre Nottingham University Hospital NHS Trust OBJECTIVE To assess the effectiveness of comprehensive geriatric assessment conducted in day hospitals . DESIGN Retrospective cohort comparison study with restricted inclusion ary criteria and adjustment for baseline characteristics . SETTING A hospital-based geriatric day hospital and geriatric clinic sites ( both in the university and in the community ) . PATIENTS Four hundred sixty-eight patients referred for comprehensive geriatric assessment during a 12-month period . INTERVENTION Comprehensive geriatric assessment in a geriatric day hospital compared with assessment received in clinic sites without a day hospital . MAIN OUTCOME MEASURES Services received in the first 2 weeks ; hospitalization , emergency room visits , placement , death , and change in selected health status measures . Follow-up data was obtained from medical records , a telephone survey , and death certificates . RESULTS Except in the case of rehabilitative services , day hospital patients were more likely to receive interdisciplinary services . The population seen in the day hospital was more functionally impaired and had significantly more dementia and depression . After adjusting for subjects ' baseline characteristics and limiting the analyses to subjects meeting specific inclusion ary criteria , the day hospital had no significant effect on mortality , use of emergency or hospital services , placement , or change on selected measures of health status . For example , compared with the clinic patients , receiving care in the day hospital was associated with an adjusted odds ratio of 1.01 ( 95 % confidence interval : 0.53 , 1.91 ) of being at a higher level of care at 6 months . The results were not sensitive to the choice of inclusion ary criteria . CONCLUSION Given their cost and uncertain effectiveness , day hospitals need additional evaluation before their further diffusion occurs OBJECTIVES To compare the effectiveness of Cooperative Health Care Clinic ( ( CHCC ) group outpatient model for chronically ill , older health maintenance organization ( HMO ) patients ) with usual care . DESIGN Two-year , r and omized , controlled trial conducted with recruitment from February 1995 through July of 1996 . SETTING Nonprofit group model HMO . PARTICIPANTS Two hundred ninety-four adults ( 145 intervention and 149 usual care ) , aged 60 and older ( mean age 74.1 ) with 11 or more outpatient visits in the prior 18 months , one or more self-reported chronic conditions , and expressed interest in participating in a group clinic . INTERVENTION Monthly group meetings held by patients ' primary care physicians . MEASUREMENT Differences in clinic visits , inpatient admissions , emergency room visits , hospital outpatient services , professional services , home health , and skilled nursing facility admissions ; measures of patient satisfaction , quality of life , self-efficacy , and activities of daily living ( ADLs ) . RESULTS Outpatient , pharmacy services , home health , and skilled nursing facility use did not differ between groups , but CHCC patients had fewer hospital admissions ( P=.012 ) , emergency visits ( P=.008 ) , and professional services ( P=.005 ) . CHCC patients ' costs were $ 41.80 per member per month less than those of control patients . CHCC patients reported higher satisfaction with their primary care physician ( P=.022 ) , better quality of life ( P=.002 ) , and greater self-efficacy ( P=.03 ) . Health status and ADLs did not differ between groups . CONCLUSION The CHCC model result ed in fewer hospitalizations and emergency visits , increased patient satisfaction , and self-efficacy , but no effect on outpatient use , health , or functional status OBJECTIVES To compare the effectiveness and costs of a new domiciliary rehabilitation service for elderly stroke patients with geriatric day-hospital care . DESIGN R and omized controlled trial . PARTICIPANTS Stroke patients aged 55 + who required further rehabilitation after hospital discharge or after referral to geriatricians from the community . SETTING Poole area , East Dorset , a mixed urban/rural area on the south coast of Engl and . MAIN OUTCOMES Primary -changes between hospital discharge and 6-month follow-up in physical function as measured by Barthel index . Secondary -changes over this period in Rivermead Mobility Index and mental state ( Philadelphia Geriatric Centre Morale Scale ) and differences in social activity ( Frenchay Activities Index ) and generic health status ( SF-36 ) . Health service and social service cost per patient were compared for the two groups . RESULTS 180 patients were eligible and 140 ( 78 % ) were r and omized . The groups were well balanced for age , sex , social class and initial Barthel index . We achieved follow-up in 88 % of subjects who were alive at 6 months . We detected no significant differences in patient outcomes , although there was a non-significant improvement in measures of physical function and social activity in the domiciliary group . Domiciliary patients had more physiotherapy time per session and more district nurse time , and made greater use of social service day centres and home helps . Total cost per patient did not differ significantly between the two groups , with reduced health service costs in the domiciliary arm offset by higher social service costs . CONCLUSION No significant differences were detected in the effectiveness of the two services . Neither service influenced patients ' mental state , and their social activity remained low . Total costs were similar . A mixed model of day-hospital and domiciliary care may be most cost-effective for community stroke rehabilitation , but this requires further evaluation This study compared the functional ability and perceived health status of stroke patients treated by a domiciliary rehabilitation team or by routine hospital-based services after discharge from hospital . Patients discharged from two acute and three rehabilitation hospitals in Nottingham were r and omly allocated in three strata ( Health Care of the Elderly , General Medical and Stroke Unit ) to receive domiciliary or hospital-based care after discharge . Functional recovery was assessed by the Extended Activities of Daily Living ( ADL ) scale three and six months after discharge and perceived health at six months was measured by the Nottingham Health Profile . A total of 327 eligible patients of 1119 on a register of acute stroke admissions were recruited over 16 months . Overall there were no differences between the groups in their Extended ADL scores at three or six months , or their Nottingham Health Profile scores at six months . In the Stroke Unit stratum , patients treated by the domiciliary team had higher household ( p = 0.02 ) and leisure activity ( p = 0.04 ) scores at six months than those receiving routine care . In the Health Care of the Elderly stratum , death or a move into long-term institutional care at six months occurred less frequently in patients allocated to the routine service , about half of whom attended a geriatric day hospital . Overall there was no difference in the effectiveness of the domiciliary and hospital-based services , although younger stroke unit patients appeared to do better with home therapy while some frail elderly patients might have benefited from day hospital attendance The DOMINO study ( DOMiciliary rehabilitation In NOttingham ) was a r and omized controlled trial comparing domiciliary and hospital-based rehabilitation for stroke patients after discharge from hospital , stratified according to the ward at hospital discharge . The outcomes of these patients have been reported previously . In this paper , we present estimates of health service costs of care . No difference in outcome had been found between the overall services , but we have found the hospital-based costs to be 27 % cheaper . However , different cost-effectiveness patterns are observable when the strata are analysed . Patients from geriatric wards had been shown to be 2.4 times less likely to die or become institutionalized by 6 months if allocated to a day hospital service , although the cost of this service was 25 % more than that of the domiciliary service . Patients from the Stroke Unit who had received domiciliary rehabilitation had been shown to have greater household and leisure abilities at 6 months than those treated in outpatient departments , but the domiciliary service was found to cost 2.6 times more . Patients from general medical wards had similar outcomes whether treated at home or in outpatient departments , but the cost of the latter service was 56 % of the former . Some patients may be best cared for in day hospitals and others may do better if treated at home , but for these groups the clinical advantages are achieved at an expense greater than that incurred by the alternative services . Other patients may do as well if treated in outpatient departments as at home , but the former approach is cheaper . A range of services is required for stroke patients leaving hospital Objective The purpose of this study was to investigate the effects of water exercise at a day service facility and the effects of water exercise frequency on health-related quality of life ( HRQL ) . Methods Participants ( n = 30 ) were r and omly separated into three groups : two indicating exercise frequency , at once-weekly or twice-weekly , and a control group . One-hour exercise intervention sessions were carried out once or twice a week , accordingly , for 24 weeks . The water exercise session comprised a warm-up on l and , activities of daily living ( ADL ) exercises , stretching , strength training , and relaxation in water . HRQL was evaluated using the Medical Outcomes Survey Short-Form 36 ( SF-36 ) question naire , and ADL disability was assessed using the Functional Independence Measure . Results Significant differences were found between pre- and 6 months in both the once- and twice-weekly groups in HRQL ( p < 0.05 ) . No significant difference was found among pre- , 3 months , and 6 months . The effect size between the once and twice groups was moderate in both the physical component summary ( 0.72 ) and mental component summary ( 0.75 ) at 3 months . ADL disability shows significant correlation with HRQL . Conclusion Water exercise intervention at a day service facility improved participants ’ HRQL for 6 months by improving exercise habits and ADL disability . Furthermore , the HRQL change differed according to exercise frequency : twice-weekly exercise showed more rapid improvement than once-weekly Objective : To assess the effect of three weeks of rehabilitation in the home setting for younger patients with stroke with the aim of improving activity level . Design : A r and omized controlled study with blinded evaluations at discharge , three weeks , three months and one year after discharge . Setting : Home of the patient or the ordinary day rehabilitation clinic at the university hospital . Subjects : Fifty-eight patients ( median age 53 years ) consecutively discharged from inpatient rehabilitation with a first occurrence of stroke participated in training directly after discharge . Intervention : Rehabilitation was given for 9 hours/week over three weeks . The home group received individually tailored training , based on the patient 's needs and desires , with a focus on activities in their natural context . Support and information were also given . The intervention in the day clinic group was aim ed mainly at improved functions . Main measures : The main outcome was activity , assessed with the Assessment of Motor and Process Skill ( AMPS ) . The impairment level was also evaluated . Costs were estimated . Result : There were no significant differences between the groups on any of the four assessment s. However , there seemed to be an earlier improvement on some measures ( including AMPS ) for the home group . For both groups there was a greater improvement on the activity level than on the impairment level . The costs of the home group were less than half of the costs of the day clinic group . Conclusion : With the present results , both rehabilitation programmes could be recommended , however , further studies are needed to define patients who may specifically benefit from the home rehabilitation programme . Costs should be taken into consideration This study prospect ively evaluated long-term outcome 2 years after 6 - 8 weeks of day hospital rehabilitation ( DHR ) for stroke in younger patients . Assessment findings after discharge from DHR and at follow-up 2 years later using 3 instruments -- the FIM ( originally known as the Functional Independence Measure ) , SF-36 , and EuroQol ( now known as EQ-5D)--were compared . The study group comprised 50 consecutive patients age 18 - 60 years at the time of their initial stroke who had participated in a prospect i ve study of the effects of DHR after stroke . Living conditions were assessed using the Riks-Stroke stroke care register . Patient h and icaps were grade d according to the Oxford H and icap Scale . The patients maintained functional and cognitive capacity , as well as self-rated health and health-related quality of life ( HRQoL ) , 2 years after discharge . A significant improvement was also seen in cognitive capacity and in HRQoL as assessed by EuroQol , but in only 1 of the 8 SF-36 domains . The changes in functional capacity and HRQoL were significantly and inversely correlated with the scores at discharge from DHR . Follow-up scores for EuroQol were correlated with scores for physical and cognitive capacity . Women demonstrated less improvement in EuroQol scores than men . Our findings indicate that most stroke patients who sustained initial acute stroke at age 18 - 60 years and received 6 - 8 weeks of DHR poststroke maintained functional and cognitive capacity as well as HRQoL after 2 years . Some patients even may have improved their cognitive capacity and Two long-term care setting s not now covered by Medicare — adult day care and homemaker services — were studied in a r and omized experiment to test the effects on patient outcomes and costs of using these new services . This article reports findings for day care . Patients ’ physical , psychosocial and health functions were assessed quarterly , and their Medicare bill files were obtained . Medicaid data were obtained on most patients , but few used many Medicaidcovered long-term care services . Multistage analysis was performed to mitigate effects of departures from the r and omized design . Day-care patients showed no benefits in physical functioning ability at the end of the study , compared with the control group . Institutionalization in skilled nursing facilities was lower for the experimental group than the control group , but factors other than the treatment variable appeared to explain most of the variance . There was a possibility that life was extended for some day-care patients . The new services averaged $ 52 per day or $ 3,235 per year . When costs for existing Medicare services used were added , the yearly cost of the experimental group was $ 6,501 , compared with $ 3,809 for the control group — an increase of $ 2,692 or 71 per cent Objective : To compare day hospital to day centre rehabilitation using scales to measure mobility , activities of daily living and quality of life . Design : Single blind r and omized controlled trial with home assessment s at baseline ( twice ) , six weeks and three months . Setting : Mainly rural health district . Day hospital and social services day centres in market towns . Interventions : Day hospital treatment or day centre rehabilitation by a physiotherapist and two health support workers . Main outcome measures : World Health Organization mobility scale scored with and without aid , Nottingham Extended Activities of Daily Living Scale and Nottingham Health Profile . Subjects : One hundred and five physically disabled older patients living at home referred for day hospital rehabilitation or maintenance before discharge from hospital ( 66 ) or referred as out patients ( 39 ) . Results : At three months there were no statistically significant differences between rehabilitation at day hospital and day centre for any of the outcome measurements . However , there were significant improvements between baseline and three months for the following subscales [ mean change per six-week period ( 95 % confidence interval ) ] : WHO mobility subscale ( with aid ) – 0.67 ( –0.99,–0.35 ) ; Nottingham Health Profile mobility subscale –10 ( –15.5,–4.5 ) Nottingham extended ADL mobility subscale + 3.08 ( 1.78,4.37 ) ; Nottingham extended ADL leisure subscale + 1.66 ( 0.96,2.36 ) . Conclusion : There were no differences between day hospital and day centre in the outcomes measured . Day rehabilitation appeared to improve functional ability and mobility and scales reflecting these domains deserve further evaluation as outcome measures in this patient group . However , no improvement in quality of life was observed OBJECTIVE To determine if mobility and functional status of patients attending a geriatric day hospital are maintained three months after discharge . DESIGN Prospect i ve , before-after , quasi-experimental design . PARTICIPANTS Community-dwelling elderly referred for comprehensive geriatric assessment and multidisciplinary management . METHODS All patients who attended a geriatric day hospital for at least 5 visits and discharged between 1 August , 1999 and 1 March , 2000 were eligible ( n = 41 ) . Measurements were performed at admission , discharge and three months post-discharge . Data were analyzed using one way repeated measures ANOVA for parametric data and the Friedman-Chi square test for non-parametric data . OUTCOME MEASURES Barthel Index , Timed Up and Go Test , Berg Balance Scale , Mini-Mental Status Examination , Geriatric Depression Scale . RESULTS From admission to discharge , significant improvements were seen in Timed Up and Go Test , Berg Balance Scale , and Geriatric Depression Scale ( all P < or=0.002 ) . From discharge to 3 months post-discharge , the Timed Up and Go Test , Berg Balance Scale and Mini-Mental Status Examination declined ( all P<0.001 ) with no significant change in Barthel Index or Geriatric Depression Scale . From admission to 3 months post-discharge , Mini-Mental Status Examination scores declined ( p=0.002 ) and Geriatric Depression Scale scores improved ( p=0.007 ) , with all other outcomes unchanged . CONCLUSION No sustained improvements in mobility or functional status were seen at 3 months following discharge from a geriatric day hospital . Further studies exploring methods to delay progressive deterioration in multiple domains are necessary OBJECTIVE To study the effectiveness of rehabilitative and medically oriented day hospital care on community-based long-term care patients . DESIGN A r and omized , controlled trial . SETTING AND PARTICIPANTS 177 patients on home-care in a rural area were r and omized into two groups . Patients in one group were offered a 2-month period of rehabilitation and medical care in a recently opened day hospital , and in the other group patients were offered treatment , as before , in home care . Both groups were examined at the beginning and at 2 , 5 and 12 months . INTERVENTION Rehabilitative and medically oriented day hospital care . OUTCOME MEASURES Use of health services , physical functioning measured by the Katz ADL Index , subjective health , symptoms , and satisfaction with care . RESULTS The groups used hospitals ( excluding the day hospital treatment ) equally during the follow-up year . The treatment group had significantly more specialist consultations than did the control group . There were no clinical ly significant differences in the changes in the Katz ADL Index although more changes were found in the treatment group . The number of symptoms was reduced significantly in the treatment group , whereas the number of symptoms remained unchanged in the control group . The patients ' views of their own health improved in the treatment group . CONCLUSION Day hospital care affects the quality of life of older people , but it does not reduce the use of other health services , nor does it clinical ly significantly improve the physical functioning of older people Objective : To assess the efficacy of a programme of continuing self-directed exercises for people discharged home after a stroke , supervised once a week by therapists . Design : A r and omized controlled trial of 100 patients discharged from hospital after a stroke , requiring ongoing therapy . The control group received outpatient or day hospital therapy ; the experimental group were visited once a week by an occupational and /or physiotherapist who prescribed a programme of exercises and activities for the following week . Subjects were studied for the first three months after discharge from hospital . Setting : A district general hospital , or the homes of subjects r and omized to the experimental group , in New Zeal and . Main outcome measures : ( 1 ) Characteristics of the groups , ( 2 ) gait speed , limb function , activities of daily living , ( 3 ) time with therapists , ( 4 ) mood of both subjects and caregivers , ( 5 ) anticipation of outcome at entry , compared with perceived outcome at exit . Results : No statistical differences between the control and experimental groups in characteristics , or in any outcomes measured , except that the contact time period , but not the number of visits , was longer in the experimental group ( p = 0.003 ) . Conclusions : A supervised home-based programme is as effective as outpatient or day hospital therapy The aim of this study was to evaluate the effects of geriatric day care on patients and caregivers . Day care patients ( n = 43 ) were compared with an untreated matched control group ( n = 40 ) . Matching criteria were age , gender , physical and mental health status , and socioeconomic status . The mean age of both groups was 79.5 years . Data were collected at three measurement points : T1 took place during the first 10 days of service use , T2 was conducted 6 months later , and T3 took place 9 months after service use began . In addition , a short follow-up was conducted 6 months after T3 . Well-being , dementia symptoms , health indicators , and activities of daily living were investigated . Individual growth curves of these patient variables were computed and analyzed with multivariate analyses of variance . The results show significant positive effects of day care on well-being and dementia symptoms . Patients in day care stabilized or improved on various measures , whereas the untreated control participants worsened . Follow-up data showed a significant decline in health in the control group in comparison with the day care users . Results concerning effects on caregivers were not that clear . Individual change parameters in subjective well-being and burden did not differ between the two groups of caregivers in the longitudinal follow-up . In a semistructured interview , however , caregivers of patients in the treatment group reported substantial positive change due to use of day care The DOMINO study compared domiciliary and hospital-based rehabilitation services for stroke patients after discharge from hospital , stratified by the hospital ward at discharge . No difference between the services had been found at 6 months , but home therapy was better than outpatient department therapy at improving household ability and leisure activity in the patients discharged from the Stroke Unit ( SU ) , and attendance at a day hospital may have been better than a domiciliary service at preventing death or institutionalization for patients discharged from Health Care of the Elderly ( HCE ) wards . We report the follow-up of the patients between 6 months and 1 year after discharge , during which time few patients received further treatment and little change in health or function occurred . Over this period the benefits of domiciliary rehabilitation in the SU group were lost , largely because the patients who had been treated in outpatient departments continued to improve . Between 6 months and 1 year the numbers of HCE patients in the two treatment groups who died or were institutionalized were similar , but the advantage of day hospital attendance was still evident at 1 year BACKGROUND AND PURPOSE Much controversy exists over the value of geriatric day hospitals in the rehabilitation of elderly patients , and cerebrovascular accident is a particularly common diagnosis among patients referred to these day hospitals . We carried out a prospect i ve , r and omized study to compare the outcomes of elderly stroke patients managed by a geriatric team using a day hospital facility versus conventional medical management . METHODS One hundred twenty elderly patients with acute stroke were r and omized to inpatient care on a stroke ward under the care of either a neurologist or a geriatric team . Those under the care of neurologists were hospitalized until the attending physician felt that the patients had reached full rehabilitation potential . Patients under the care of the geriatric team were discharged home as soon as the team felt they were able to cope and given follow-up rehabilitation at the day hospital . Family or community support was arranged when necessary for both treatment groups . On recruitment , patient demographics , medical history , clinical features related to stroke , and functional ability as measured by the Barthel Index were noted . Subjects were review ed at 3 and 6 months to assess functional level , hospital and outpatient services received , general well-being , mood , and level of satisfaction . Costs of treatment of the two groups were also compared . RESULTS Functional improvement ( Barthel Index score ) was greater in the group managed by the geriatricians with a day hospital facility compared with the conventional group at 3 months ( P = .03 ) . There were also fewer outpatient visits among the day hospital patients at 6 months ( P = .03 ) . No significant difference was found in costs between the two treatment groups . CONCLUSIONS Compared with conventional medical management , care in the geriatric day hospital hastened functional recovery and reduced outpatient visits in elderly stroke patients without additional cost Objective : To determine whether a programme of multidisciplinary rehabilitation and group support achieves sustained benefit for people with Parkinson ’s disease or their carers . Methods : The study was a r and omised controlled crossover trial comparing patients and carers who had received rehabilitation four months before assessment with those who had not . Patients were recruited from a neurology clinic , attended a day hospital from home weekly for six weeks using private car or hospital transport , and received group educational activities and individual rehabilitation from a multidisciplinary team . Patients were assessed at entry and at six months using a 25 item self assessment Parkinson ’s disease disability question naire , Euroqol-5d , SF-36 , PDQ-39 , hospital anxiety and depression scale , and timed st and -walk-sit test . Carers were assessed using the carer strain index and Euroqol-5d . Results : 144 people with Parkinson ’s disease without severe cognitive losses and able to travel to hospital were registered ( seven were duplicate registration s ) ; 94 had assessment s at baseline and six months . Repeated measures analysis of variance comparing patients at the 24 week crossover point showed that those receiving rehabilitation had a trend towards better st and -walk-sit score ( p = 0.093 ) and worse general and mental health ( p = 0.002 , p = 0.019 ) . Carers of treated patients had a trend towards more strain ( p = 0.086 ) . Analysis comparing patients before and six months after treatment showed worsening in disability , quality of life , and carer strain . Conclusions : Patients with Parkinson ’s disease decline significantly over six months , but a short spell of multidisciplinary rehabilitation may improve mobility . Follow up treatments may be needed to maintain any benefit OBJECTIVE --Comparison of day hospital attendance and home physiotherapy for stroke patients leaving hospital to determine which service produces greater functional and social improvement for the patient , reduces emotional stress for the care giver , and lessens the need for community support . DESIGN --Stratified , r and omised trial of stroke patients attending day hospital two days a week or receiving home treatment from a community physiotherapist . The six month assessment results are reported in this paper . SUBJECTS-- Patients over 60 years old resident within the Bradford metropolitan district discharged home after a new stroke with residual disability . SETTING --Four day hospitals in two health authorities and domiciliary work undertaken by experienced community physiotherapists . MAIN OUTCOME MEASURES --Barthel index , functional ambulatory categories , Motor Club assessment , Frenchay activities index , and Nottingham health profile were used . Carers ' stress was indicated by the general health question naire . Treatment given and community care provided were recorded . RESULTS --Of 124 patients recruited , 108 were available for re assessment at six months . Both treatment groups had significantly improved in functional abilities between discharge and six months . The improvements were significantly greater for patients treated at home ( Mann-Whitney test ; Barthel index , median difference 2 ( 95 % confidence interval 0 to 3 ) p = 0.01 ; Motor Club assessment , median difference 2 ( 1 to 5 ) , p = 0.01 ) . The home treated patients received less treatment ( median difference 16 ( 11 to 21 ) treatments , p less than 0.001 ) . More than a third of patients in both groups showed depressed mood , and a quarter of care givers were emotionally distressed . CONCLUSIONS --Home physiotherapy seems to be slightly more effective and more re source efficient than day hospital attendance and should be the preferred rehabilitation method for aftercare of stroke patients . New strategies are needed to address psychosocial function for both patients and care givers Collaborative working in care for older people is often seen as a desirable goal . However , there can be problems with this approach . This paper reports on a single blind r and omized controlled trial which was carried out to compare outcomes of rehabilitation in two setting s : a day hospital and social services day centres augmented by visiting therapists . The subjects were 105 older patients . Principal outcome measures were the Barthel Index , Philadelphia Geriatric Centre Morale Scale and the Caregiver Strain Index . Two aspects of the trial are examined here . Firstly , we investigated whether trial patients were more disabled than regular day centre attendees . Levels of health and well being amongst trial patients were compared with those of a r and om sample of 20 regular attendees from both of the participating day centres and an additional voluntary sector day centre . Secondly , key staff from the different setting s were interviewed to assess how well the day centre model had worked in practice . Trial patients were significantly more disabled than regular day centre attendees according to the Barthel Index ( P < 0.001 ) , but this difference was no longer significant after three months of treatment . The day centre model had several problems , principally discharge policy , acceptability , facilities and attitudes of staff and regular attendees . Positive aspects of the day centre model , as well as successful rehabilitation , included shared skills , knowledge and re sources . This paper suggests that collaborative working in day centres requires multi purpose facilities . If health staff maintain a permanent presence , benefits can include improved joint working , easier access to health care and the use of rehabilitative therapy as a preventative strategy . Day care setting s can be analyzed as representing different types of communities . Allowing older users a greater degree of choice in facilities may increase the acceptability of care Objective : To compare the outcome of day hospital to day centre rehabilitation . Design : Single blind r and omized controlled trial with home assessment s at baseline ( twice ) , six weeks and three months . Setting : Mainly rural health district . Day hospital and social services day centres in market towns . Subjects : One hundred and five physically disabled older patients living at home referred for day hospital rehabilitation or maintenance before discharge from hospital ( 66 ) or referred as out patients ( 39 ) . Interventions : Day hospital treatment or day centre rehabilitation by a physiotherapist and two health support workers . Main outcome measures : Barthel Index , Philadelphia Geriatric Morale Scale and Caregiver Strain Index . Results : More day centre ( 23/55 ) than day hospital patients ( 6/50 ) ( p < 0.001 ) withdrew from allocated treatment by choice or because of operational difficulties . Both groups improved significantly in functional ability and reduction of care-giver strain by three months but there was no significant difference between groups . The mean improvement in Barthel Index ( st and ard error ) for day hospital = + 1.5 ( 0.41 ) ( n = 34 ) and day centres = + 1.5 ( 0.48 ) ( n = 38 ) . The mean difference ( 95 % confidence interval ) between day hospital and day centre was 0 ( –1.28 , + 1.28 ) . Likewise the mean Philadelphia Geriatric Morale Scale improvement for day hospital + 1.8 ( 0.66 ) ( n = 35 ) and day centres was + 0.9 ( 0.63 ) ( n = 38 ) . The mean difference was –0.88 ( –2.7 , + 0.95 ) . The mean reduction in Caregiver Strain for day hospital was –1.45 ( 0.5 ) ( n = 23 ) and day centre was –1.59 ( 0.47 ) ( n = 27 ) . The difference was –0.14 ( 1.52,+1.24 ) . ( These analyses are all on an intention-to-treat basis . ) Conclusion : Whilst the improvement in functional ability and care-giver strain was similar in both groups , day centre rehabilitation was less popular and had practical difficulties . If these difficulties can be overcome the model should be tested elsewhere This paper describes how a prospect i ve evaluation of the costs and effectiveness of day hospital care for the elderly and its alternatives could be undertaken . The number of day hospitals for the elderly has grown from zero to slightly over 300 in just over 20 years . Despite this there is no study in the existing literature which gives an indication of whether day hospitals provide a reasonable return on this substantial investment . The best way of determining whether day hospitals are a better investment than alternative modes of care would be a r and omized controlled trial involving comparison of subgroups of day hospital patients against similar subgroups utilizing alternative modes of care , the costing of each patient 's consumption of services within the treatment mode in which they commence the study plus any subsequent use of other services over a predetermined time period , the collection of clinical , social and psychological outcome data ( including data on dependency ) for each subgroup before , during and at the end of the study period , and some measure of patients ' and relatives ' satisfaction with the treatment received Objectives : To assess outcomes and satisfaction among frail elderly day care clients and their informal caregivers and the impact of adult day care on the cost of health services . Methods : One-hundred eight elderly participants were r and omly assigned to the experimental group ( immediate admission to an adult day care center ) and 104 participants to the control group ( 3 months on a waiting list ) . Results : Participants ’ and caregivers ’ subjective perceptions of the day center ’s effects were positive . However , using st and ard research instruments , there was no evidence of an effect of day center attendance on the client ’s anxiety , depression , or functional status ; on caregiver burden ; or on the cost of health services . Discussion : It is difficult to demonstrate objective ly the benefits of programs and interventions that are perceived by clients , caregivers , and staff to have positive effects . In future studies , maintenance of high levels of participation should be incorporated as an explicit program goal The financial cost of stroke rehabilitation is considerable but few cost-effectiveness studies are available to guide clinical practice . The Bradford community stroke trial was a r and omised trial comparing day hospital attendance with home physiotherapy for elderly stroke patients leaving hospital . The outcome measurements used indicated a consistent modest advantage in favour of home physiotherapy . This advantage is now re-examined in conjunction with the quantified costs of the rehabilitation services and community support received by the two patient groups . The results show that the median cost for the day hospital patients over the first eight weeks was 620.00 pounds ( interquartile range 555.00 - 730.00 pounds ) and 385.00 pounds for the home physiotherapy group ( interquartile range 240.00 - 510.00 pounds ) . These costs were significantly different ( median difference 265.00 pounds , 95 % confidence interval 190.00 - 340.00 pounds ; p < 0.01 ) . There were no significant differences between the two groups for the indirect costs . This cost-effectiveness study supports the clinical trial result that home physiotherapy should be the treatment of choice for stroke aftercare BACKGROUND Older adults who receive training for functional skills in context ually appropriate environments may show greater functional improvement than persons trained in a traditional environment . Functionally limited older adults receiving training in context ually appropriate environments ( simulated home and community setting s ) may show greater improvement in activities of daily living ( ADL ) than persons trained in a traditional manner . METHODS Eighty-eight patients from a day hospital , aged 65 years or older , were r and omized to either receive rehabilitation in a simulated environment ( Easy Street ) or in a gymnasium setting . Rehabilitation focused on retraining functional skills in a context ually appropriate environment ( Easy Street ) or in a traditional setting ( gymnasium ) using motor learning principles for a period of 16 weeks . Outcome measures included the Structured Assessment of Instrumental Living Skills ( SAILS ) , a performance measure with criterion and timed components ; a self-report health status question naire , the Short Form-36 ( SF-36 ) ; and the patient-orientated goal -directed Canadian Occupational Performance Measure ( COPM ) . RESULTS There were no group differences on any of the outcome measures : SAILS ( p = .3 ) ; the SF-36 physical ( p = .83 ) and mental ( p = .51 ) ; and the COPM performance scale ( p = .94 ) and satisfaction scale ( p = .40 ) . CONCLUSIONS Although we have not excluded benefits of context ually appropriate rehabilitation environments with different intervention approaches , at different stages of rehabilitation or with patients at higher functional levels , our results suggest the appropriateness of a moratorium on these expensive interventions pending demonstration of clear positive effects determined from further study BACKGROUND Effective new strategies that complement primary care are needed to reduce disability risks and improve self-management of chronic illness in frail older people living in the community . OBJECTIVE To evaluate the impact of a 1-year , senior center-based chronic illness self-management and disability prevention program on health , functioning , and healthcare utilization in frail older adults . DESIGN A r and omized controlled trial . SETTING A large senior center located in a northeast Seattle suburb . The trial was conducted in collaboration with primary care providers of two large managed care organizations . PARTICIPANTS A total of 201 chronically ill older adults seniors aged 70 and older recruited through medical practice s. INTERVENTION A targeted , multi-component disability prevention and disease self-management program led by a geriatric nurse practitioner ( GNP ) . MEASUREMENTS Self-reported Physical function , physical performance tests , health care utilization , and health behaviors . RESULTS Each of 101 intervention participants met with the GNP from 1 to 8 times ( median = 3 ) during the study year . The intervention group showed less decline in function , as measured by disability days and lower scores on the Health Assessment Question naire . Other measures of function , including the SF-36 and a battery of physical performance tests , did not change with the intervention . The number of hospitalized participants increased by 69 % among the controls and decreased by 38 % in the intervention group ( P = .083 ) . The total number of inpatient hospital days during the study year was significantly less in the intervention group compared with controls ( total days = 33 vs 116 , P = .049 ) . The intervention led to significantly higher levels of physical activity and senior center participation and significant reductions in the use of psychoactive medications . CONCLUSIONS This project provides evidence that a community-based collaboration with primary care providers can improve function and reduce inpatient utilization in chronically ill older adults . Linking organized medical care with complementary community-based interventions may be a promising direction for research and practice |
12,993 | 20,556,778 | Topical diclofenac , ibuprofen , ketoprofen , and piroxicam were of similar efficacy , but indomethacin and benzydamine were not significantly better than placebo .
Local skin reactions were generally mild and transient , and did not differ from placebo .
There were very few systemic adverse events or withdrawals due to adverse events .
Topical NSAIDs can provide good levels of pain relief , without the systemic adverse events associated with oral NSAIDs , when used to treat acute musculoskeletal conditions | BACKGROUND Use of topical NSAIDs to treat acute musculoskeletal conditions is widely accepted in some parts of the world , but not in others .
Their main attraction is their potential to provide pain relief without associated systemic adverse events .
OBJECTIVES To review the evidence from r and omised , double-blind , controlled trials on the efficacy and safety of topically applied NSAIDs in acute pain . | One hundred patients who presented to the accident and emergency ( A&E ) department with an acute ankle sprain were entered into a study to determine the efficacy of topical ibuprofen cream by using a double-blind placebo controlled design in a single type of soft-tissue injury . The subjects were given either topical ibuprofen cream or a placebo cream in addition to the st and ard management of the department . Patients kept diaries recording walking ability and pain visual analogue scales for resting , st and ing and walking . A total of 51 patients returned diaries that were suitable for analysis . Patients using the topical ibuprofen cream had significant reduction in pain scores over the first 48 h of treatment 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 A double-blind , placebo-controlled , multi-centre study was carried out to assess the efficacy and tolerability of percutaneous niflumic acid gel in the treatment of uncomplicated ankle sprains . Sixty patients were enrolled in three centres and were r and omly allocated to receive treatment with 2.5 % percutaneous niflumic acid gel or placebo gel applied 3-times daily for 7 days . Clinical evaluations were made on entry to the study , after 3 days and at the end of treatment . The major efficacy criteria were the pain felt by the patient and the investigators ' and patients ' global evaluation of effectiveness of the treatment . Adverse events that occurred were also noted . The results showed that topically applied 2.5 % niflumic acid gel was superior to placebo in the treatment of ankle sprains in respect of all major parameters studied . Niflumic acid gel and the placebo were shown to be equally well tolerated . The study findings indicate that treatment with topical niflumic acid gel is effective in treating uncomplicated ankle sprains and results in improved clinical signs on Day 4 and after 7 days Topical anti-inflammatory management of superficial and deep phlebopathy with feprazone and benzidamine was compared in a double-blind test . Both drugs were active and well tolerated . Significantly less time was needed to obtain a cure with feprazone Objectives : To investigate the clinical efficacy and safety of a newly developed diclofenac patch in the topical treatment of blunt impact injuries . Methods : This was a r and omised , placebo controlled , double blind , multicentre study in 120 patients with traumatic blunt soft tissue injury . Within 3 h of the injury participants of sport competitions and training camps were enrolled and treated twice daily with the diclofenac or a placebo patch over a period of 7 days . Patients were r and omised ( 1:1 ) to two parallel groups . Tenderness produced by pressure was measured twice daily during the first 3 days after enrolment as well as at day 7 . Tenderness was defined as the amount of pressure ( measured by a calibrated caliper at the centre of the injury ) that first produced a pain reaction as reported by the patient . Results : The primary efficacy variable was the area under the curve for tenderness over the first 3 days . The diclofenac patch was significantly more effective than placebo ( p<0.0001 ) . The treatment effect was 64.7 kp h/cm2 ( 95 % confidence interval 48.7 to 80.9 ) between diclofenac and placebo patches . These results were supported by all secondary efficacy variables . The diclofenac patch produced rapid pain relief as reflected by the time to reach resolution of pain at the injured site which was significantly shorter compared to placebo ( p<0.0001 ) . The diclofenac patch was well tolerated . The most frequently observed adverse events were local cutaneous adverse reactions ( pruritus , rash ) of minor severity occurring with the same frequency as in the placebo group . Conclusions : A newly developed diclofenac patch is effective and safe for the treatment of blunt impact injuries Introduction Gastrointestinal upset and local pain commonly limit the use of oral nonsteroidal anti-inflammatory drugs and corticosteroid injection as treatments for lateral epicondylitis . Transdermal administration of an anti-inflammatory drug could avoid these adverse effects . Purpose To determine the effectiveness of topical diclofenac as a treatment of lateral epicondylitis . Methods A convenience sample of 14 subjects meeting clinical criteria of chronic lateral epicondylitis participated in this r and omized , double blind , crossover study . Each subject applied a plutonic lecithin liposomal organo-gel ( PLO ) over the affected lateral elbow three times daily for 1 week , followed by a 1-week “ washout ” period of no gel . A second topical PLO gel was then applied similarly for 1 week . Both gels were identical , but only one gel contained 2 % diclofenac . Treatment order was r and omized , and both the subject and tester were blinded . Pain and isometric wrist extension strength were measured using a visual analog pain scale ( VAS ) and a mounted manual muscle testing dynamometer , respectively , at the following time periods : just before application of the first gel , the last day of using the first gel , the last day of the washout week , and the last day of using the second gel . Analysis was performed using repeated measures analysis of variance . Results When subjects used diclofenac PLO , pain was significantly less than that during the pretreatment , washout , and placebo PLO periods ( mean VAS ; diclofenac PLO , 2.1 ; pretreatment , 3.5 ; washout , 3.4 ; placebo PLO , 3.6 ) . Average wrist extension strength was significantly greater when subjects used diclofenac PLO ( 8.4 kg ) than it was before treatment ( 5.9 kg ) . One subject developed a local rash while using diclofenac PLO . Conclusion Topical 2 % diclofenac in PLO appears to provide effective short-term reduction in elbow pain and wrist extensor weakness associated with chronic lateral epicondylitis A double-blind study vs placebo was carried out on 82 pts suffering from soft tissue trauma , to evaluate the efficacy and tolerance of a new anti-inflammatory , non-steroidal analgesic for topical use , 3 % BPAA . Clinical results obtained by the group treated with BPAA gel were highly significant ( p = 0.01 ) and positive , showing absence of local and systemic side-effects . Accordingly , BPAA gel can be recommended for treatment of soft tissue trauma One hundred and thirty-one male and female out patients , aged 18 - 70 yr , with acute pain in the ankle joint caused by a post-traumatic sprain , entered a multicentre , r and omised , double-blind , parallel-group , study . The patients were assigned to a 40 mg flurbiprofen patch ( n = 65 ) or a non-medicated ( but otherwise identical ) control ( n = 66 ) , 12-hourly over 7 days , and were assessed at entry and after 3 and 7 days treatment . On day 7 , spontaneous pain ( the prime efficacy parameter ) , as evaluated by the patient on a visual analogue scale in the physician 's office , showed significant improvement in the 40 mg flurbiprofen patch group compared to control ( change from baseline ) ( p = 0.039 ) , a result corroborated by the evaluation of the periarticular oedema : a reduction of 77.4 % was observed in the 40 mg flurbiprofen patch group , compared with 63.8 % in the control group ( p = 0.025 ) . The other selected efficacy criteria showed changes with a trend in favour of the 40 mg flurbiprofen patch but without statistical significance . Two mild and local adverse events were reported by two flurbiprofen patch patients , but neither patients discontinued the treatment prematurely . Physicians and patients found the flurbiprofen patch to be efficacious and well tolerated . Compliance was excellent in both groups . The efficacy and tolerability of the 40 mg flurbiprofen patch are therefore confirmed in the treatment of acute ankle sprains Abstract Objective : To determine whether inappropriate subgroup analysis together with chance could change the conclusion of a systematic review of several r and omised trials of an ineffective treatment . Design : 44 r and omised controlled trials of DICE therapy for stroke were performed ( simulated by rolling different coloured dice ; two trials per investigator ) . Each roll of the dice yielded the outcome ( death or survival ) for that “ patient . ” Publication bias was also simulated . The results were combined in a systematic review . Setting : Edinburgh . Main outcome measure — Mortality . Results : The “ hypothesis generating ” trial suggested that DICE therapy provided complete protection against death from acute stroke . However , analysis of all the trials suggested a reduction of only 11 % ( SD 11 ) in the odds of death . A predefined subgroup analysis by colour of dice suggested that red dice therapy increased the odds by 9 % ( 22 ) . If the analysis excluded red dice trials and those of poor method ological quality the odds decreased by 22 % ( 13 , 2P=0.09 ) . Analysis of “ published ” trials showed a decrease of 23 % ( 13 , 2P=0.07 ) while analysis of only those in which the trialist had become familiar with the intervention showed a decrease of 39 % ( 17 , 2P=0.02 ) . Conclusion : The early benefits of DICE therapy were not confirmed by subsequent trials . A plausible ( but inappropriate ) subset analysis of the effects of treatment led to the qualitatively different conclusion that DICE therapy reduced mortality , whereas in truth it was ineffective . Chance influences the outcome of clinical trials and systematic review s of trials much more than many investigators realise , and its effects may lead to incorrect conclusions about the benefits of treatment Anecdotally many athletes use non-steroidal anti-inflammatory gels during competition to allow continued participation . To determine if this clinical practice is useful a r and omised placebo-controlled study was conducted at the 5-day 2004 Red Cross Murray River Marathon . Forty-two kayakers presented with wrist extensor tenosynovitis while competing in the single and double kayak events . All subjects received st and ard treatment of ice , stretches and massage for wrist tenosynovitis before being r and omised into a placebo or 1 % diclofenac gel group . Evaluation was done by using a visual analogue scale ( 0 - 10 ) for pain and by clinical grading ( 0 - 3 ) . The main outcome measurements were reduction in pain and clinical grading , the requirement for a rescue medication ( paracetamol or diclofenac tablets ) and effect on performance times . Both groups had similar pain scores and clinical grading on the first and fifth days of pain . On the second to fourth days of pain there was clearly no benefit and possibly a detrimental effect on pain with diclofenac gel relative to placebo . However , diclofenac tablets were possibly beneficial for pain relative to paracetamol tablets . The effects of pain and the various treatments on performance time were either trivial ( < 0.5 % ) or small , but none was particularly clear . We conclude that st and ard treatment appears to be sufficient for the management of wrist extensor tenosynovitis during competition To evaluate the efficacy and tolerability of the new diclofenac-N-(2-hydroxyethyl)-pyrrolidine lecithin gel ( DHEP lecithin gel , with 1.3 % DHEP and 2.4 % lecithin ) compared with the efficacy and tolerability of diclofenac-N-(2-hydroxyethyl)-pyrrolidine gel ( DHEP gel ) in peri and extraarticular inflammatory states , a controlled , r and omized , double-blind clinical study was conducted . Two groups of 50 patients each were enrolled and were given one of the two different formulations with a slight massage on the painful area three times a day for 10 consecutive days . Patients received a self-evaluation notebook in which to record daily assessment of spontaneous pain ( Huskisson 's visual analogue scale ) . On days 0 , 3 and 10 , the patients were visited by the investigator . All patients completed the study . The assessment of spontaneous pain showed that although pain decreased in both groups , the decrease was more marked in patients taking DEHP lecithin gel and that it reached a statistically significant difference at days 5 , 6 , 7 and 8 . This decrease was also confirmed by assessment s on the ordinal scale . Although periarticular swelling disappeared in both groups , swelling severity decreased sooner in patients taking DHEP lecithin gel . The efficacy and safety of both treatments was judged to be good or excellent by 70 % of the patients in each group . The efficacy of the active principle , pyrrolidine salt , is confirmed . Moreover , the formulation containing lecithin passes through the skin lipid barrier more easily than the formulation without lecithin and is as valid as the other in the therapy of rheumatic disorders . Finally , DHEP lecithin gel preparation has a quicker therapeutic action on symptoms , such as spontaneous pain and local swelling , than DHEP gel Fentiazac 5 % cream was applied topically on limited articular and extraarticular inflammatory lesions in the course of a double-blind clinical trial versus placebo . The drug proved to be satisfactorily tolerated and also therapeutically effective since it changed significantly ( p < 0.05 — < 0.01 ) the spontaneous course of the microtraumatic pathologic pattern producing an early attenuation and resolution of the painful and functional symptomatic pattern Two hundred and thirty-one patients with acute soft tissue injuries were treated in a double-blind placebo-controlled study of felbinac ( biphenylacetic acid ) gel applied three times daily to the injured site . Those treated with felbinac had significantly greater improvement at Day 4 ( p less than 0.001 ) and Day 7 ( p less than 0.02 ) than those who received placebo . Patients ' self- assessment diary cards confirmed superiority of the active treatment as early as Day 2 of the study . Local skin reactions were few ( three per cent ) , mild and recovered spontaneously . Felbinac is an effective management for acute soft tissue injuries and because of its topical application may be safer than oral non-steroidal anti-inflammatory drugs for the treatment of these conditions In a double-blind , placebo-controlled study the efficacy and safety of topical ketorolac tromethamine were assessed in the reduction of inflammation and pain due to ankle sprain . Ketorolac 2 % gel was compared with etofenamate and placebo ( ketorolac vehicle ) in a 15-day study . Patients attended for visits on days 1 ( admission ) , 2 , 3 , 4 , 8 , and 15 of the study . Measurements of efficacy were ankle volume , pain measured on visual analogue scales ( VAS ) and verbal rating of pain . Safety was assessed by volunteered adverse events and vital signs . A total of 37 patients was admitted to the study of whom 13 received ketorolac , 12 placebo , and 12 etofenamate . One patient receiving ketorolac was lost to follow-up on day 15 owing to an unrelated accident . The remaining 36 patients completed the study . Ketorolac was significantly better than placebo in reducing the volume of the injured ankle based on the maximum , the area under the curve , and the day 15 percentage changes in ankle volume . Results for etofenamate were similar to those for ketorolac for all three variables and there were no significant differences between the active treatments . Reductions in VAS pain at rest were more marked in the ketorolac group than either of the other groups at all visits . On day 4 the differences between ketorolac and each of the other groups were statistically significant . Reductions in VAS pain on movement were also greatest for the ketorolac group at all visits . The differences between ketorolac and each of the other groups achieved statistical significance on days 4 and 8 , but were marginal in terms of significance on day 2 . ( ABSTRACT TRUNCATED AT 250 WORDS To evaluate the efficacy of the new diclofenac-N-(2-hydroxyethyl)-pyrrolidine gel formulated with lecithin ( DHEP lecithin ) compared with diclofenac-N-(2-hydroxyethyl)-pyrrolidine gel ( DHEP gel ) without lecithin in mild-to-moderate posttraumatic injuries ( grade 1 ankle , knee and muscle injuries ) , a multicenter , double-blind , controlled study was carried out . A total of 100 patients were enrolled and r and omly assigned to either DHEP lecithin ( n = 52 ) or DHEP gel ( n = 48 ) treatment . All patients concluded the treatment period except for five , who did not turn up to their respective investigational sites for the follow-up visits . According to an intention-to-treat approach , they were all included in the statistical analysis . As for the efficacy and safety analysis , the primary variable was " pain on movement " as measured by a Huskisson visual analog scale . During the first 3 days of treatment each group recorded a significant within-group decrease , but patients treated with DHEP lecithin showed a decrease in absolute value that was statistically greater than that obtained with DHEP gel ( p = 0.025 ) . At the end of the treatment period ( day 10 ) the difference between groups was still statistically significant ( p = 0.036 ) . The statistical analysis of the secondary efficacy variables showed significant results in favor of DHEP lecithin treatment . These were superimposable on the results found for the primary variable . The global efficacy and tolerability judgments , reported either by patient or by physician , showed no statistical difference between treatment groups . Due to the presence of lecithin in the new gel formulation , DHEP lecithin showed a faster and significantly more marked therapeutic effect compared with that of DHEP gel Background Topical nonsteroidal anti-inflammatory drugs offer the advantage of enhanced drug delivery to local affected tissues with low plasma levels and an expected reduced incidence of systemic adverse events ( mainly peptic ulcer disease and gastrointestinal hemorrhage ) . Hypothesis To test the efficacy and tolerability of a 100-mg patch of ketoprofen applied once a day . Study Design R and omized controlled clinical trial ; Level of evidence , 1 . Methods The 2-week trial included patients suffering painful ( spontaneous pain ≥50 mm on a 0- to 100-mm visual analog scale ) , benign ( grade I or II ) , recent ( < 2 days ) ankle sprains as a model of general traumatic soft tissue injuries . The primary efficacy criterion was spontaneous pain change after 7 days of treatment in the intention-to-treat population . One hundred sixty-three patients were r and omized ( ketoprofen , 81 ; placebo , 82 ) . Results After 1 week of treatment , the decrease in spontaneous pain was -50 ± 20 mm for ketoprofen and -38 ± 24 mm for the placebo , showing a statistically significant intergroup difference ( P = . 0007 ) . The majority of the secondary criteria were also statistically significant in favor of the ketoprofen patch . Tolerance was good in both groups , adverse events being mostly local . Conclusion This trial suggested that a 7-day course of treatment with a ketoprofen patch is useful in benign ankle sprain , without revealing unexpected adverse events Diclofenac epolamine ( 2-hydroxyethyl-pyrrolidine ) ( DHEP ) is a diclofenac salt endowed with enhanced cutaneous permeation . To optimize its absorption after topical application , a lecithin-enriched DHEP 1.3 % gel has been developed ( DHEP lecithin gel ) and investigated in patients with shoulder periarthritis and lateral epicondylitis in a placebo-controlled , multicenter double-blind clinical trial . One hundred fifty-eight patients were r and omized to a 10-day treatment with DHEP lecithin gel or placebo ( 5 g t.i.d . applied on the painful area ) . The efficacy criteria were pain measured by visual analog scale ( VAS ) while performing a specific st and ardized movement , intake of rescue medication ( paracetamol ) , and the disabilities of the arm , shoulder and h and ( DASH ) question naire . VAS scores indicated a consistently higher analgesic activity of DHEP lecithin gel . At day 3 , pain was reduced by -20.1 + /- 20.2 and -9.9 + /- 12.7 mm in the DHEP lecithin gel- and placebo-treated patients , respectively ( p < 0.001 ) ; at day 6 of treatment , DHEP lecithin gel induced a pain reduction of -33.2 + /- 26.1 mm , while the reduction achieved with placebo was only -21.2 + /- 18.8 mm ( p < 0.001 ) . The mean changes in DASH question naire indicated that DHEP lecithin gel was more effective than placebo in improving patient well-being and reducing difficulties in performing the activities most severely impaired by rheumatism , while no difference was observed between the two treatments in consumption of rescue medication . In conclusion , these results indicate that DHEP lecithin gel is a topically effective analgesic product in patients with shoulder periarthritis or lateral epicondylitis and provide further evidence on the use of topical nonsteroidal anti-inflammatory drugs as an optimal approach to the treatment of localized musculoskeletal disorders A double-blind study was carried out in 120 patients who had received soft tissue injuries within the preceding 48 hours to compare the effectiveness of naproxen gel ( 10 % ) with placebo gel ( base alone ) . The injuries were predominantly synovitis and tendinitis . St and ard clinical evaluations of the patients ' condition were made by physicians and patients on entry and after 3 and 7 days of treatment . Both treatments result ed in a significant improvement in symptoms , but naproxen gel was significantly superior to placebo gel ( p less than 0.05 ) . The response produced by naproxen was more rapid ; all symptoms were significantly improved by Day 3 ( p less than 0.05 ) . The greater efficacy of naproxen was reflected in a lower usage of active drug compared with placebo which was consistent throughout the study . While the physicians ' global assessment s of the two gels did not differ significantly , the patients showed a preference in favour of naproxen ( p less than 0.05 ) Naproxen gel was well tolerated ; only 1 adverse event of itching occurred . It is suggested that naproxen gel offers an effective and convenient alternative to systemic non-steroidal anti-inflammatory drugs for patients where side-effects are to be avoided or when oral administration is undesirable & 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 It can be concluded from the research reported above that diclofenac diethylammonium ( NSAID ) in cases of professional swimmers and waterpolo players who have either an ache or suffered a severe hit , when applied externally offers rapid and excellent results The efficacy of a novel , proprietary topical formulation of ibuprofen 5 % gel ( Ibugel ) and ibuprofen 400 mg tablets ( 1200 mg daily ) was compared in a double-blind , double-dummy , parallel group study in patients with acute soft tissue injuries . Patients received either active gel plus placebo tablets ( n = 50 ) or active tablets plus placebo gel ( n = 50 ) for at least 7 days . The gel was applied and one tablet was taken three times daily . The two treatments showed similar efficacy . There were no significant differences between the groups for either the primary efficacy endpoint , the median time for the injury to be rated as ' completely better ' by the patients ( > 14 days active gel , 13.5 days active tablets ; P = 0.59 ) , or for other efficacy measures including the times to clinical ly significant relief from pain at rest or on movement and swelling . In summary , ibuprofen gel shows similar efficacy to oral ibuprofen 400 mg and may offer improved tolerability A parallel , double-blind , placebo controlled and r and omized study in a single center was done with ketoprofen 2.5 % gel to treat acute soft tissue injuries . Patients applied the gel twice a day for seven days , corresponding to 250 mg of ketoprofen per day . Assessment s were made on the third and seventh day by VAS , subjective evaluation and pain threshold algometry . The study group consisted of 29 patients and the control group 27 patients . Pain at rest was significantly relieved in the ketoprofen group , whereas in the placebo group the difference was not significant . In terms of side-effects , no difference between the groups was noticed . In both groups , local dermal irritation was found . Our results suggested that ketoprofen 2.5 % gel was safe and superior to placebo in the treatment of soft tissue injuries Sports-related soft tissue injuries , such as sprains , strains , and contusions , are a common painful condition . Current treatment includes oral nonsteroidal anti-inflammatory drugs ( NSAIDs ) , which have a high incidence of intolerable gastrointestinal side effects . Topically applied drugs have the potential to act locally in the soft tissues without systemic effects . This study assessed the efficacy and safety of topical diclofenac ( NSAID ) patch applied directly to the painful injury site for the treatment of acute minor sports injury pain . Adult subjects ( N = 222 ) were recruited from two communities for a multicenter , r and omized , placebo-controlled , parallel design study . All subjects had suffered a painful minor sports injury within the prior 72 hours of study entry . Either a diclofenac epolamine or placebo topical patch was applied directly to the skin overlying the painful injured site twice daily for 2 weeks . Measures of pain intensity were performed in a daily diary and at clinic visits on days 3 , 7 , and 14 . Diclofenac patch was superior to placebo patch in relieving pain . Statistical significance was seen on clinic days 3 ( P = 0.036 ) and 14 ( P = 0 . 048 ) , as well as the daily diary pain ratings at days 3 , 7 , and 14 ( P < or = 0.044 ) . No statistically significant differences were seen in any safety or side-effect measures with the diclofenac patch as compared to the placebo patch . Diclofenac epolamine patch is an effective and safe pain reliever for treatment of minor sports injury pain . The advantages of this novel therapy include its ease of use and lack of systemic side effects |
12,994 | 25,284,341 | The available evidence is insufficient to draw conclusions on the effects , primarily in terms of functional outcome and adverse events , of anabolic steroids , either separately or in combination with nutritional supplements , after surgical treatment of hip fracture in older people . | BACKGROUND Hip fracture occurs predominantly in older people , many of whom are frail and undernourished .
After hip fracture surgery and rehabilitation , most patients experience a decline in mobility and function .
Anabolic steroids , the synthetic derivatives of the male hormone testosterone , have been used in combination with exercise to improve muscle mass and strength in athletes .
They may have similar effects in older people who are recovering from hip fracture .
OBJECTIVES To examine the effects ( primarily in terms of functional outcome and adverse events ) of anabolic steroids after surgical treatment of hip fracture in older people . | BACKGROUND Anemia and malnutrition are significant complications in peritoneal dialysis ( PD ) patients . Previous studies in hemodialysis have shown that and rogens are effective as therapy for anemia ; however , this has not been tested in a r and omized prospect i ve trial in PD patients . Furthermore , the anabolic properties of and rogens may exert additional benefits on the nutritional status in this population . METHODS Twenty-seven stable male patients over 50 years who were under maintenance continuous ambulatory peritoneal dialysis ( CAPD ) therapy were r and omized to receive recombinant human erythropoietin ( rHuEPO ; N = 14 ) or n and rolone decanoate ( ND ; 200 mg/week IM ; N = 13 ) as therapy for anemia . The evolution of hematologic parameters and the impact on both nutritional anthropometric and biochemical variables were evaluated after six months of treatment . RESULTS Hemoglobin and hematocrit experienced similar increases in both groups : from 8.5 + /- 0.9 g/dL and 25.8 + /- 2.7 % to 11.7 + /- 0.6 g/dL and 34.7 + /- 1.6 % ( P < 0.001 ) in patients receiving rHuEPO , and from 8.9 + /- 0.8 and 27 + /- 2.2 % to 11.8 + /- 0.4 g/dL and 35.1 + /- 1.5 % ( P < 0.001 ) in subjects treated with ND . At the end of the study , out of the diverse nutritional variables included in this investigation , only weight and body mass index significantly increased in the rHuEPO group . Conversely , both anthropometric [ weight , body mass index , triceps skinfold , mid-arm circumference ( MAC ) and mid-arm muscle circumference ( MAMC ) ] and biochemical parameters ( serum total proteins , albumin , prealbumin and transferrin ) were significantly increased in patients treated with ND . In this group , serum urea nitrogen , urea net excretion and protein equivalent of nitrogen appearance significantly decreased . These facts , together with an increase in serum creatinine and no changes in dietary intake during the study , suggest a rise in muscle mass related to an anabolic effect of n and rolone decanoate . Interestingly , serum levels of insulin-like growth factor type 1 ( IGF-1 ) increased in patients on the and rogen group compared to subjects treated with rHuEPO . Moreover , there was a positive and significant correlation between the rise in IGF-1 concentrations and the increase in hemoglobin , hematocrit , MAC and MAMC . CONCLUSIONS And rogens therapy improved the anemia in elderly male CAPD patients in a similar manner to that observed with rHuEPO . Furthermore , compared with rHuEPO , and rogen administration was associated with beneficial effects on nutritional status . The mechanism of action of and rogens on hematologic and nutritional parameters might be mediated , at least in part , by IGF-1 AIM To evaluate the effects of a protein-rich liquid supplementation , alone or in combination with the anabolic steroid n and rolone decanoate , on body composition , activities of daily living ( ADL ) status and the health-related quality of life ( HRQoL ) after a femoral neck fracture . METHODS Sixty women , aged 83 + /- 5 years ( mean + /- SD ) , BMI < 24 kg/m2 ( 20.4 + /- 2 kg/m2 ) and capable of co-operating , with a femoral neck fracture treated with internal fixation , were r and omised to open treatment during 6 months with a protein-rich liquid formula alone ( PR , Fortimel , 200 ml/day , 20 g protein/day ) or in combination with n and rolone decanoate ( PR/N , Deca-Durabol 25 mg i.m./3 weeks ) or to a control group ( C ) . The patients were re-examined after 6 and 12 months regarding body weight ( BW ) , lean body mass ( LBM , DXA ) , ADL status according to Katz , HRQoL according to EQ 5-D and fracture healing . RESULTS LBM decreased in the C ( -1.2 + /- 2 kg ) and PR groups ( -1.2 + /- 1 kg ) but remained the same in the PR/N group ( 0.3 + /- 1 kg ) ( P < 0.05 between groups ) . ADL remained at a high level in the two intervention groups but declined significantly in the C group ( P < 0.005 between groups ) . The decline in HRQoL was least pronounced in the PR/N group at 6 months ( P < 0.05 between groups ) . Patients with fracture healing complications lost more BW ( P < 0.05 ) and LBM ( P < 0.01 ) than patients with uneventful fracture healing . CONCLUSION Protein-rich liquid supplementation in combination with n and rolone given for 6 months to lean elderly women after a femoral neck fracture may positively affect LBM , ADL and 59 elderly patients ( mean age 82 ) with femoral neck fractures were r and omised into two groups . 27 patients received daily an oral nutrition supplement ( 250 ml , 20 g protein , 254 kcal ) for a mean of 32 days ; 32 patients acted as controls . On admission most patients had nutritional deficiencies . Despite being offered adequate quantities , nutritional requirements were not met during the hospital stay . Clinical outcome was significantly better in the supplemented group ( 56 % favourable course vs 13 % in controls ) during the stay in the convalescent hospital . The rates of complications and deaths were also significantly lower in supplemented patients ( 44 % vs 87 % ) . 6 months after the fracture the rates of complications and mortality were significantly lower in supplemented patients ( 40 % vs 74 % ) . The median duration of hospital stay was significantly shorter in the supplemented group ( 24 vs 40 days ) . Thus the clinical outcome of elderly patients with femoral neck fracture can be improved by once daily dietary oral supplementation A total of 63 women who had an operation for a fracture of the hip was r and omly allocated to one year of treatment either with anabolic steroids , vitamin D and calcium ( anabolic group ) or with calcium only ( control group ) . The thigh muscle volume was measured by quantitative CT . The bone mineral density of the hip , femur and tibia was assessed by quantitative CT and dual-energy x-ray absorptiometry and of the heel by quantitative ultrasound . Quantitative CT showed that the anabolic group did not lose muscle volume during the first 12 months whereas the control group did ( p<0.01 ) . There was less bone loss in the proximal tibia in the anabolic group than in the control group . The speed of gait and the Harris hip score were significantly better in the anabolic group after six and 12 months . Anabolic steroids , even in this moderate dose , given in combination with vitamin D and calcium had a beneficial effect on muscle volume , bone mineral density and clinical function in this group of elderly women Objective : To evaluate ox and rolone , an oral anabolic steroid with potent anabolic activity and minimal and rogenic effects , for the treatment of AIDS‐associated myopathy and wasting . Methods : In a multicenter , double‐blind study , 63 HIV‐seropositive men with > 10 % loss of body weight were r and omized to receive either placebo , 5 mg/day ox and rolone , or 15 mg/day ox and rolone for 16 weeks . Body weight , neuromuscular evaluation , and measures of well‐being were repeatedly assessed . Results : Patients who received 15 mg/day ox and rolone showed weight gain throughout the 16‐week treatment period . Overall , the 5 mg/day ox and rolone group maintained their weight gain over the 16‐week period , whereas the placebo group showed continual weight loss . At week 16 , significantly more patients in the 15 mg/day dose group reported increases in appetite and activity than those receiving placebo . There were no consistent , dose related , statistically significant differences from baseline in laboratory values or adverse events . Conclusion : Ox and rolone , at a dose of either 5 mg/day or 15 mg/day , in contrast to placebo , had a positive impact on the weight and well‐being of HIV‐seropositive patients suffering from wasting and weakness . Measurable improvement in muscle strength was not noted at the doses employed in this study . Ox and rolone was well tolerated in all the patients who were enrolled in the study Based on the results reported here , additional studies using higher doses of ox and rolone seem warranted Abstract As the world population ages , the prevalence of osteoporosis and the incidence of hip fractures will increase dramatically , being responsible for an increase of the health expenditure . On the other h and , there is the inescapable fact of scarcity creating the necessity of making difficult choices with regard to the allocation of human re sources . So the question remains : should we carry on investing an important part of our health expenditure for the treatment of hip fractures in elderly people ? To answer this statement , we compared 384 hip fracture patients of 70 years and older treated in our department between 1978 and 1983 with 1102 patients treated between 1998 and 2003 . Both groups had a prospect i ve follow-up of at least one year . There were no statistically significant differences : mortality rate 24 % vs. 23 % ; good functional outcome 82 % vs. 73 % ; and home going rate 60 % vs. 66 % . The factors influencing these results were studied . So we can conclude : -The number of hip fractures treated nowadays has increased compared with twenty years ago ; -There is no significant improvement in mortality , nor in quality of life ; -Age is not a contraindication for hip fracture surgery BACKGROUND We examined the effects of hip fracture on mortality , entry into long-term institutional care , and new evidence of poverty . We estimate of the proportion of hip fracture patients who require not just short-term rehabilitation but who become dependent on long-term institutional care , and the risk of becoming newly dependent on Medicaid or eligible for low-income subsidies following hip fracture . METHODS We used data from 2005 through 2010 for a r and om 5 % sample of Medicare beneficiaries ( N = 3.1 million ) to conduct a retrospective matched cohort study . We used high-dimensional propensity score matching to compare outcomes for patients who experienced a hip fracture with subjects who did not , but had similar propensity for suffering a hip fracture . We then compared the 1-year risk of death , debility , and destitution between groups . RESULTS We matched 43,210 hip fracture patients to comparators without a hip fracture . Hip fractures were associated with more than a twofold increase in likelihood of mortality ( incidence proportion ratio [ IPR ] of 2.27 , 95 % CI , 2.20 - 2.34 ) , a fourfold increase in likelihood of requiring long-term nursing facility care ( IPR , 3.96 ; 95 % CI , 3.77 - 4.16 ) , and a twofold increase in the probability of entering into low-income status ( IPR , 2.14 ; 95 % CI 1.99 - 2.31 ) within 1 year following hip fracture compared with subjects without a hip fracture . CONCLUSIONS Hip fracture in elderly patients result ed in increased death , debility , and destitution . Initiatives that lead to improved treatment of osteoporosis could result in a decrease in incidence of fractures , subsequent death , debility , and destitution for older adults Background Hip fractures in the elderly are followed by considerable risk of functional decline and mortality . Questions / purpose sThe purpose s of this study were to ( 1 ) explore predictive factors of functional level at discharge , ( 2 ) evaluate 1-year mortality after hip fracture compared with that of the general population , and ( 3 ) evaluate the affect of early functional outcome on 1-year mortality in patients operated on for hip fractures . Methods A total of 228 consecutive patients ( average age , 77.6 ± 7.4 years ) with hip fractures who met the inclusion criteria were enrolled in an open , prospect i ve , observational cohort study . Functional level at discharge was measured with the motor Functional Independence Measure ( FIM ) score , which is the most widely accepted functional assessment measure in use in the rehabilitation community . Mortality rates in the study population were calculated in absolute numbers and as the st and ardized mortality ratio . Multivariate regression analysis was used to explore predictive factors for motor FIM score at discharge and for 1-year mortality adjusted for important baseline variables . Results Age , health status , cognitive level , preinjury functional level , and pressure sores after hip fracture surgery were independently related to lower discharge motor FIM scores . At 1-year followup , 57 patients ( 25 % ; 43 women and 14 men ) had died . The 1-year hip fracture mortality rate compared with that of the general population was 31 % in our population versus 7 % for men and 23 % in our population versus 5 % for women 65 years or older . The 1-year st and ardized mortality rate was 341.3 ( 95 % CI , 162.5–520.1 ) for men and 301.6 ( 95 % CI , 212.4–391.8 ) for women , respectively . The all-cause mortality rate observed in this group was higher in all age groups and in both sexes when compared with the all-cause age-adjusted mortality of the general population . Motor FIM score at discharge was the only independent predictor of 1-year mortality after hip fracture . Conclusions Functional level at discharge is the main determinant of long-term mortality in patients with hip fracture . Motor FIM score at discharge is a reliable predictor of mortality and can be recommended for clinical use . Level of Evidence Level II , prognostic study . See Guidelines for Authors for a complete description of levels of evidence The primary aim of this study was to evaluate the effect of two different surgical methods on nutritional status and functional capacity during the first postoperative year in patients with displaced femoral neck fractures . A further aim was to evaluate the effect of nutritional support . One hundred patients were r and omly assigned to treatment with either primary total hip arthroplasty ( THA ) or osteo synthesis . Half of the patients in each treatment group received protein- and energy-enriched food in the hospital in addition to individual nutritional advice in order to optimize their intake of protein- and energy-rich food . Nutritional state and functional capacity were examined at baseline , one and three months , and one year after the operation . Pain was examined at three months and one year . The effect of nutritional intervention was equal within both surgical groups . Logistic regression showed that the dependent variable “ living at one year ” was significantly associated with serum albumin levels at one month . Advanced age , mental impairment and deteriorated nutritional status were predominant in the non-survivors . Overall , the primary THA group performed better compared with the osteo synthesis group concerning weight change over time , locomotion and pain . This study also showed that primary THA could safely be performed in the elderly without an increased postoperative mortality rate OBJECTIVES The purpose of this study was to prospect ively assess the independent effect of hip fracture on mortalìty , hospitalization , and functional status . METHODS Among 7527 members of the Longitudinal Study of Aging who were over age 70 at baseline , 368 persons with hip fracture occurring between 1984 and 1991 were identified . Median length of follow-up was 831 days . RESULTS Hip fracture was significantly related to mortality ( adjusted hazards ratio [ AHR ] = 1.83 ; 95 % confidence interval [ CI ] = 1.55 , 2.16 ) when treated as a time-dependent covariate . This effect was concentrated in the first 6 months postfracture ( AHR = 38.93 , 95 % CI = 29.58 , 51.23 , vs AHR = 1.17 ; 95 % CI = 0.95 , 1.44 ) . Hip fracture significantly increased the likelihood of subsequent hospitalization ( adjusted odds ratio = 3.31 , 95 % CI = 2.64 , 4.15 ) and increased the number of subsequent episodes by 9.4 % , the number of hospital days by 21.3 % , and total charges by 16.3 % . Hip fracture also increased the number of functional status dependencies . CONCLUSIONS The health of older adults deteriorates after hip fracture , and efforts to reduce the incidence of hip fracture could lower subsequent mortality , morbidity , and health services use Two hundred and seventy-five consecutive patients over the age of 50 years admitted with a hip fracture were prospect ively studied in detail , to assess the impact of a hip fracture on their functional ability and their need for social support . One hundred and eighty-three ( 66.9 % ) patients survived to 1 year . Mortality was highest amongst those least able to perform the recorded activities . One hundred and fifty-eight ( 86 % ) of the survivors were resident in the same level of accommodation after 1 year . There was a reduction in mobility and related functions of 20 - 25 % and a reduction of 5 % in tasks not related to hip function . It is therefore estimated that in the year after a hip fracture there will be decline in functionally abilities of about 5 % unrelated to the hip fracture and about 15 - 20 % directly related to the hip fracture . There was an increase in the requirement for social support amongst survivors individually , but overall the total economic burden on social services and institutional care was not significantly changed by hip fracture The role of calcitonin in the aetiology of postmenopausal osteoporosis remains uncertain . Oestrogen , an established therapy for postmenopausal osteoporosis , has been shown to enhance calcitonin secretion . In order to assess whether two other osteoporotic drug treatments , oral calcium and stanozolol ( an anabolic steroid ) , may also affect calcitonin secretion , 20 elderly women with femoral neck fracture were r and omly selected to receive either 880 mg calcium or 5 mg stanozolol daily for 12 weeks . Basal calcitonin and serum calcium were not altered significantly by either treatment . The calcitonin response to a 10 min infusion of calcium was enhanced following treatment with oral calcium but not stanozolol . This suggests one possible mechanism of action whereby calcium may exert its antiresorptive effect on bone and supports the use of oral calcium in the treatment of postmenopausal osteoporosis As men age , serum testosterone concentrations decrease , the percentage of body mass that is fat increases , the percentage of lean body mass decreases , and muscle strength decreases . Because these changes are similar to those that occur in hypogonadal men , we hypothesized that increasing the serum testosterone concentration of men over 65 yr of age to that in young men would decrease their fat mass , increase their lean mass , and increase their muscle strength . We r and omized 108 men over 65 yr of age to wear either a testosterone patch or a placebo patch in a double blind study for 36 months . We measured body composition by dual energy x-ray absorptiometry and muscle strength by dynamometer before and during treatment . Ninety-six men completed the entire 36-month protocol . Fat mass decreased ( -3.0+/-0.5 kg ) in the testosterone-treated men during the 36 months of treatment , which was significantly different ( P = 0.001 ) from the decrease ( -0.7+/-0.5 kg ) in the placebo-treated men . Lean mass increased ( 1.9+/-0.3 kg ) in the testosterone-treated men , which was significantly different ( P < 0.001 ) from that ( 0.2+/-0.2 kg ) in the placebo-treated men . The decrease in fat mass in the testosterone-treated men was principally in the arms ( -0.7+/-0.1 kg ; P < 0.001 compared to the placebo group ) and legs ( -1.1+/-0.2 kg ; P < 0.001 ) , and the increase in lean mass was principally in the trunk ( 1.9+/-0.3 kg ; P < 0.001 ) . The change in strength of knee extension and flexion at 60 degrees and 180 degrees angular velocity during treatment , however , was not significantly different between the two groups . We conclude that increasing the serum testosterone concentrations of normal men over 65 yr of age to the midnormal range for young men decreased fat mass , principally in the arms and legs , and increased lean mass , principally in the trunk , but did not increase the strength of knee extension and flexion , as measured by dynamometer UNLABELLED Most hip fractures occur in subjects without osteoporosis and are associated with a fall . Conventional menopausal hormone therapy ( HT ) improves postural balance , which might explain the rapid reduction in hip fracture risk . It is unclear whether tibolone improves postural balance , which might determine its effects on peripheral fracture risk . OBJECTIVE To study the short-term effects of low-dose tibolone therapy on postural balance in elderly women . METHODS Eighty healthy women ( 70 evaluable ) , aged 60 years or more , were recruited through advertising in the local media . They were r and omly allocated to receive either tibolone ( 1.25 mg/d ) or placebo for 6 months . Postural balance was assessed as sway velocity , using a force platform . RESULT ( S ) Baseline characteristics , including serum estradiol values and postural balance , were similar in the two study groups . On average , the overall dosing compliance was very high , over 97 % in both groups . After 6 months , sway velocity had decreased ( improved ) by 7.6 % ( -0.97 cm/s ; P=0.16 vs. baseline ) in the tibolone arm and by 2.5 % ( -0.30 cm/s ; P=0.59 vs. baseline ) in the placebo group . The difference 0.67 cm/s was not statistically significant ( 95 % CI -2.44 , 1.10 ; P=0.45 ) . Adjustments for age , serum estradiol level and variable value at baseline , revealed similar results . CONCLUSIONS Short-term treatment with tibolone ( 1.25 mg/d ) , compared to placebo , did not significantly affect postural balance function in elderly women OBJECTIVE To determine the safety and efficacy of the anabolic steroid n and rolone in elderly patients with hip fractures . DESIGN A r and omized double-blind placebo-controlled trial . SETTING The orthopedic ward of a university teaching hospital . PARTICIPANTS 29 frail elderly females with hip fractures . INTERVENTION Subjects received n and rolone 2 mg/kg ( n = 15 ) or placebo ( n = 14 ) by weekly injection for 4 weeks or until discharge . MEASURES Baseline functional status was assessed by the Lawton-Brody ADL and IADL . Hemoglobin , transferrin , thyroid-binding prealbumin , albumin , liver function tests , creatinine , weight , MAMC , bioelectric impedance , st and ard anthropometrics and grip strength were measured at baseline and weekly intervals . Rehabilitation parameters and length of stay were recorded . RESULTS The placebo and n and rolone groups were similar in age , although the control group had slightly higher baseline ADL scores . There was no difference between groups in biochemical parameters , anthropometrics , body composition , grip strength , rehabilitation end points or length of stay . One subject in the n and rolone group had a doubling of AST and was withdrawn from the study . CONCLUSIONS N and rolone can be given safely to frail elderly subjects with hip fractures but is likely to be of minimal benefit at the doses we employed BACKGROUND & AIMS Osteoporosis is a major health problem worldwide . Low weight is a major risk factor for low bone mass and fractures . The aim of this study was to investigate the effects on bone tissue of protein-rich supplementation alone or in combination with n and rolone decanoate in lean elderly women after a hip fracture . METHODS Sixty elderly women with BMI < 24 kg/m(2 ) admitted to hospital due to a femoral neck fracture were r and omised to a control group , to receive a protein-rich formula or to receive the same formula with an addition of n and rolone decanoate for 6 months . All patients received additional calcium and vitamin D. The effects after 6 and 12 months were measured by means of bone mineral density ( BMD ) using dual-energy X-ray absorptiometry ( DXA ) , and with biochemical bone markers . Osteocalcin and C-terminal telopeptide of collagen-1 ( CTX ) were used to estimate bone formation and bone resorption , respectively . RESULTS The analyses showed an increase in total body BMD at 6 and 12 months in patients who received protein-rich supplementation . N and rolone decanoate did not appear to have any additional effect on BMD . Osteocalcin increased in all groups while no significant changes were found for CTX . CONCLUSION The overall results of the study indicated that protein-rich supplementation given to lean elderly female hip fracture patients increased the total body BMD The worldwide increase in hip fractures is a major challenge to the health care system and society . The proper treatment of femoral neck fractures in the elderly is still controversial , and even more so from an international perspective . Optimising the treatment for improved outcomes and a reduced need for secondary surgery is m and atory for humanitarian and economical reasons . The importance of incorporating the patient 's perspective of the outcome in clinical trials has been acknowledged and there are now numerous instruments for assessing the quality of life . We evaluated two quality of life instruments , the EQ-5D and the SF-36 , in patients with femoral neck fractures and also measured the quality of life two years after different interventions . The EQ-5D was vali date d in two prospect i ve studies and it appeared to be an appropriate quality of life instrument in elderly patients with femoral neck fractures . There was a good correlation between the quality of life ( EQ-5D index scores ) and other outcome measures such as pain , mobility and independence in activities of daily living ( ADL ) . The results also showed high responsiveness , i.e. , ability to capture clinical ly important changes , for both the EQ-5D and the SF-36 . The question naire response rate for both instruments was high . The rated prefracture EQ-5D index scores showed good correspondence with the scores of an age-matched Swedish reference population . The quality of life in patients with femoral neck fractures treated with internal fixation ( IF ) decreased , particularly in patients with fracture healing complications . The fracture healing complications rate at two years in patients with displaced femoral neck fractures treated with IF was 36 % compared with 7 % in patients with undisplaced fractures . The quality of life of patients with uneventfully healed fractures at two year was lower in patients with primary displaced fractures than in patients with primary undisplaced fractures . In a prospect i ve r and omised trial , patients with displaced femoral neck fractures were r and omised to IF or total hip replacement ( THR ) . IF result ed in more complications than THR , 36 % versus 4 % , and necessitated more reoperations , 42 % versus 4 % . Hip function and quality of life ( EQ-5D ) were generally better in the THR group . In summary , THR yielded a better outcome than IF for an elderly , relatively healthy , lucid patient with a displaced femoral neck fracture . In a study of elderly women with femoral neck fractures , nearly half of the patients displayed signs of protein-energy malnutrition . Underweight was associated with muscle fatigue , cognitive dysfunction and a low quality of life ( Nottingham Health Profile ) . In a prospect i ve r and omised trial , protein-rich liquid supplementation in combination with an anabolic steroid given for 6 months to lean elderly women after a femoral neck fracture was shown to positively affect lean body mass , ADL and quality of life ( EQ-5D ) . Fracture healing complications had a negative impact on body weight , lean body mass and quality of life Three hundred thirty-six community-dwelling , previously ambulatory , geriatric patients with hip fracture were observed prospect ively to determine ambulatory ability at a minimum follow up of 1 year . One hundred thirty-seven ( 41 % ) patients maintained their pre-fracture ambulatory ability at a minimum followup of 1 year ; 134 ( 40 % ) patients remained ambulatory but became more dependent on assistive devices ; 39 ( 12 % ) previous community ambulators became household ambulators , and 26 ( 8 % ) patients became nonfunctional ambulators . Analysis was performed to determine which pre- and postinjury factors were predictive of failure to recover ambulatory capacity 1 year after fracture . Potential predictor variables analyzed included age , gender , number of comorbid conditions , pre-fracture ambulatory ability , prefracture living situation , fracture type , American Society of Anesthesiologists rating of operative risk , type of surgery , and number of postoperative complications . Multiple logistic regression analysis identified significant contributions of age , prefracture ambulatory ability , American Society of Anesthesiologists rating of operative risk , and fracture type to ambulatory recovery OBJECTIVE To study appetite and food choices in lean elderly women at the time of a femoral neck fracture and after 6 months of nutritional and anabolic intervention . SUBJECTS AND METHODS Forty-five nondemented women > 70 years of age ( mean + /- SD : 83 + /- 5 years ) with a recent hip fracture and body mass index < 24 kg/m2 ( mean : 20.5 + /- 2.3 ) were interviewed about their appetite and dietary habits prior to fracture . The patients were r and omized to treatment with a protein-rich liquid supplement ( PR ; 200 kcal and 20 g protein day(-1 ) ) alone or in combination with n and rolone decanoate injections ( PR/N ) 25 mg i.m . every third week or to a control group ( C ) . A second interview was conducted 6 months later . RESULTS Reduced appetite before the fracture was reported by 60 % . Half of the patients did not have dessert with any of their daily meals , one-third used low-fat margarines and one-third drank water with their meals . The estimated mean daily energy intake was 6.4 + /- 1.2 MJ ( 1541 + /- 304 kcal ) indicating that three of four subjects did not meet their energy needs . At 6 months , 40 % reported reduced appetite . There was no difference in the change of appetite between the three r and omized groups . Still , half of the subjects appeared to not meet their energy needs . Protein intake increased in the PR and PR/N groups , in contrast to the controls ( P = 0.002 ) . CONCLUSION Reduced appetite and insufficient energy intake was recorded in lean elderly women with a femoral neck fracture . Nutritional supplementation alone or in combination with an anabolic steroid increased protein intake without adversely affecting appetite Eighty-eight postmenopausal women with at least one vertebral collapse were r and omly assigned to two groups of 44 patients each . All patients were treated for a period of 12 months with 50 mg of n and rolone decanoate every 3 weeks or 1 microgram of 1-alpha-hydroxy-calciferol daily . Both groups received an identical placebo of the inactive drug . Pain intensity was significantly decreased in the n and rolone group and mobility was improved . Patients treated with vitamin D metabolite had also a beneficial but less obvious clinical result . Bone mineral measurements showed an increase of 5 % in the n and rolone decanoate group , but a 2.5 % decrease in the vitamin D metabolite group . Biochemical results showed a significant hypercalciuric effect of vitamin D metabolite , while n and rolone decanoate caused a reduction in calcium/creatinine excretion . No difference in serum lipids was found during the annual treatment in both groups . It is concluded that n and rolone decanoate has a beneficial effect in clinical symptoms , bone mineral density and biochemical parameters in patients with established osteoporotic vertebral fractures |
12,995 | 19,143,033 | Beneficial adaptations to exercise were seen primarily in muscle fiber area and capillary density , glycogen , glycogen synthase and GLUT4 protein expressions . | The aim of this investigation was to review morphological and metabolic adaptations within skeletal muscle to exercise training in adults with type 2 diabetes mellitus ( T2DM ) or impaired glucose tolerance ( IGT ) . | Carbohydrate metabolism was assessed in 20 glucose-intolerant subjects before and after 12 wk on a high-carbohydrate diet ( HC ) or the diet combined with exercise training ( HC-EX ) . The diet provided 60 % of energy as carbohydrate and 20 % as fat . Neither treatment altered fasting glucose or insulin concentrations or their response to a meal . During a glucose clamp ( 216 pmol insulin/L ) glucose disposal increased from 13.2 + /- 0.83 to 14.6 + /- 0.83 mumol.kg fat-free mass-1.min-1 ( P < 0.05 ) in both groups . During more pronounced hyperinsulinemia ( 654 pmol/L ) glucose disposal did not change significantly ( 49.9 + /- 3.8 to 50.7 + /- 3.8 mumol.kg fat-free mass-1.min-1 ) . Muscle glycogen increased in the HC-EX group ( 78.5 + /- 8.1 to 161.1 + /- 15.7 mmol glucose/kg muscle ) , with no changes in the HC group . These results do not support the recommendation to increase the dietary carbohydrate content for improving postpr and ial glucose metabolism or insulin action in glucose-intolerant adults unless combined with exercise training , which promotes muscle glycogen storage Circulating adiponectin is reduced in disorders associated with insulin resistance . This study was conducted to determine whether an exercise/diet intervention would alter adiponectin multimer distribution and adiponectin receptor expression in skeletal muscle . Impaired glucose-tolerant older ( > 60 yr ) obese ( BMI 30 - 40 kg/m(2 ) ) men ( n = 7 ) and women ( n = 14 ) were r and omly assigned to 12 wk of supervised aerobic exercise combined with either a hypocaloric ( ExHypo , approximately 500 kcal reduction , n = 11 ) or eucaloric diet ( ExEu , n = 10 ) . Insulin sensitivity was determined by the euglycemic ( 5.0 mM ) hyperinsulinemic ( 40 mU x m(-2 ) x min(-1 ) ) clamp . Adiponectin multimers [ high ( HMW ) , middle ( MMW ) , and low molecular weight ( LMW ) ] were measured by nondenaturing Western blot analysis . Relative quantification of adiponectin receptor expression through RT-PCR was determined from skeletal muscle biopsy sample s. Greater weight loss occurred in ExHypo compared with ExEu subjects ( 8.0 + /- 0.6 vs. 3.2 + /- 0.6 % , P < 0.0001 ) . Insulin sensitivity improved postintervention in both groups ( ExHypo : 2.5 + /- 0.3 vs. 4.4 + /- 0.5 mg x kg FFM(-1 ) x min(-1 ) , and ExEu : 2.9 + /- 0.4 vs. 4.1 + /- 0.4 mg x kg FFM(-1 ) x min(-1 ) , P < 0.0001 ) . Comparison of multimer isoforms revealed a decreased percentage in MMW relative to HMW and LMW ( P < 0.03 ) . The adiponectin SA ratio ( HMW/total ) was increased following both interventions ( P < 0.05 ) and correlated with the percent change in insulin sensitivity ( P < 0.03 ) . Postintervention adiponectin receptor mRNA expression was also significantly increased ( AdipoR1 P < 0.03 , AdipoR2 P < 0.02 ) . These data suggest that part of the improvement in insulin sensitivity following exercise and diet may be due to changes in the adiponectin oligomeric distribution and enhanced membrane receptor expression To evaluate the effects of endurance training on the expression of monocarboxylate transporters ( MCT ) in human vastus lateralis muscle , we compared the amounts of MCT1 and MCT4 in total muscle preparations ( MU ) and sarcolemma-enriched ( SL ) and mitochondria-enriched ( MI ) fractions before and after training . To determine if changes in muscle lactate release and oxidation were associated with training-induced changes in MCT expression , we correlated b and densities in Western blots to lactate kinetics determined in vivo . Nine weeks of leg cycle endurance training [ 75 % peak oxygen consumption ( VO(2 peak ) ) ] increased muscle citrate synthase activity ( + 75 % , P < 0.05 ) and percentage of type I myosin heavy chain ( + 50 % , P < 0.05 ) ; percentage of MU lactate dehydrogenase-5 ( M4 ) isozyme decreased ( -12 % , P < 0.05 ) . MCT1 was detected in SL and MI fractions , and MCT4 was localized to the SL . Muscle MCT1 contents were consistent among subjects both before and after training ; in contrast , MCT4 contents showed large interindividual variations . MCT1 amounts significantly increased in MU , SL , and MI after training ( + 90 % , + 60 % , and + 78 % , respectively ) , whereas SL but not MU MCT4 content increased after training ( + 47 % , P < 0.05 ) . Mitochondrial MCT1 content was negatively correlated to net leg lactate release at rest ( r = -0.85 , P < 0.02 ) . Sarcolemmal MCT1 and MCT4 contents correlated positively to net leg lactate release at 5 min of exercise at 65 % VO(2 peak ) ( r = 0.76 , P < 0.03 and r = 0 . 86 , P < 0.01 , respectively ) . Results support the conclusions that 1 ) endurance training increases expression of MCT1 in muscle because of insertion of MCT1 into both sarcolemmal and mitochondrial membranes , 2 ) training has variable effects on sarcolemmal MCT4 , and 3 ) both MCT1 and MCT4 participate in the cell-cell lactate shuttle , whereas MCT1 facilitates operation of the intracellular lactate shuttle OBJECTIVE To determine the efficacy of high-intensity progressive resistance training ( PRT ) on glycemic control in older adults with type 2 diabetes . RESEARCH DESIGN AND METHODS We performed a 16-week r and omized controlled trial in 62 Latino older adults ( 40 women and 22 men ; mean + /- SE age 66 + /- 8 years ) with type 2 diabetes r and omly assigned to supervised PRT or a control group . Glycemic control , metabolic syndrome abnormalities , body composition , and muscle glycogen stores were determined before and after the intervention . RESULTS Sixteen weeks of PRT ( three times per week ) result ed in reduced plasma glycosylated hemoglobin levels ( from 8.7 + /- 0.3 to 7.6 + /- 0.2 % ) , increased muscle glycogen stores ( from 60.3 + /- 3.9 to 79.1 + /- 5.0 mmol glucose/kg muscle ) , and reduced the dose of prescribed diabetes medication in 72 % of exercisers compared with the control group , P = 0.004 - 0.05 . Control subjects showed no change in glycosylated hemoglobin , a reduction in muscle glycogen ( from 61.4 + /- 7.7 to 47.2 + /- 6.7 mmol glucose/kg muscle ) , and a 42 % increase in diabetes medications . PRT subjects versus control subjects also increased lean mass ( + 1.2 + /- 0.2 vs. -0.1 + /- 0.1 kg ) , reduced systolic blood pressure ( -9.7 + /- 1.6 vs. + 7.7 + /- 1.9 mmHg ) , and decreased trunk fat mass ( -0.7 + /- 0.1 vs. + 0.8 + /- 0.1 kg ; P = 0.01 - 0.05 ) . CONCLUSIONS PRT as an adjunct to st and ard of care is feasible and effective in improving glycemic control and some of the abnormalities associated with the metabolic syndrome among high-risk older adults with type 2 diabetes Hispanics are at increased risk of morbidity and mortality due to their high prevalence of diabetes and poor glycemic control . Strength training is the most effective lifestyle intervention to increase muscle mass but limited data is available in older adults with diabetes . We determined the influence of strength training on muscle quality ( strength per unit of muscle mass ) , skeletal muscle fiber hypertrophy , and metabolic control including insulin resistance ( Homeostasis Model Assessment –HOMA-IR ) , C-Reactive Protein ( CRP ) , adiponectin and Free Fatty Acid ( FFA ) levels in Hispanic older adults . Sixty-two community-dwelling Hispanics ( > 55 y ) with type 2 diabetes were r and omized to 16 weeks of strength training plus st and ard care ( ST group ) or st and ard care alone ( CON group ) . Skeletal muscle biopsies and biochemical measures were taken at baseline and 16 weeks . The ST group show improved muscle quality ( mean±SE : 28±3 ) vs CON ( -4±2 , p<0.001 ) and increased type I ( 860±252µm2 ) and type II fiber cross-sectional area ( 720±285µm2 ) compared to CON ( type I : -164±290µm2 , p=0.04 ; and type II : -130±336µm2 , p=0.04 ) . This was accompanied by reduced insulin resistance [ ST : median ( interquartile range ) -0.7(3.6 ) vs CON : 0.8(3.8 ) , p=0.05 ] ; FFA ( ST : -84±30µmol/L vs CON : 149±48µmol/L , p=0.02 ) ; and CRP [ ST : -1.3(2.9)mg/L vs CON : 0.4(2.3)mg/L , p=0.05 ] . Serum adiponectin increased with ST [ 1.0(1.8)µg/mL ] compared to CON [ -1.2(2.2)µg/mL , p<0.001 ] . Strength training improved muscle quality and whole-body insulin sensitivity . Decreased inflammation and increased adiponectin levels were related with improved metabolic control . Further studies are needed to underst and the mechanisms associated with these findings . However , these data show that strength training is an exercise modality to consider as an adjunct of st and ard of care in high risk population s with type 2 diabetes We examined the expression of the sodium-dependent glucose co-transporter system ( hSGLT3 ) in skeletal muscle of Hispanic older adults with type 2 diabetes . Subjects ( 65±8 yr ) were r and omized to resistance training ( 3x/wk , n=13 ) or st and ard of care ( controls , n=5 ) for 16 weeks . Skeletal muscle hSGLT3 and GLUT4 mRNA transcript levels were determined by real time RT-PCR . hSGLT3 transcripts increased by a factor of ten following resistance training compared to control subjects ( 0.10 , P=0.03 ) . There were no differences in GLUT4 mRNA expression levels between groups . Protein expression levels of these transporters were confirmed by immunohistochemistry and Western blotting . hSGLT3 after resistance exercise was found not to be co-localized with the nicotinic acetylcholine receptor . The change in hSGLT3 transcript levels in the vastus lateralis muscle was positively correlated with glucose uptake , as measured by the change in muscle glycogen stores ( r=0.53 , P=0.02 ) ; and with exercise intensity , as measured by the change in muscle strength ( r=0.73 , P=0.001 ) . Group assignment was be the only independent predictor of hSGLT3 transcript levels , explaining 68 % of its variability ( P=0.01 ) . Our data show that hSGLT3 , but not GLTU4 , expression was enhanced in skeletal muscle after 16 weeks of resistance training . This finding suggests that hSGLT3 , an insulin-independent glucose transporter , is activated with exercise and it may play a significant role in glycemic control with muscle contraction . The hSGLT3 exact mechanism is not well understood and requires further investigation . However its functional significance regarding a reduction of glucose toxicity and improvement of insulin resistance is the subject of ongoing research OBJECTIVE To determine the feasibility and the benefits of combined resistance and interval exercise training on phenotype characteristics and skeletal muscle function in deconditioned , type 2 diabetes ( T2D ) patients with polyneuropathy . DESIGN Short-term , single-arm intervention trial . METHODS Eleven male T2D patients ( age : 59.1+/-7.5 years ; body mass index : 32.2+/-4.0 kg/m2 ) performed progressive resistance and interval exercise training thrice a week for 10 weeks . Besides primary diabetes outcome measures , muscle strength ( MUST ) , maximal workload capacity ( Wmax ) , whole-body peak oxygen uptake ( VO2peak ) and muscle oxidative capacity ( MUOX ) , intramyocellular lipid ( IMCL ) and glycogen ( IMCG ) storage , and systemic inflammation markers were determined before and after training . Daily exogenous insulin requirements ( EIR ) and historic individualized EIR were gathered and analysed . RESULTS MUST and Wmax increased with 17 % ( 90 % confidence intervals 9 - 24 % ) and 14 % ( 6 - 21 ) respectively . Furthermore , mean arterial blood pressure declined with 5.5 mmHg ( -9.7 to -1.4 ) . EIR dropped with 5.0 IU/d ( -11.5 to 1.5 ) compared with baseline . A decline of respectively -0.7 mmol/l ( -2.9 to 1.5 ) and -147 micromol/l ( -296 to 2 ) in fasting plasma glucose and non-esterified fatty acids concentrations were observed following the intervention , but these were not accompanied by changes in VO2peak , MUOX , IMCL or IMCG , and blood glycolysated haemoglobin , adiponectin , tumor necrosis factor-alpha and /or cholesterol concentrations . CONCLUSION Short-term resistance and interval exercise training is feasible in deconditioned T2D patients with polyneuropathy and accompanied by moderate improvements in muscle function and blood pressure . Such a specific exercise regimen may provide a better framework for future exercise intervention programmes in the treatment of deconditioned T2D patients Resistance training results in muscle hypertrophy and improves glycemic control in patients with type 2 diabetes . Whether resistance training modulates inflammation in muscles of diabetic patients remains unknown . We examined the expression of genes encoding the cytokines , tumor necrosis factor-α ( TNF-α ) , interleukin-1β ( IL-lβ ) and transforming growth factor-β , ( TGF-β , ) as well as the pan-leukocyte marker CD18 . Thirty men and women ( 67 ± 7 years ) were r and omized to either 16 weeks of resistance training and usual diabetes care ( EX ) or to usual diabetes care only ( CON ) . Muscle biopsies were obtained from the vastus lateralis muscle prior to the 16-week intervention , and 72 h following the maximal strength test post-intervention . Fiber cross-sectional area ( CSA ) was determined following ATPase staining . Cytokine and CD18 transcript levels were assessed by real-time PCR . Resistance training increased CSA of type I and II fibers ( both P < 0.05 ) and IL-1β transcript levels ( P = 0.05 ) . TNF-α ( P < 0.05 ) and TGF-β1 transcripts ( P < 0.05 ) increased over time in the EX group , but these increases did not differ from those in the CON group . In both groups , the increase in CD18 transcripts remained minimal . The two groups differ by the relationship between changes in CD18 and changes in cytokine transcripts , suggesting that resistance training affects the source of cytokines in muscle . Our studies establish that resistance training in older adults with type 2 diabetes results in muscle fiber hypertrophy , despite a greater accumulation of inflammatory cytokine transcripts in muscle Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists Twelve male subjects with recreational resistance training background s completed 12 wk of intensified resistance training ( 3 sessions/wk ; 8 exercises/session ; 3 sets/exercise ; 10 repetitions maximum/set ) . All major muscle groups were trained , with four exercises emphasizing the forearm flexors . After training , strength ( 1-repetition maximum preacher curl ) increased by 25 % ( P < 0.05 ) . Magnetic resonance imaging scans revealed an increase in the biceps brachii muscle cross-sectional area ( CSA ) ( from 11.8 + /- 2.7 to 13.3 + /- 2.6 cm2 ; n = 8 ; P < 0.05 ) . Muscle biopsies of the biceps brachii revealed increases ( P < 0.05 ) in fiber areas for type I ( from 4,196 + /- 859 to 4,617 + /- 1,116 microns2 ; n = 11 ) and II fibers ( from 6,378 + /- 1,552 to 7,474 + /- 2,017 microns2 ; n = 11 ) . Fiber number estimated from the above measurements did not change after training ( 293.2 + /- 61.5 x 10(3 ) pretraining ; 297.5 + /- 69.5 x 10(3 ) posttraining ; n = 8) . However , the magnitude of muscle fiber hypertrophy may influence this response because those subjects with less relative muscle fiber hypertrophy , but similar increases in muscle CSA , showed evidence of an increase in fiber number . Capillaries per fiber increased significantly ( P < 0.05 ) for both type I ( from 4.9 + /- 0.6 to 5.5 + /- 0.7 ; n = 10 ) and II fibers ( from 5.1 + /- 0.8 to 6.2 + /- 0.7 ; n = 10 ) . No changes occurred in capillaries per fiber area or muscle area . In conclusion , resistance training result ed in hypertrophy of the total muscle CSA and fiber areas with no change in estimated fiber number , whereas capillary changes were proportional to muscle fiber growth Strength training represents an alternative to endurance training for patients with type 2 diabetes . Little is known about the effect on insulin action and key proteins in skeletal muscle , and the necessary volume of strength training is unknown . A total of 10 type 2 diabetic subjects and 7 healthy men ( control subjects ) strength-trained one leg three times per week for 6 weeks while the other leg remained untrained . Each session lasted no more than 30 min . After strength training , muscle biopsies were obtained , and an isoglycemic-hyperinsulinemic clamp combined with arterio-femoral venous catheterization of both legs was carried out . In general , qualitatively similar responses were obtained in both groups . During the clamp , leg blood flow was higher ( P < 0.05 ) in trained versus untrained legs , but despite this , arterio-venous extraction glucose did not decrease in trained legs . Thus , leg glucose clearance was increased in trained legs ( P < 0.05 ) and more than explained by increases in muscle mass . Strength training increased protein content of GLUT4 , insulin receptor , protein kinase B-alpha/beta , glycogen synthase ( GS ) , and GS total activity . In conclusion , we found that strength training for 30 min three times per week increases insulin action in skeletal muscle in both groups . The adaptation is attributable to local contraction-mediated mechanisms involving key proteins in the insulin signaling cascade Theoretically , disturbancies in sodium ( Na ) and potassium ( K ) homeostasis and a magnesium ( Mg ) deficit could be possible factors in the development of obesity , type 2 diabetes , and hypertension . Therefore , we measured electrolyte content and [3H]ouabain binding capacity of skeletal muscle in 20 relatives of type 2 diabetic patients and in 20 controls before and after glucose infusion and before and after treatment with dexamethasone , which decreases insulin sensitivity . Muscle electrolyte content and [3H]ouabain binding capacity did not differ between groups . Infusion of glucose increased muscle Na content 25 % , decreased muscle potassium content 9 % , and muscle Mg content 5 % . Muscle potassium/Mg ratio decreased only in relatives . Treatment with dexamethasone increased muscle Na content 15 % and decreased muscle Mg content 7 % , whereas muscle potassium/Na ratio decreased 17 % . Dexamethasone increased muscle [3H]ouabain binding capacity by 42 % in both groups . Basal and 1-hour intramuscular glucose content correlated inversely with basal muscle potassium/Na ratio in relatives only . In conclusion , persons who were predisposed to the development of type 2 diabetes exhibited an increased interdependency between glucose , Na , and potassium h and ling in skeletal muscle . Muscle Na content and [3H]ouabain binding capacity increased during treatment with dexamethasone , and muscle potassium/Na ratio decreased . Intravenous ( IV ) glucose injection decreases muscle Mg content , as does a decrease in insulin sensitivity , without any differences between relatives and controls |
12,996 | 28,825,321 | Conclusions High-intensity interval training may improve peak oxygen uptake and should be considered as a component of care of coronary artery disease patients .
However , this superiority disappeared when isocaloric protocol is compared | Background Exercise is an effective strategy for reducing total and cardiovascular mortality in patients with coronary artery disease .
However , it is not clear which modality is best .
We performed a meta- analysis to investigate the effects of high-intensity interval versus moderate-intensity continuous training of coronary artery disease patients . | The oxygen uptake efficiency slope ( OUES ) is a submaximal index incorporating cardiovascular , peripheral , and pulmonary factors that determine the ventilatory response to exercise . The purpose of this study was to evaluate the effects of continuous exercise training and interval exercise training on the OUES in patients with coronary artery disease . Thirty-five patients ( 59.3±1.8 years old ; 28 men , 7 women ) with coronary artery disease were r and omly divided into two groups : continuous exercise training ( n=18 ) and interval exercise training ( n=17 ) . All patients performed grade d exercise tests with respiratory gas analysis before and 3 months after the exercise-training program to determine ventilatory anaerobic threshold ( VAT ) , respiratory compensation point , and peak oxygen consumption ( peak VO2 ) . The OUES was assessed based on data from the second minute of exercise until exhaustion by calculating the slope of the linear relation between oxygen uptake and the logarithm of total ventilation . After the interventions , both groups showed increased aerobic fitness ( P<0.05 ) . In addition , both the continuous exercise and interval exercise training groups demonstrated an increase in OUES ( P<0.05 ) . Significant associations were observed in both groups : 1 ) continuous exercise training ( OUES and peak VO2 r=0.57 ; OUES and VO2 VAT r=0.57 ) ; 2 ) interval exercise training ( OUES and peak VO2 r=0.80 ; OUES and VO2 VAT r=0.67 ) . Continuous and interval exercise training result ed in a similar increase in OUES among patients with coronary artery disease . These findings suggest that improvements in OUES among CAD patients after aerobic exercise training may be dependent on peripheral and central mechanisms Objective . To study the effect of aerobic treadmill exercise training with different intensity on left ventricular ( LV ) function in patients with stable coronary artery disease , using Strain Rate- and Tissue Doppler Imaging . Design . Seventeen patients were r and omly assigned to either moderate ( 50–60 % of peak oxygen uptake ( VO2peak ) ) or high intensity exercise ( 80–90 % of VO2peak ) for 10 weeks . Results . The increase of VO2peak was significantly higher ( p=0.01 ) in the high intensity group ( 17 vs. 8 % ) . Mean LV early diastolic strain rate increased in the high , but not in the moderate , intensity group . For systolic strain rate or mitral annular velocities there were no change after training in either group . Conclusions . Aerobic treadmill exercise improves early diastolic relaxation in patients with stable coronary artery disease , measured by the mean LV early diastolic strain rate 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 We found that interval training provides an effective means to improve the cardiovascular fitness and health status of highly functional patients with coronary artery disease . We also revealed that interval training improves anaerobic tolerance to a greater extent than the traditional exercise training model without increasing the risk to the patient . This research supports the implementation of interval training for highly functional patients with coronary artery disease BACKGROUND Peak oxygen uptake ( pVO2 ) is used for risk stratification in chronic heart failure ( CHF ) , but little is known about the prognostic impact of pVO2-changes in patients on chronic beta-blocker ( BBL ) therapy . We therefore prospect ively evaluated individual pVO2-changes at a 6-month interval in patients all receiving BBL . METHODS 194 patients with stable CHF on stable medication were included ( V1 ) and underwent clinical evaluation and exercise testing . Testing was repeated ( V2 ) at 5.7+/-1.5 months after V1 and patients were followed > 12 months after V2 . Death or hospitalisation due to cardiac reasons was the predefined EP ( EPP , end-point positive ; n=62 ; EPN , end-point negative ; n=113 ) . RESULTS Initial characteristics did not differ between EPP and EPN . Multivariate cox regression analysis revealed that change of pVO2 ( EPP : -0.6+/-2.6 ml/kg min ; EPN : + 2.5+/-3.3 ml/kg min ; p<0.001 ) was independent to pVO2 , LVEF , NTproBNP and NYHA at V2 for prediction of the combined end-point during follow-up . An increase of pVO2 by 10 % was identified as an adequate cut-off value for risk stratification and ROC- analysis showed the significant incremental prognostic value of the determination of pVO2 changes in combination with pVO2 . CONCLUSIONS Serial measurements of pVO2 yield additional information for risk stratification in clinical ly homogenous CHF patients receiving BBL . This is the first study demonstrating this fact within a narrow predefined interval with all patients on BBL The aim of the present study was to investigate effects of aerobic interval training ( AIT ) versus moderate continuous training ( MCT ) on coronary atherosclerosis in patients with significant coronary artery disease on optimal medical treatment . Thirty-six patients were r and omized to AIT ( intervals at ≈ 90 % of peak heart rate ) or MCT ( continuous exercise at ≈ 70 % of peak heart rate ) 3 times a week for 12 weeks after intracoronary stent implantation . Grayscale and radiofrequency intravascular ultrasounds ( IVUS ) were performed at baseline and follow-up . The primary end point was the change in plaque burden , and the secondary end points were change in necrotic core and plaque vulnerability . Separate lesions were classified using radiofrequency IVUS criteria . We demonstrated that necrotic core was reduced in both groups in defined coronary segments ( AIT -3.2 % , MCT -2.7 % , p < 0.05 ) and in separate lesions ( median change -2.3 % and -0.15 mm(3 ) , p < 0.05 ) . Plaque burden was reduced by 10.7 % in separate lesions independent of intervention group ( p = 0.06 ) . No significant differences in IVUS parameters were found between exercise groups . A minority of separate lesions were transformed in terms of plaque vulnerability during follow-up with large individual differences between and within patients . In conclusion , changes in coronary artery plaque structure or morphology did not differ between patients who underwent AIT or MCT . The combination of regular aerobic exercise and optimal medical treatment for 12 weeks induced a moderate regression of necrotic core and plaque burden in IVUS-defined coronary lesions OBJECTIVE : The purpose of this study was to evaluate the following : 1 ) the effects of continuous exercise training and interval exercise training on the end-tidal carbon dioxide pressure ( PETCO2 ) response during a grade d exercise test in patients with coronary artery disease ; and 2 ) the effects of exercise training modalities on the association between PETCO2 at the ventilatory anaerobic threshold ( VAT ) and indicators of ventilatory efficiency and cardiorespiratory fitness in patients with coronary artery disease . METHODS : Thirty-seven patients ( 59.7±1.7 years ) with coronary artery disease were r and omly divided into two groups : continuous exercise training ( n = 20 ) and interval exercise training ( n = 17 ) . All patients performed a grade d exercise test with respiratory gas analysis before and after three months of the exercise training program to determine the VAT , respiratory compensation point ( RCP ) and peak oxygen consumption . RESULTS : After the interventions , both groups exhibited increased cardiorespiratory fitness . Indeed , the continuous exercise and interval exercise training groups demonstrated increases in both ventilatory efficiency and PETCO2 values at VAT , RCP , and peak of exercise . Significant associations were observed in both groups : 1 ) continuous exercise training ( PETCO2VAT and cardiorespiratory fitness r = 0.49 ; PETCO2VAT and ventilatory efficiency r = -0.80 ) and 2 ) interval exercise training ( PETCO2VAT and cardiorespiratory fitness r = 0.39 ; PETCO2VAT and ventilatory efficiency r = -0.45 ) . CONCLUSIONS : Both exercise training modalities showed similar increases in PETCO2 levels during a grade d exercise test in patients with coronary artery disease , which may be associated with an improvement in ventilatory efficiency and cardiorespiratory fitness Background . We tested the hypothesis that high intensity interval training ( HIIT ) would be more effective than moderate intensity continuous training ( MIT ) to improve newly emerged markers of cardiorespiratory fitness in coronary heart disease ( CHD ) patients , as the relationship between ventilation and carbon dioxide production ( VE/VCO2 slope ) , oxygen uptake efficiency slope ( OUES ) , and oxygen pulse ( O2P ) . Methods . Seventy-one patients with optimized treatment were r and omly assigned into HIIT ( n = 23 , age = 56 ± 12 years ) , MIT ( n = 24 , age = 62 ± 12 years ) , or nonexercise control group ( CG ) ( n = 24 , age = 64 ± 12 years ) . MIT performed 30 min of continuous aerobic exercise at 70–75 % of maximal heart rate ( HRmax ) , and HIIT performed 30 min sessions split in 2 min alternate bouts at 60%/90 % HRmax ( 3 times/week for 16 weeks ) . Results . No differences among groups ( before versus after ) were found for VE/VCO2 slope or OUES ( P > 0.05 ) . After training the O2P slope increased in HIIT ( 22 % , P < 0.05 ) but not in MIT ( 2 % , P > 0.05 ) , while decreased in CG ( −20 % , P < 0.05 ) becoming lower versus HIIT ( P = 0.03 ) . Conclusion . HIIT was more effective than MIT for improving O2P slope in CHD patients , while VE/VCO2 slope and OUES were similarly improved by aerobic training regimens versus controls Objective : Exercise capacity strongly predicts survival and aerobic interval training ( AIT ) increases peak oxygen uptake effectively in cardiac patients . Usual care in Norway provides exercise training at the hospitals following myocardial infa rct ion ( MI ) , but the effect and actual intensity of these rehabilitation programmes are unknown . Design : R and omized controlled trial . Setting : Hospital cardiac rehabilitation . Subjects : One hundred and seven patients , recruited two to 12 weeks after MI , were r and omized to usual care rehabilitation or treadmill AIT . Interventions : Usual care aerobic group exercise training or treadmill AIT as 4 × 4 minutes intervals at 85–95 % of peak heart rate . Twice weekly exercise training for 12 weeks . Main measures : The primary outcome measure was peak oxygen uptake . Secondary outcome measures were endothelial function , blood markers of cardiovascular disease , quality of life , resting heart rate , and heart rate recovery . Results : Eighty-nine patients ( 74 men , 15 women , 57.4 ± 9.5 years ) completed the programme . Peak oxygen uptake increased more ( P = 0.002 ) after AIT ( from 31.6 ± 5.8 to 36.2 ± 8.6 mL·kg−1·min−1 , P < 0.001 ) than after usual care rehabilitation ( from 32.2 ± 6.7 to 34.7 ± 7.9 mL·kg−1·min−1 , P < 0.001 ) . The AIT group exercised with significantly higher intensity in the intervals compared to the highest intensity in the usual care group ( 87.3 ± 3.9 % versus 78.7 ± 7.2 % of peak heart rate , respectively , P < 0.001 ) . Both programmes increased endothelial function , serum adiponectin , and quality of life , and reduced serum ferritin and resting heart rate . High-density lipoprotein cholesterol increased only after AIT . Conclusions : AIT increased peak oxygen uptake more than the usual care rehabilitation provided to MI patients by Norwegian hospitals Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists PURPOSE Isocaloric interval exercise training programs have been shown to elicit improvements in numerous physiological indices in patients with CAD . Low-volume high-intensity interval exercise training ( HIT ) is effective in healthy population s ; however , its effectiveness in cardiac rehabilitation has not been established . This study compared the effects of 12-wk of HIT and higher-volume moderate-intensity endurance exercise ( END ) on brachial artery flow-mediated dilation ( FMD ) and cardiorespiratory fitness ( VO2 peak ) in patients with CAD . METHODS Twenty-two patients with documented CAD were r and omized into HIT ( n = 11 ) or END ( n = 11 ) based on pretraining FMD . Both groups attended two supervised sessions per week for 12 wk . END performed 30 - 50 min of continuous cycling at 58 % peak power output ( PPO ) , whereas HIT performed ten 1-min intervals at 89 % PPO separated by 1-min intervals at 10 % PPO per session . RESULTS Relative FMD was increased posttraining ( END , 4.4 % ± 2.6 % vs 5.9 % ± 3.6 % ; HIT , 4.6 % ± 3.6 % vs 6.1 % ± 3.4 % , P ≤ 0.001 pre- vs posttraining ) with no differences between groups . A training effect was also observed for relative VO2 peak ( END , 18.7 ± 5.7 vs 22.3 ± 6.1 mL · kg(-1 ) · min(-1 ) ; HIT , 19.8 ± 3.7 vs 24.5 ± 4.5 mL · kg(-1 ) · min(-1 ) , P < 0.001 for pre- vs posttraining ) , with no group differences . CONCLUSIONS Low-volume HIT provides an alternative to the current , more time-intensive prescription for cardiac rehabilitation . HIT elicited similar improvements in fitness and FMD as END , despite differences in exercise duration and intensity BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . This document revises and up date s the original “ Guidelines for Coronary Angiography , ” published in 1987 . This executive summary and recommendations appears in the May 4 , 1999 , issue of Circulation . The guidelines in their entirety , including the American College of Cardiology/American Heart Association ( ACC/AHA ) class I , II , and III recommendations , are published in the May 1999 issue of the Journal of the American College of Cardiology . Reprints of both the full text and executive summary and recommendations are available from both organizations . The frequent and still growing use of coronary angiography , its relatively high costs , its inherent risks , and the ongoing evolution of its indications provide the reasons for this revision . The committee appointed to develop this document included private practitioners and academicians who were selected to represent both experts in coronary angiography and senior clinician consultants . Representatives from the family practice and internal medicine professions were also included on the committee . In addition to review ing the original document , the committee conducted a search of the literature for the 10 years preceding development of these guidelines . Evidence was compiled and ranked by the committee . Whereas r and omized trials are often available for reference in the development of treatment guidelines , r and omized trials regarding the use of diagnostic procedures such as coronary angiography are rarely available . This document uses the ACC/AHA classifications of class I , II , and III . These classes summarize the indications for coronary angiography as follows : Class I : Conditions for which there is evidence and /or general agreement that this procedure is useful and effective . Class II : Conditions for which there is conflicting evidence and /or a divergence of opinion about the usefulness/efficacy of performing the procedure . Class IIa : Weight of evidence /opinion is in favor of usefulness/ efficacy . Class IIb : Usefulness/efficacy is less well established by evidence /opinion . Class III : Conditions for which there 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 BACKGROUND Exercise-based cardiac rehabilitation increases peak oxygen uptake ( peak VO₂ ) , which is an important predictor of mortality in cardiac patients . However , it remains unclear which exercise characteristics are most effective for improving peak VO₂ in coronary artery disease ( CAD ) patients . Proof of concept papers comparing Aerobic Interval Training ( AIT ) and Moderate Continuous Training ( MCT ) were conducted in small sample sizes and findings were inconsistent and heterogeneous . Therefore , we aim ed to compare the effects of AIT and Aerobic Continuous Training ( ACT ) on peak VO₂ , peripheral endothelial function , cardiovascular risk factors , quality of life and safety , in a large multicentre study . METHODS Two-hundred CAD patients ( LVEF > 40 % , 90 % men , mean age 58.4 ± 9.1 years ) were r and omized to a supervised 12-week cardiac rehabilitation programme of three weekly sessions of either AIT ( 90 - 95 % of peak heart rate ( HR ) ) or ACT ( 70 - 75 % of peak HR ) on a bicycle . Primary outcome was peak VO₂ ; secondary outcomes were peripheral endothelial function , cardiovascular risk factors , quality of life and safety . RESULTS Peak VO₂ ( ml/kg/min ) increased significantly in both groups ( AIT 22.7 ± 17.6 % versus ACT 20.3 ± 15.3 % ; p-time<0.001 ) . In addition , flow-mediated dilation ( AIT+34.1 % ( range -69.8 to 646 % ) versus ACT+7.14 % ( range -66.7 to 503 % ) ; p-time<0.001 ) quality of life and some other cardiovascular risk factors including resting diastolic blood pressure and HDL-C improved significantly after training . Improvements were equal for both training interventions . CONCLUSIONS Contrary to earlier smaller trials , we observed similar improvements in exercise capacity and peripheral endothelial function following AIT and ACT in a large population of CAD patients PURPOSE : We tested the hypothesis that higher-intensity interval training ( HIIT ) could be deployed into a st and ard cardiac rehabilitation ( CR ) setting and would result in a greater increase in cardiorespiratory fitness ( ie , peak oxygen uptake , ) versus moderate-intensity continuous training ( MCT ) . METHODS : Thirty-nine patients participating in a st and ard phase 2 CR program were r and omized to HIIT or MCT ; 15 patients and 13 patients in the HIIT and MCT groups , respectively , completed CR and baseline and followup cardiopulmonary exercise testing . RESULTS : No patients in either study group experienced an event that required hospitalization during or within 3 hours after exercise . The changes in resting heart rate and blood pressure at followup testing were similar for both HIIT and MCT . at ventilatory-derived anaerobic threshold increased more ( P < .05 ) with HIIT ( 3.0 ± 2.8 mL·kg·−1min−1 ) versus MCT ( 0.7 ± 2.2 mL·kg·−1min−1 ) . During followup testing , submaximal heart rate at the end of stage 2 of the exercise test was significantly lower within both the HIIT and MCT groups , with no difference noted between groups . Peak V˙o2 improved more after CR in patients in HIIT versus MCT ( 3.6 ± 3.1 mL·kg.−1·min−1 vs 1.7 ± 1.7 mL·kg.−1·min−1 ; P < .05 ) . CONCLUSIONS : Among patients with stable coronary heart disease on evidence -based therapy , HIIT was successfully integrated into a st and ard CR setting and , when compared to MCT , result ed in greater improvement in peak exercise capacity and submaximal endurance Background Aerobic interval training ( AIT ) and aerobic continuous training ( ACT ) both improve physical fitness ( peak VO2 ) in coronary artery disease patients . However , little is known about the long-term effects of AIT and ACT on peak VO2 and exercise adherence . Design This study is a r and omized clinical multicenter trial . Methods In total , 163 patients were assessed after 12 weeks of AIT or ACT and 12 months after their enrollment . Physical fitness and physical activity measures served as the primary outcomes , and peripheral endothelial function , cardiovascular risk factors and quality of life ( QoL ) served as the secondary outcomes . Results Twenty-six patients dropped out during the intervention ; 11 were lost during the follow-up period . Dropouts ( n = 37 ) consisted of more women ( p = 0.001 ) compared to completers ( n = 163 ) . Physical fitness ( VO2 , heart rate and workload at peak and at thresholds ) and physical activity ( steps , active energy expenditure [ kcal ] , physical activity duration [ minutes ] ) were preserved at the 1-year follow-up ( p-time > 0.05 ) after both AIT and ACT ( p-interaction > 0.05 ) . Forty percent of patients showed increased peak VO2 , 52 % showed increased active energy expenditure and 91.2 % met the recommended levels of 150 minutes/week of moderate physical activity ( p-group > 0.05 ) . Further , peripheral endothelial function , QoL and cardiovascular risk factors , except systolic blood pressure ( p-time < 0.05 ) , remained stable ( p-time > 0.05 ) after both AIT and ACT ( p-interaction > 0.05 ) . Conclusion The short-term improvements of center-based AIT and ACT on physical fitness , physical activity , peripheral endothelial function , cardiovascular risk factors and QoL are sustained after a 1-year follow-up period . The majority of patients ( > 90 % ) met the recommended physical activity levels of 150 minutes/week |
12,997 | 19,128,927 | Serious adverse events after ELT or surgery were rare .
While occurrence rates of some minor adverse events appeared higher after ELT in collated data , comparative studies commonly favored ELT over surgery .
Few differences were apparent between treatments with respect to clinical effectiveness outcomes , although long-term follow-up was lacking .
Non clinical effectiveness outcomes generally favored ELT over surgery in the first 2 months after treatment .
ELT appears to be at least as safe as surgery . | This systematic review compares the safety and efficacy of endovenous laser therapy ( ELT ) and surgery involving saphenous ligation and stripping as treatments for varicose veins . | PURPOSE We set out to assess the new Aberdeen Varicose Veins Question naire ( Aberdeen Question naire ) for the properties necessary for a valid measure of health outcome , to determine quality of life of patients with varicose veins , and to determine the effect of surgery on quality of life . METHODS A prospect i ve consecutive cohort of 137 patients undergoing varicose vein surgery completed the self-administered SF-36 and Aberdeen Question naire and 25 questions relating to the symptoms and concerns of patients with varicose veins . Follow-up was done by repeated question naires 6 weeks after surgery . The Aberdeen Question naire was assessed for reliability , validity , responsiveness , and practicality . Quality of life of patients with varicose veins was compared with an age- and sex-matched sample of the general population . RESULTS Reliability estimates for the 8 scales short-form health survey ( SF-36 ) and the Aberdeen Question naire were all above 0.7 ( Cronbach 's alpha ) . The Aberdeen Question naire had a highly significant correlation ( r = 0 . 74 , P < .0001 ) with the patients ' symptoms and concerns question naire , which is evidence of its validity . Patients with varicose veins score lower than United Kingdom norms ( P < .001 ) in the physical domains of the SF-36 , indicating worse health . After surgery , the SF-36 scores improved in all 8 domains of health , reaching significance in " Mental Health " ( P < .05 ) and approaching significance in " General Health " ( P = .066 ) . The Health Transition Item of the SF-36 and the Aberdeen Question naire both showed a highly significant improvement in health ( P < .001 ) . CONCLUSION The Aberdeen Question naire is a valid measure of quality of life for patients with varicose veins . Persons with varicose veins have a reduced quality of life compared with the general population , and this discrepancy is significantly improved at 6 weeks by operating on them OBJECTIVE To determine whether a period of one or three weeks of compression following varicose vein surgery influenced the outcome . DESIGN R and omised controlled trial . METHOD 300 patients aged between 18 - 80 years underwent unilateral varicose vein surgery in a Day Procedure Unit . Compression b and aging was applied post-operatively for three days . Patients then wore graduated elastic compression stockings r and omised to a period of either one or three weeks . Patients were assessed by question naire on pain scores at rest and during mobilisation for up to six weeks , total analgesic consumption , duration of time off work , any complications , and patient perception of cosmetic results at various periods up to 12 weeks following surgery . RESULTS The mean pain score reported by patients over 6 weeks was similar in the two groups ( 1 week group : mean 2.18 , three week group : mean 1.87 ) . The 95 % confidence interval ( CI ) for the mean difference in pain was ( -0.05 - 0.66 ) . Analysis of the pain curves at 1 week , 4 weeks and 6 weeks , showed equivalence at 4 and 6 weeks , but not for 1 week , with the group wearing stockings for only one week complaining of more pain for this period . A significant increase in the total number of analgesia tablets consumed was also found in the group wearing stockings for only one week . No significant differences were found in the other secondary endpoints - return to work ( categorised as < 2 weeks , 2 - 6 weeks or 6 - 12 weeks ) , patient satisfaction or post-operative complications . CONCLUSION We found no benefit in wearing compression stockings for more than one week following uncomplicated high saphenous ligation with stripping of the great saphenous vein with respect to post-operative pain , number of complications , time to return to work , or patient satisfaction for up to 12 weeks following surgery Quality of life may be considerably reduced in patients who are suffering from chronic lower limb venous insufficiency , although existing generic quality of life instruments ( NHP , SF-36 or SIP ) can not completely identify their specific complaints . The Chronic Venous Insufficiency Question naire ( CIVIQ ) has been developed by iterative process . First , a pilot group of 20 patients was used to identify a number of important features of quality of life affected by venous insufficiency , other than physical symptoms of discomfort . A second study involving 2,001 subjects was used to reduce the number of items . Subjects were asked to score both the severity of their problems and the importance they attributed to each problem on a 5-point Likert scale . The importance items found in patients with venous insufficiency were subjected to factorial analyses ( PCA , PAF ) . The final version is a 20-item self-administered question naire which explores four dimensions : psychological , physical and social functioning and pain . Internal consistency of the question naire was vali date d for each dimension ( Cronbach 's alpha > 0.820 for three out of four factors ) . Reproducibility was confirmed in a 60 patient test-retest study . Pearson 's correlation coefficients for both the four dimension subscales and for the global score at 2-week intervals were greater than 0.940 . Finally , the question naire was tested in a r and omized clinical trial of 934 patients in order to assess responsiveness and the convergent validity of the instrument , together with the patient 's own quality of life . This study demonstrated that convergence was valid : Pearson 's correlation coefficients between clinical score differences and quality of life score differences were small ( from 0.199–0.564 ) but were statistically different from 0 ( p<0.001 ) . St and ardized response mean ( SRM ) and effect size ( ES ) were calculated to assess sensitivity to change . SRM and ES both demonstrated considerble responsiveness to change ( > 0.80 ) . Reliability , face , content , construct validity and responsiveness were also determined for this specific quality of life question naire relating to venous insufficiency . Results suggest that this question naire may be used with confidence to assess quality of life in clinical trials on chronic venous insufficiency OBJECTIVE --To develop a valid and reliable outcome measure for patients with varicose veins . DESIGN --Postal question naire survey of patients with varicose veins . SETTING --Surgical outpatient departments and training general practice s in Grampian region . SUBJECTS--373 patients , 287 of whom had just been referred to hospital for their varicose veins and 86 who had just consulted a general practitioner for this condition and , for comparison , a r and om sample of 900 members of the general population . MAIN MEASURES --Content validity , internal consistency , and criterion validity . RESULTS --281(76 % ) patients ( mean age 45.8 ; 76 % female ) and 542(60 % ) of the general population ( mean age 47.9 ; 54 % female ) responded . The question naire had good internal consistency as measured by item-total correlations . Factor analysis identified four important health factors : pain and dysfunction , cosmetic appearance , extent of varicosity and complications . The validity of the question naire was demonstrated by a high correlation with the SF-36 health profile , which is a general measure of patients ' health . The perceived health of patients with varicose veins , as measured by the SF-36 , was significantly lower than that of the sample of the general population adjusted for age and a lower proportion of women . CONCLUSION --A clinical ly derived question naire can provide a valid and reliable tool to assess the perceived health of patients with varicose veins . IMPLICATION S -- The question naire may be used to justify surgical treatment of varicose veins BACKGROUND Neoreflux at the sapheno-femoral junction ( SFJ ) is an important cause of recurrent great saphenous varicose veins . This study compares four surgical methods of ligating the SFJ with the aim to reduce the rate of neoreflux . METHOD In a prospect i ve study , 379 patients ( 500 SFJ ligations ) were r and omised to one of four surgical procedures at the SFJ ( 125 groins each ) . In group A ( control group ) the SFJ was ligated in st and ard fashion with Vicryl ( absorbable ligature ) ; in group B , after Vicryl ligation continuous Prolene ( non-absorbable ) was sutured over the stump endothelium to prevent any contact with surrounding tissue ; in group C. SFJ ligation was done with Ethibond ( non-absorbable ) ; in group D Ethibond ligation was followed by Prolene oversewing . The final study group included 114 patients ( 152 groins ) who were all known to be free from recurrent groin reflux 3 months postoperatively and had colour duplex venous imaging 2 years after operation . RESULTS Duplex imaging identified neoreflux at the SFJ in 10 out of 114 groins after 2 years ( 7 % ) . There were differences in the rates between the four groups : Group A 3/31 ( 10 % ) , Group B 0/32 , Group C 5/44 ( 11 % ) and Group D 2/45 ( 4 % ) . Neoreflux was significantly reduced in the two groups with endothelial closure ( B and D ) : 2/70 ( 3 % ) versus 8/75 ( 11 % , p<0.025 ) . CONCLUSION Recurrent reflux in the groin was reduced by over sewing the ligated SFJ in patients having varicose vein surgery . This adds weight to the theory of neovascularisation as a cause of recurrent veins and offers a means to reduce clinical recurrence rates AIM The innovations for disease management need to be thoroughly evaluated so that their benefits and potential downsides can be compared with the already existing approaches . Endovascular laser ( EVL ) treatment for varicose veins offers today several advantages over surgical st and ard stripping . The Italian Endovenous-laser Working Group ( IEWG ) is a homogeneous group of surgeons and phlebologists who have been using EVL since 1999 and has undertaken to examine EVL in a multicenter study starting from a well defined rationale , with the benefit of a single protocol to use . METHODS In a cooperative , multicenter , clinical study , 1076 limbs in 1050 patients , mean age of 54.5 years , 241 males and 809 females affected by chronic venous insufficiency ( CVI ) were considered eligible for surgery and stratified by CEAP classification in a four-year period ( January 1999 December 2003 ) . Inclusion criteria were insufficiency of the great and /or small saphenous vein at various levels , beyond those accessory saphenous trunks with incompetence in the saphenofemoral junction . In all cases truncular reflux apparead up on duplex scan examination , with or without associated varicosities . All the patients underwent a surgery on the basis of the clinical assessment . All the centres involved performed treatment in conformity with the Food and Drug Administration ( FDA ) vali date d procedure , using an endo-laser venous system kit with a 810 - 980 nm diode . Duplex scan was performed in all patients after 36 months with very few lost to follow-up cases . RESULTS In the immediate postoperative period the results have been impressive , with a very effective closure of incompetent great saphenous vein and the other treated varicose veins ( the early occlusion rate has been 99 % ) . Major complications have not been detected : in particular , no deep venous thrombosis ( DVT ) evaluated duplex ultrasound . The patients ' acceptability and satisfaction regarding the procedure , have been measured by means of a question naire on the quality of life , and the result was 96.7 % . After 36 months , the total occusion rate of saphenous trunks has been 97 % . CONCLUSIONS The first important Italian experience with EVL based on preoperative , perioperative and postoperative duplex control and which is also based on the patients ' satisfaction at mid/long-term has indicated some advantages over the st and ard treatment with the stripping method . In terms of reduced postoperative pain , shorter sick leave , a faster resumption of the normal activities , and , in particular , the total absence of DVT , we can conclude that EVL is a good solution for all patients with anatomic and hemodinamic patterns for saphenous vein surgery 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 OBJECTIVE Conventional surgery for varicose veins due to small saphenous reflux is associated with high recurrence rates ( up to 50 % ) , many result ing from inadequate surgery . This prospect i ve audit examines the safety and efficacy of EVLA in the treatment of this . METHOD 65 patients ( 68 limbs ) with varicosities due to primary or recurrent sapheno-popliteal junction ( SPJ ) and small saphenous vein ( SSV ) reflux underwent out-patient EVLA ( 810 nm diode laser ) . The SSV was ablated from mid-calf to the SPJ . Symptomatic improvement ( Aberdeen Varicose Vein Severity Score [ AVVSS ] ) , time to return to normal activity , post-EVLA analgesic requirements , and complications were recorded . RESULTS Duplex ultrasound follow-up ( median 6-months ) confirmed abolition of SPJ/SSV reflux in all limbs following a median total laser energy delivery of 1131J ( IQR 928 - 1364 ) at an energy density of 66.3 Joules/cm ( IQR 54.2 - 71.6 ) . AVVSS improved from 15.4 ( IQR 11.8 - 19.7 ) to 4.6 ( IQR 3.2 - 6.7 ) at three months ( p<0.001 ) . Median analgesia requirement was 3 days ( 23 % [ 15/65 ] patients required none ) and the median time to normal activity was 0 ( 0 - 4 ) days ( 65 % [ 42/65 ] returning to normal daily activity immediately ) . There were no instances of skin burns or DVT but 3 patients ( 4.4 % ) developed transient cutaneous numbness ( sural nerve ) . 98 % ( 64/65 ) patients would undergo EVLT again . CONCLUSIONS EVLA abolished SPJ/SSV reflux in all limbs . This is likely to be more effective than conventional surgery , although long-term follow up is required . Data from a r and omised control trial would be desirable 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 OBJECTIVE The objective of this r and omized , prospect i ve , blinded study was to determine the relative effects of two laser wavelengths in the treatment of great saphenous vein ( GSV ) insufficiency . METHODS Fifty-one male and female patients scheduled for routine laser treatment of GSV insufficiency provided signed informed consent for the procedure . Patients were r and omized to receive endovenous laser treatment with a wavelength of 810 or 980 nm . The same surgeon , blinded to the wavelength , performed all procedures . Nonoperating study staff , blinded to the laser wavelengths , evaluated patients before and after the procedure regarding physical signs and symptoms . Patients were monitored within 72 hours after the procedure ( via duplex ultrasonography ) , at 1 week ( by procedural site photos scored for bruising , as well as a pain score ) , at 3 weeks , and at 4 months for bruising , physical and emotional effects of the procedure ( scored by patients on a five-point visual analogue scale ) , and symptoms ( scored by the physician ) , along with adverse events . Patients were followed up for a year to determine the long-term efficacy of the procedure . RESULTS The 51 patients ( 38 women and 13 men ; mean age , 52.4 + /- 11.7 years ) completed treatment and follow-up examination ( 30 legs for each wavelength ) . At 72 hours after the procedure , no significant differences were noted between patient outcomes , physical conditions , and symptoms and or possible adverse events . At 1 week after the procedure , bruising scores were significantly different ( P < .005 ) : patients in the 980-nm group showed less bruising of the procedure site than the patients in the 810-nm group . Only three physical or symptom parameters presented with significant differences ( P < .05 ) over time-less itching was noted by 810 nm-treated patients at 3 weeks after the procedure , lower levels of pain intensity were seen in the 980 nm-treated patients at the 4-month follow-up visit , and lower varicose vein ratings were seen for the 980 nm-treated patients at the 4-month follow-up visit . Thirteen legs were phlebitic at 7 days after the procedure ( 10 in the 810-nm group and 3 in the 980-nm group ) . Two treatment failures occurred ( one patient in each treatment group ) ; both patients exhibited flow in the treated venous segment at the 4-month follow-up visit . Two other patients ( one in each group ) had treatment failure at the 1-year follow-up , demonstrating venous insufficiency in the treated segment . CONCLUSIONS Both laser wavelengths were effective in treating GSV insufficiency , with no major complications and a paucity of adverse outcomes Endovenous laser therapy ( EVLT ) is a minimally invasive treatment for varicose veins . This study compares early quality -of-life ( QoL ) outcomes following EVLT and surgery . Two nonr and omized groups were studied : an EVLT group with 70 patients , median age 49 ( interquartile range [ IQR ] 35 - 58 ) years , and a surgery group with 62 patients , median age 49 ( IQR 35 - 61 ) years . Patients were assessed prior to and at 1 , 6 , and 12 weeks following the procedure using the Short Form 36 ( SF-36 ) , the Aberdeen Varicose Veins Question naire ( AVVQ ) , and the Venous Clinical Severity Score ( VCSS ) . Follow-up at 1 , 6 , and 12 weeks was 100 % , 77 % , and 70 % following EVLT and 100 % , 85 % , and 47 % following surgery . SF-36 scores were significantly better in the EVLT group at 1 week ( Physical Functioning , Role Physical , Bodily Pain , Vitality , and Social Functioning domains ) and at 6 weeks ( Physical Functioning and Role Physical ) . At 12 weeks , no significant differences were evident between the groups . AVVQ scores were significantly better in the EVLT group at 6 and 12 weeks . VCSS scores were significantly improved in both groups at 12 weeks . EVLT and surgery provide similar QoL improvements in patients with varicose veins . EVLT , however , removes the QoL limitations experienced by patients in the early postoperative period BACKGROUND Endovenous laser ( EVL ) ablation of the great saphenous vein ( GSV ) is thought to minimize postoperative morbidity and reduce work loss compared with high ligation and stripping ( HL/S ) . However , the procedures have not previously been compared in a r and omized trial with parallel groups where both treatments were performed in tumescent anesthesia on an out-patient basis . METHODS Patients with varicose veins due to GSV insufficiency were r and omized to either EVL ( 980 nm ) or HL/S in tumescent anesthesia . Miniphlebectomies were also performed . Patients were examined preoperatively and at 12 days , and 1 , 3 , and 6 months postoperatively . Sick leave , time to normal physical activity , pain score , use of analgesics , Aberdeen score , Medical Outcomes Study Short Form-36 quality -of-life score , Venous Clinical Severity Score ( VCSS ) , and complication rates were investigated . The total cost of the procedures , including lost wages and equipment , was calculated . Cost calculations were based on the st and ard fee for HL/S with the addition of laser equipment and the st and ard salary and productivity level in Denmark . RESULTS A follow-up of 6 months was achieved in 121 patients ( 137 legs ) . The groups were well matched for patient and GSV characteristics . Two HL/S procedures failed , and three GSVs recanalized in the EVL group . The groups experienced similar improvement in quality -of-life scores and VCSS score at 3 months . Only one patient in the HL/S group had a major complication , a wound infection that was treated successfully with antibiotics . The HL/S and EVL groups did not differ in mean time to resume normal physical activity ( 7.7 vs 6.9 calendar days ) and work ( 7.6 vs 7.0 calendar days ) . Postoperative pain and bruising was higher in the HL/S group , but no difference in the use of analgesics was recorded . The total cost of the procedures , including lost wages , was euro 3084 ( $ 3948 US ) in the HL/S and euro 3396 ( $ 4347 US ) in the EVL group . CONCLUSIONS This study suggests that the short-term efficacy and safety of EVL and HL/S are similar . Except for slightly increased postoperative pain and bruising in the HL/S group , no differences were found between the two treatment modalities . The treatments were equally safe and efficient in eliminating GSV reflux , alleviating symptoms and signs of GSV varicosities , and improving quality of life . Long-term outcomes , particularly with respect to recurrence rates , shall be investigated in future studies , including the continuation of the present OBJECTIVES To observe the effect of local anaesthetic flush through the great saphenous vein ( GSV ) tunnel on postoperative pain and haematoma formation following saphenous vein stripping operations . DESIGN Prospect i ve , double-blind , r and omised , control trial . METHODS One hundred patients were r and omized to receive 20 ml of local anaesthetic ( bupivacaine 0.25 % + adrenaline ) or saline control flush through the GSV tunnel after stripping in a double-blind study . Visual analogue pain scores were used to measure postoperative pain daily for the 1st week , then at 3 weeks and 6 weeks . Patients were examined during the 1st , 3rd and 6th week for haematoma formation . RESULTS In the control group the median postoperative pain score was 4 ( range 0 - 7 ) in the immediate postoperative period compared to a median of 1 ( range 0 - 4 ) in the LA group ( p<0.001 ) . The median pain score on day-4 was 4 ( range 1 - 6 ) ( control ) vs. 1 ( range 0 - 3 ) ( LA group ) ( p<0.001 , Mann-Whitney Utest ) and on day-6 it was 1 ( range 0 - 5 ) ( control ) vs. 0 ( range 0 - 5 ) ( LA group ) ( p<0.001 , Mann-Whitney ) . Twelve patients ( 24 % ) developed a haematoma in the GSV tunnel in the control group compared to three patients ( 6 % ) in the LA group ( p = 0.007 ) . CONCLUSION Flushing of the GSV tunnel with bupivacaine plus adrenaline significantly reduces postoperative pain and haematoma formation in patients undergoing GSV stripping for varicose veins BACKGROUND There are two different ways to operate on patients with varicose veins . OBJECTIVES Prospect i ve evaluation of two groups of patients operated on in two different ways to find out more convenient procedure for varicose veins surgery . METHODS The results of 577 patients operated on for lower limbs varicose veins were evaluated . The patients were divided into two groups . The first group comprised of 125 patients in whom limited stripping of vena saphena magna was performed . The second group comprised of 397 patients in whom total stripping of vena saphena magna was applied . In the remaining 55 patients an operation other than VSM was performed in the venous system of lower limbs . During the follow-up three months after the operation the main attention was paid to a possible neurological disturbance . RESULTS Much better results were observed in the group of patients treated with the method of limited stripping . Neurological disturbances occurred in two patients only ( i.e. 1.6 % ) . Within the other group disturbances were encountered in 28 patients ( i.e. 7 % ) . CONCLUSIONS Limited stripping of vena saphena magna results in lower number of neurological disturbances . ( Tab . 1 , Ref . 10 . ) Varicose vein surgery is generally considered to have little risk of postoperative deep vein thrombosis ( DVT ) . This prospect i ve study examined the incidence of DVT in patients undergoing varicose vein surgery Purpose : To report the 2-year single-center results of endovenous laser treatment ( EVLT ) for reflux in the great saphenous vein ( GSV ) . Methods : From January 2002 to January 2003 , 85 symptomatic patients ( 56 women ; mean age 49 years , range 27–80 ) underwent EVLT in 100 limbs . All patients were symptomatic , and the majority ( 67 , 79 % ) had CEAP clinical class C2 venous disease . After treatment , they were monitored by clinical evaluation and duplex imaging . Results : The initial treatment was completed in 93 limbs . Complications consisted of bruising ( 31 % ) , tightness ( 17 % ) , pain ( 14 % ) , in duration ( 2 % ) , and superficial thrombophlebitis ( 2 % ) . No severe complications were observed . Over a mean follow-up of 29 months ( range 24–37 ) , 3 patients died and 14 were lost to follow-up , leaving 88 ( 95 % ) and 76 ( 82 % ) limbs available for imaging surveillance at 1 and 2 years , respectively . At 3 months , treatment was anatomically successful in 84 % of cases ( 78 complete occlusion , 7 partial occlusion , and 8 nonocclusion ) and functionally successful in 89 % ( 83 no reflux , 10 reflux ) . All technical failures and 73 % ( n=11 ) of the treatment failures occurred in the first half of the studied population , indicating a learning curve effect ( p=0.015 ) . Mean energy delivered per unit length was 39±8 J/cm ( range 25–65 ) for successful treatment ( n=78 ) and 30±10 J/cm ( range 21–50 ) for failed treatment ( n=15 ) . No recanalization or recurrent GSV reflux after anatomically and functionally successful treatment was observed in 73 and 61 limbs at 1 and 2-year follow-up , respectively . Conclusions : EVLT is a feasible , safe , and fast procedure for eliminating GSV reflux and has excellent cosmetic results . Despite the learning curve , we believe that the treatment results are promising . When successful treatment is achieved by EVLT , a prospect i ve follow-up of 2 years demonstrates durable results PURPOSE In this study , the hypothesis that higher energy dose improves procedural success without increasing complications was prospect ively evaluated by performing endovenous laser therapy ( ELT ) at energies greater than 80 J/cm . MATERIAL S AND METHODS One hundred consecutive great saphenous ( GSV ) , anterior accessory great saphenous ( AAGSV ) , or posterior accessory great saphenous ( PAGSV ) veins were treated with the intent to deliver an energy dose of greater than 80 J/cm . Eighty-one patients ( 64 women , 17 men ) were treated . Mean age was 49 years ( range , 25 - 77 years ; SD , 12 years ) . Ultrasound ( US ) and clinical follow-up was performed at 1 week , 3 , 6 , 9 , and 12 months until all veins had at least 3 months of follow-up . Success was defined as absence of reflux throughout the entire treated segment on follow-up US and clinical resolution of symptoms . Incomplete vein ablation was defined as US evidence of flow in a segment of a treated vein at any point during the follow-up period . RESULTS One hundred veins were treated with an average energy of 95 J/cm ( range , 57 - 145 J/cm ; SD , 16 J/cm ) . Follow-up and success at 1 week was 100 % . Four veins could not be followed up beyond 1 week . Of the 96 remaining veins all had 3 months follow-up with an average follow-up of 9 months ( range , 3 - 13 months ; SD , 4 months ) . There were five failures and 91 successes for a success rate of 95 % . Four of the treatment successes demonstrated segmental patency but no reflux on US for a complete vein ablation rate of 91 % . No major complications occurred . The treatment failures occurred at an average energy dose of 98 J/cm . Two of the three failures were AAGSVs , one was a GSV ipsilateral to one of the failed AAGSVs , and two were bilateral GSVs treated during the same procedure . Average body mass index ( BMI ) was 30 for the successes and 46 for the failures . This difference was statistically significant ( P = .0009 ) . The mean length of the failed treatments from the saphenofemoral junction to their termination into a varicose tributary was 10.9 ( range , 8 - 15 cm ; SD , 3.7 cm ) . This was significantly less than the length of the successful treatments ( P = .000003 ) . CONCLUSION Higher energy GSV ELT is safe and highly successful PURPOSE Early and midterm results of endovenous laser treatment ( EVLT ) of the saphenous veins for the treatment of symptomatic insufficiency are promising . However , technical factors contributing to success or failure of saphenous vein EVLT have not been fully investigated . This study was performed to test the hypothesis that treatment success is related to achieving a critical threshold of energy delivery relative to the length of vein treated . MATERIAL S AND METHODS Data regarding length of treated vein and total energy delivered were collected from prospect ively acquired data bases at two institutions . Ultrasound ( US ) examinations were obtained for all treated veins . Successful EVLT was defined as US-documented absence of flow in the treated vein . EVLT failure was defined by US evidence of flow at any point in the treated vein segment at any time more than 1 week after the treatment date . A two-tailed Student t test was performed for statistical analysis and the null hypothesis was rejected at a P value less than .05 . RESULTS One hundred eleven treated veins were followed up with US over 3 - 78 weeks ( mean , 29.5 weeks ) . During this time , 85 treated veins ( 77.5 % ) remained closed . In this group of successfully treated veins , average energy delivered was 63.4 J/cm ( range , 20.5 - 137.8 J/cm ) . The average energy delivered to the 26 veins ( 22.5 % ) in the failure group was 46.6 J/cm ( range , 25.7 - 78 J/cm ) . This difference in delivered energy was statistically significant ( P < .0001 ) . No treatment failures were identified in patients who received doses of 80 J/cm or more . CONCLUSION EVLT is an effective method of incompetent saphenous vein treatment . Greater doses of energy delivered are associated with successful EVLT , particularly when doses of more than 80 J/cm are delivered BACKGROUND Recent reports indicated a correlation between the amount of energy released during endovenous laser treatment ( ELT ) of the great saphenous vein ( GSV ) and the success and durability of the procedure . Our objective was to analyze the influence of increased energy dosing on immediate occlusion and recanalization rates after ELT of the GSV . METHODS GSVs were treated with either 15 or 30 W of laser power by using a 940-nm diode laser with continuous fiber pullback and tumescent local anesthesia . Patients were followed up prospect ively with duplex ultrasonography at day 1 and at 1 , 3 , 6 , and 12 months . RESULTS A total of 114 GSVs were treated with 15 W , and 149 GSVs were treated with 30 W. The average endovenous fluence equivalents were 12.8 + /- 5.1 J/cm2 and 35.1 + /- 15.6 J/cm2 , respectively . GSV occlusion rates according to the method of Kaplan and Meier for the 15- and 30-W groups were 95.6 % and 100 % , respectively , at day 1 , 90.4 % and 100 % at 3 months , and 82.7 % and 97.0 % at 12 months after ELT ( log-rank ; P = .001 ) . An endovenous fluence equivalent exceeding 20 J/cm2 was associated with durable GSV occlusion after 12 months ' follow-up , thus suggesting a schedule for dosing of laser energy with respect to the vein diameter . CONCLUSIONS Higher dosing of laser energy shows a 100 % immediate success rate and a significantly reduced recanalization rate during 12 months ' follow-up PURPOSE To investigate the efficacy of lower-energy endovenous laser treatment for great saphenous vein ( GSV ) incompetence and treatment parameters associated with early treatment failure . MATERIAL S AND METHODS Sixty consecutive endovenous laser treatments ( 32 left , 28 right ; 57 initial treatments , three repeat treatments ) in 48 patients ( 13 men , 35 women ; mean age , 55.2 + /- 12.9 years ) , with bilateral treatments in nine patients , were studied . Preprocedural clinical signs , etiology , anatomy , and physiologic classifications demonstrated class 2 limbs in 11.7 % of cases , class 3 limbs in 25.0 % , class 4 limbs in 48.3 % , and class 5 limbs in 15.0 % . All initial and repeat treatments were performed with lower-energy with use of a 980-nm diode endovenous laser at 11 W in continuous mode . Patients wore class II compression stockings for 2 weeks and were followed up at 1 , 3 , and 6 months with clinical and duplex ultrasound examinations . Treatment failures were diagnosed at 3 months on the basis of GSV patency or lack of clinical improvement . Diameter and length of GSV treated , treatment energy parameters , and clinical outcomes were prospect ively measured and compared between successful and failed treatments . RESULTS The initial treatment success rate was 94.7 % ( 54 of 57 ) . The mean maximum diameter of successfully treated GSVs was 1.12 + /- 0.52 cm , and the mean maximum diameter of GSVs in which treatment failure occurred was 2.05 + /- 0.23 cm ( P = .008 ) . Mean total energy applied for successful treatments was 1,131.3 + /- 248.1 J , and mean total energy applied for failed treatments was 1,439.6 + /- 425.0 J ( P = 0.053 ) . Mean unit energy applied for successful treatments was 32.7 + /- 7.5 J/cm , and that for failed treatments was 32.8 + /- 4.9 J/cm ( P = .986 ) . All patients in whom treatment failed were successfully treated again with a mean total energy of 1,393.0 + /- 81.0 J and a mean unit energy of 29.4 + /- 4.9 J/cm . There were no significant differences in mean total energy or unit energy applied among successful , failed , and repeat treatments ( P > .05 ) . Mean follow-up duration was 6.8 months . CONCLUSIONS Endovenous laser treatment with lower energy appears to be safe and effective . Larger GSV diameter is associated with early treatment failures OBJECTIVE Sclerotherapy ( IS ) or ambulatory phlebectomy ( AP ) are required as subsequent interventions in majority of cases following endovenous laser therapy ( EVLT ) . We assessed whether AP performed concomitantly with EVLT ( EVLTAP ) , is effective , acceptable , and reduces subsequent requirement for interventions . METHOD 67 patients ( 70 limbs ) with great saphenous varicosities underwent EVLTAP . Pain was assessed on days 1 , 4 and 7 using a visual analogue scale ( VAS ) of 0 to 10 . Clinical and ultrasound assessment s were done at 1 , 6 and 12 weeks ( no ultrasound at 6 weeks ) . Residual varicosities underwent further AP or IS . Patients ' satisfaction with the cosmetic outcome and overall treatment was assessed at 12 weeks using a VAS rating . RESULTS 49 patients ( 70 % ) completed follow-up . Median pain scores were 1.6 ( IQR 0.2 - 4.8 ) , 0.3 ( 0 - 1.4 ) and 0.2 ( 0 - 1.1 ) on days 1 , 4 and 7 respectively . Ultrasound demonstrated 69 ( 99 % ) and 47 ( 96 % ) occluded long saphenous veins at 1 and 12 weeks respectively . Subsequent IS or AP was performed on 3 ( 4 % ) or 1 ( 1 % ) limbs respectively . Cosmetic satisfaction was 9.6 ( IQR 8.9 - 10 ) and overall satisfaction 9.8 ( IQR 9.3 - 10 ) . CONCLUSION EVLTAP produces excellent results , is feasible and acceptable , and obviates need for subsequent procedures in the short-term |
12,998 | 27,611,729 | The magnetic technique for SLNB is non-inferior to the st and ard technique , with a high identification rate but with a significantly higher lymph node retrieval rate | BACKGROUND The st and ard for sentinel lymph node biopsy ( SLNB ) , the dual technique ( radiolabelled tracer and blue dye ) , has several drawbacks .
A novel magnetic technique without these drawbacks has been evaluated in a number of clinical trials .
It uses a magnetic tracer and a h and held magnetometer to identify and excise sentinel lymph nodes .
A systematic review and meta- analysis was performed to assess the performance and utility of the magnetic in comparison to the st and ard technique . | Sentinel lymph node biopsy ( SLNB ) is the st and ard surgical procedure for the axilla in early node-negative breast cancer . To date , the " gold st and ard " to localize the sentinel lymph node ( SLN ) is the radiotracer (99m)Tc with or without blue dye . The aim of this study was to evaluate potential equivalency of the new SentiMag ( ® ) technique in comparison to the " gold st and ard " . Within this prospect i ve , multicentric and multinational non-inferiority study including 150 patients (99m)Tc was compared with the magnetic technique , using superparamagnetic iron oxide particles ( SPIOs , Sienna+ ( ® ) ) for localization of SLNs . The results showed a detection rate per patient of 97.3 % ( 146/150 ) for (99m)Tc vs. 98.0 % ( 147/150 ) for Sienna+ ( ® ) with a similar average number of removed SLNs per patient and a higher per patient malignancy detection rate for the SPIO tracer . We obtained convincing results that magnetic SLNB can be performed easily , safely and equivalently well in comparison to the radiotracer method Background Sentinel lymph node biopsy ( SLNB ) in melanoma is currently performed using the st and ard dual technique ( radioisotope and blue dye ) . The magnetic technique is non-radioactive and provides a brown color change in the sentinel lymph node ( SLN ) through an intradermal injection of a magnetic tracer , and utilizes a h and held magnetometer . The MELAMAG Trial compared the magnetic technique with the st and ard technique for SLNB in melanoma . Methods Clinical ly node-negative patients with primary cutaneous melanoma were recruited from four centers . SLNB was undertaken after intradermal administration of both the st and ard ( blue dye and radioisotope ) and magnetic tracers . The SLN identification rate per patient , with the two techniques , was compared . Results A total of 133 patients were recruited , 129 of which were available for final analysis . The sentinel node identification rate was 97.7 % ( 126/129 ) with the st and ard technique and 95.3 % ( 123/129 ) with the magnetic technique [ 2.3 % difference ; 95 % upper confidence limit ( CL ) 6.4 ; 5.4 % discordance ] . With radioisotope alone , the SLN identification rate was 95.3 % ( 123/129 ) , as with the magnetic technique ( 0 % difference ; 95 % upper CL 4.5 ; 7.8 % discordance ) . The lymph node retrieval rate was 1.99 nodes per patient overall , 1.78 with the st and ard technique and 1.87 with the magnetic technique . Conclusions The magnetic technique is feasible for SLNB in melanoma with a high SLN identification rate , but is associated with skin staining . When compared with the st and ard dual technique , it did not reach our predefined non-inferiority margin BACKGROUND AND OBJECTIVES The French Sentimag feasibility trial evaluated a new method for the localization of breast cancer sentinel lymph node ( SLN ) using Sienna+ ® , superparamagnetic iron oxide particles , and Sentimag ® detection in comparison to the st and ard technique ( isotopes ± blue dye ) . METHODS We conducted a prospect i ve multicentric paired comparison trial on 115 patients . SLN localization was performed using both the magnetic technique and the st and ard method . Detection rate and concordance between magnetic and st and ard tracers were calculated . Post-operative complications were assessed after 30 days . RESULTS Results are based on 108 patients . SLN identification rate was 98.1 % [ 93.5 - 99.8 ] for both methods , 97.2 % [ 92.1 - 99.4 ] for Sienna+ ® and 95.4 % [ 89.5 - 98.5 ] for st and ard technique . A mean of 2.1 SLNs per patient was removed . The concordance rate was 99.0 % [ 94.7 - 100.0 % ] per patient and 97.4 % [ 94.1 - 99.2 ] per node . Forty-six patients ( 43.4 % ) had nodal involvement . Among involved SLNs , concordance rate was 97.7 % [ 88.0 - 99.9 ] per patient and 98.1 % [ 90.1 - 100.0 ] per node . CONCLUSIONS This new magnetic tracer is a feasible method and a promising alternative to the isotope . It could offer benefits for ambulatory surgery or sites without nuclear medicine departments . J. Surg . Oncol . 2016;113:501 - 507 . © 2016 Wiley Periodicals , Background The r and omized EORTC 10981 - 22023 AMAROS trial investigates whether breast cancer patients with a tumor-positive sentinel node biopsy ( SNB ) are best treated with an axillary lymph node dissection ( ALND ) or axillary radiotherapy ( ART ) . The aim of the current sub study was to evaluate the identification rate and the nodal involvement . Methods The first 2,000 patients participating in the AMAROS trial were evaluated . Associations between the identification rate and technical , patient- , and tumor-related factors were evaluated . The outcome of the SNB procedure and potential further nodal involvement was assessed . Results In 65 patients , the sentinel node could not be identified . As a result , the sentinel node identification rate was 97 % ( 1,888 of 1,953 ) . Variables affecting the success rate were age , pathological tumor size , histology , year of accrual , and method of detection . The SNB results of 65 % of the patients ( n = 1,220 ) were negative and the patients underwent no further axillary treatment . The SNB results were positive in 34 % of the patients ( n = 647 ) , including macrometastases ( n = 409 , 63 % ) , micrometastases ( n = 161 , 25 % ) , and isolated tumor cells ( n = 77 , 12 % ) . Further nodal involvement in patients with macrometastases , micrometastases , and isolated tumor cells undergoing an ALND was 41 , 18 , and 18 % , respectively . Conclusions With a 97 % detection rate in this prospect i ve international multicenter study , the SNB procedure is highly effective , especially when the combined method is used . Further nodal involvement in patients with micrometastases and isolated tumor cells in the sentinel node was similar — both were 18 % BACKGROUND Sentinel lymph node biopsy in women with operable breast cancer is routinely used in some countries for staging the axilla despite limited data from r and omized trials on morbidity and mortality outcomes . We conducted a multicenter r and omized trial to compare quality -of-life outcomes between patients with clinical ly node-negative invasive breast cancer who received sentinel lymph node biopsy and patients who received st and ard axillary treatment . METHODS The primary outcome measures were arm and shoulder morbidity and quality of life . From November 1999 to October 2003 , 1031 patients were r and omly assigned to undergo sentinel lymph node biopsy ( n = 515 ) or st and ard axillary surgery ( n = 516 ) . Patients with sentinel lymph node metastases proceeded to delayed axillary clearance or received axillary radiotherapy ( depending on the protocol at the treating institution ) . Intention-to-treat analyses of data at 1 , 3 , 6 , and 12 months after surgery are presented . All statistical tests were two-sided . RESULTS The relative risks of any lymphedema and sensory loss for the sentinel lymph node biopsy group compared with the st and ard axillary treatment group at 12 months were 0.37 ( 95 % confidence interval [ CI ] = 0.23 to 0.60 ; absolute rates : 5 % versus 13 % ) and 0.37 ( 95 % CI = 0.27 to 0.50 ; absolute rates : 11 % versus 31 % ) , respectively . Drain usage , length of hospital stay , and time to resumption of normal day-to-day activities after surgery were statistically significantly lower in the sentinel lymph node biopsy group ( all P < .001 ) , and axillary operative time was reduced ( P = .055 ) . Overall patient-recorded quality of life and arm functioning scores were statistically significantly better in the sentinel lymph node biopsy group throughout ( all P < or = .003 ) . These benefits were seen with no increase in anxiety levels in the sentinel lymph node biopsy group ( P > .05 ) . CONCLUSION Sentinel lymph node biopsy is associated with reduced arm morbidity and better quality of life than st and ard axillary treatment and should be the treatment of choice for patients who have early-stage breast cancer with clinical ly negative nodes A mini-symposium was held in Montreal , Canada , at the International Surgical Week for the Breast Surgical International in 2007 addressing the question whether breast cancer is the same disease in Asian and Western countries . Numerous investigators from Asian and Western countries presented the epidemiologic and clinical outcome data of women with breast cancer . Although there are significant similarities , the striking difference is that the peak age for breast cancer is between 40 and 50 years in the Asian countries , whereas the peak age in the Western countries is between 60 and 70 years . Also , the incidence of breast cancer in Asia is rising and is associated with increased mortality . In the West , although the incidence is increasing , the mortality rate is definitely decreasing . Future prospect i ve data collection from Asian and Western countries may provide further interesting epidemiologic and outcome data regarding the outcome of women with breast cancer from Asian and Western countries . Background Whether breast cancer is the same disease in Asian and Western countries was the topic of a 2007 Breast Surgery International symposium at International Surgical Week . Methods Participating investigators from China , Taiwan , India , Japan , South Korea , Sweden , Canada , and the United States were asked beforeh and to provide data on the epidemiology and treatment outcome of women in their countries . Results Comparisons of the epidemiologic and clinical outcome data of women with breast cancer showed significant similarities , but the striking difference is that the peak age is between 40 and 50 years in Asian countries , but is between 60 and 70 years in Western countries . The incidence of breast cancer in Asia is rising and is associated with increased mortality . In the West , although the incidence is also increasing , the mortality rate is definitely decreasing . Discussion Future prospect i ve data collection from Asian and Western countries may provide further interesting epidemiologic and outcome data regarding the outcome of women with breast cancer from Asian and Western countries Background [99mTc]Tilmanocept is a CD206 receptor-targeted radiopharmaceutical design ed for sentinel lymph node ( SLN ) identification . Two nearly identical nonr and omized phase III trials compared [99mTc]tilmanocept to vital blue dye . Methods Patients received [99mTc]tilmanocept and blue dye . SLNs identified intraoperatively as radioactive and /or blue were excised and histologically examined . The primary end point , concordance , was the proportion of blue nodes detected by [99mTc]tilmanocept ; 90 % concordance was the prespecified minimum concordance level . Reverse concordance , the proportion of radioactive nodes detected by blue dye , was also calculated . The prospect i ve statistical plan combined the data from both trials . Results Fifteen centers contributed 154 melanoma patients who were injected with both agents and were intraoperatively evaluated . Intraoperatively , 232 of 235 blue nodes were detected by [99mTc]tilmanocept , for 98.7 % concordance ( p < 0.001 ) . [99mTc]Tilmanocept detected 364 nodes , for 63.7 % reverse concordance ( 232 of 364 nodes ) . [99mTc]Tilmanocept detected at least one node in more patients ( n = 150 ) than blue dye ( n = 138 , p = 0.002 ) . In 135 of 138 patients with at least one blue node , all blue nodes were radioactive . Melanoma was identified in the SLNs of 22.1 % of patients ; all 45 melanoma-positive SLNs were detected by [99mTc]tilmanocept , whereas blue dye detected only 36 ( 80 % ) of 45 ( p = 0.004 ) . No positive SLNs were detected exclusively by blue dye . Four of 34 node-positive patients were identified only by [99mTc]tilmanocept , so 4 ( 2.6 % ) of 154 patients were correctly staged only by [99mTc]tilmanocept . No serious adverse events were attributed to [99mTc]tilmanocept . Conclusions [99mTc]Tilmanocept met the prespecified concordance primary end point , identifying 98.7 % of blue nodes . It identified more SLNs in more patients , and identified more melanoma-containing nodes than blue dye Background The SentiMAG Multicentre Trial evaluated a new magnetic technique for sentinel lymph node biopsy ( SLNB ) against the st and ard ( radioisotope and blue dye or radioisotope alone ) . The magnetic technique does not use radiation and provides both a color change ( brown dye ) and a h and held probe for node localization . The primary end point of this trial was defined as the proportion of sentinel nodes detected with each technique ( identification rate ) . Methods A total of 160 women with breast cancer scheduled for SLNB , who were clinical ly and radiologically node negative , were recruited from seven centers in the United Kingdom and The Netherl and s. SLNB was undertaken after administration of both the magnetic and st and ard tracers ( radioisotope with or without blue dye ) . Results A total of 170 SLNB procedures were undertaken on 161 patients , and 1 patient was excluded , leaving 160 patients for further analysis . The identification rate was 95.0 % ( 152 of 160 ) with the st and ard technique and 94.4 % ( 151 of 160 ) with the magnetic technique ( 0.6 % difference ; 95 % upper confidence limit 4.4 % ; 6.9 % discordance ) . Of the 22 % ( 35 of 160 ) of patients with lymph node involvement , 16 % ( 25 of 160 ) had at least 1 macrometastasis , and 6 % ( 10 of 160 ) had at least a micrometastasis . Another 2.5 % ( 4 of 160 ) had isolated tumor cells . Of 404 lymph nodes removed , 297 ( 74 % ) were true sentinel nodes . The lymph node retrieval rate was 2.5 nodes per patient overall , 1.9 nodes per patient with the st and ard technique , and 2.0 nodes per patient with the magnetic technique . Conclusions The magnetic technique is a feasible technique for SLNB , with an identification rate that is not inferior to the st and ard technique BACKGROUND The goals of axillary-lymph-node dissection ( ALND ) are to maximise survival , provide regional control , and stage the patient . However , this technique has substantial side-effects . The purpose of the B-32 trial is to establish whether sentinel-lymph-node ( SLN ) resection can achieve the same therapeutic goals as conventional ALND but with decreased side-effects . The aim of this paper is to report the technical success and accuracy of SLN resection plus ALND versus SLN resection alone . METHODS 5611 women with invasive breast cancer were r and omly assigned to receive either SLN resection followed by immediate conventional ALND ( n=2807 ; group 1 ) or SLN resection without ALND if SLNs were negative on intraoperative cytology and histological examination ( n=2804 ; group 2 ) in the B-32 trial . Patients in group 2 underwent ALND if no SLNs were identified or if one or more SLNs were positive on intraoperative cytology or subsequent histological examination . Primary endpoints , including survival , regional control , and morbidity , will be reported later . Secondary endpoints are accuracy and technical success and are reported here . This trial is registered with the Clinical Trial registry , number NCT00003830 . FINDINGS Data for technical success were available for 5536 of 5611 patients ; 75 declined protocol treatment , had no SLNs removed , or had no SLN resection done . SLNs were successfully removed in 97.2 % of patients ( 5379 of 5536 ) in both groups combined . Identification of a preincision hot spot was associated with greater SLN removal ( 98.9 % [ 5072 of 5128 ] ) . Only 1.4 % ( 189 of 13171 ) of SLN specimens were outside of axillary levels I and II . 65.1 % ( 8571 of 13 171 ) of SLN specimens were both radioactive and blue ; a small percentage was identified by palpation only ( 3.9 % [ 515 of 13 171 ] ) . The overall accuracy of SLN resection in patients in group 1 was 97.1 % ( 2544 of 2619 ; 95 % CI 96.4 - 97.7 ) , with a false-negative rate of 9.8 % ( 75 of 766 ; 95 % CI 7.8 - 12.2 ) . Differences in tumour location , type of biopsy , and number of SLNs removed significantly affected the false-negative rate . Allergic reactions related to blue dye occurred in 0.7 % ( 37 of 5588 ) of patients with data on toxic effects . INTERPRETATION The findings reported here indicate excellent balance in clinical patient characteristics between the two r and omised groups and that the success of SLN resection was high . These findings are important because the B-32 trial is the only trial of sufficient size to provide definitive information related to the primary outcome measures of survival and regional control . Removal of more than one SLN and avoidance of excisional biopsy are important variables in reducing the false-negative rate |
12,999 | 19,413,706 | We posit , based on the experimental evidence , that calculating the energy density of diets by excluding drinks and including calories from drinks as a covariate in the analysis is the most valid and reliable method of testing the relationship between energy density and weight gain in free-living humans . | The association between dietary energy density , increased energy intake and weight gain is supported by experimental evidence , but confirmation of an effect in free-living humans is limited .
Experimental evidence supports a role of energy density in obesity through changes in food composition , not drinks consumption .
The inclusion of drinks in the calculation creates a variable of question able validity and has a substantive impact on the estimated energy density of the diet . | The energy density ( ED ; kcal/g ) of an entrée influences children 's energy intake ( EI ) , but the effect of simultaneously changing both ED and portion size of an entrée on preschool children 's EI is unknown . In this within-subject crossover study , 3- to 5-year-old children ( 30 boys , 31 girls ) in a daycare facility were served a test lunch once/week for 4 weeks . The amount and type of vegetables and cheeses incorporated into the sauce of a pasta entrée were manipulated to create two versions that varied in ED by 25 % ( 1.6 or 1.2 kcal/g ) . Across the weeks , each version of the entrée was served to the children in each of two portion sizes ( 400 or 300 g ) . Lunch , consumed ad libitum , also included carrots , applesauce , and milk . Decreasing ED of the entrée by 25 % significantly ( P<0.0001 ) reduced children 's EI of the entrée by 25 % ( 63.1+/-8.3 kcal ) and EI at lunch by 17 % ( 60.7+/-8.9 kcal ) . Increasing the proportion of vegetables in the pasta entrée increased children 's vegetable intake at lunch by half of a serving of vegetables ( P<0.01 ) . Decreasing portion size of the entrée by 25 % did not significantly affect children 's total food intake or EI at lunch . Therefore , reducing the ED of a lunch entrée result ed in a reduction in children 's EI from the entrée and from the meal in both portion size conditions . Decreasing ED by incorporating more vegetables into recipes is an effective way of reducing children 's EI while increasing their vegetable intake BACKGROUND The results of previous studies indicated that energy density , independent of fat content , influences energy intake . In most studies , however , both fat content and energy density were lower than in typical American diets . OBJECTIVE We examined the influence of energy density on intake when fat content was above , below , or similar to the amount of fat typically consumed and when energy density was closer to that of American diets . DESIGN Lean ( n = 19 ) and obese ( n = 17 ) women consumed all meals daily in our laboratory during 6 experimental sessions . The main entrées , consumed ad libitum , were formulated to vary in fat content ( 25 % , 35 % , and 45 % of energy ) and energy density ( 5.23 kJ/g , or low energy density , and 7.32 kJ/g , or high energy density ) but to have similar palatability . RESULTS Energy density influenced energy intake across all fat contents in both lean and obese women ( P < 0.0001 ) . Women consumed less energy in the low ( 7531 kJ ) than in the high ( 9414 kJ ) energy density condition . Despite this 20 % lower energy intake , there were only small differences in hunger ( 7 % ) and fullness ( 5 % ) . Women consumed a similar volume , but not weight , of food daily across conditions . Differences in intake by weight , but not volume , occurred because for some versions of manipulated foods , weight and volume were not directly proportional . CONCLUSIONS Energy density affected energy intake across different fat contents and at levels of energy density comparable with those in typical diets . Furthermore , our findings suggest that cues related to the amount of food consumed have a greater influence on short-term intake than does the amount of energy consumed BACKGROUND The contribution of energy density ( ED ) of the total diet to increased risk of obesity from childhood into adolescence is unclear . OBJECTIVE We assessed the relation between the ED of the diet in childhood , calculated in a number of ways , and change in adiposity from childhood to adolescence . DESIGN In a prospect i ve study , 48 children ( 30 boys , 18 girls ) were initially studied at age 6 - 8 y ( baseline ) and followed up at age 13 - 17 y. Daily ED , energy intake , and food intake were assessed at baseline by 7-d weighed food records concurrent with estimates of total energy expenditure ( TEE ) by doubly labeled water . ED was calculated with the use of 5 published methods . Obesity risk was defined with the use of body fat from total body water by isotope dilution . Body fat was normalized for height and expressed as fat mass index ( FMI ) . Change in adiposity was calculated as follow-up FMI minus baseline FMI . RESULTS Misreporting of energy intake at the group level at baseline was low relative to the TEE . ED of the total diet at baseline by the 3 methods for calculating ED that excluded all or most beverages was prospect ively associated with change in FMI . However , ED of the total diet by any of the methods was not associated with change in the percentage body fat , body mass index , or waist circumference z scores . CONCLUSION The methods used to calculate ED and to assess obesity risk lead to different conclusions about the relation between the ED of the diet in childhood and gain in fat into adolescence BACKGROUND Consuming foods low in energy density ( kcal/g ) decreases energy intake over several days , but the effectiveness of this strategy for weight loss has not been tested . OBJECTIVE The effects on weight loss of 2 strategies for reducing the energy density of the diet were compared over 1 y. DESIGN Obese women ( n = 97 ) were r and omly assigned to groups counseled either to reduce their fat intake ( RF group ) or to reduce their fat intake and increase their intake of water-rich foods , particularly fruit and vegetables ( RF+FV group ) . No goals for energy or fat intake were assigned ; the subjects were instructed to eat ad libitum amounts of food while following the principles of their diet . RESULTS After 1 y , study completers ( n = 71 ) in both groups had significant decreases in body weight ( P < 0.0001 ) . Subjects in the RF+FV group , however , had a significantly different pattern of weight loss ( P = 0.002 ) than did subjects in the RF group . After 1 y , the RF+FV group lost 7.9 + /- 0.9 kg and the RF group lost 6.4 + /- 0.9 kg . Analysis of all r and omly assigned subjects also showed a different pattern of weight loss between groups ( P = 0.021 ) . Diet records indicated that both groups had similar reductions in fat intake . The RF+FV group , however , had a lower dietary energy density than did the RF group ( P = 0.019 ) as the result of consuming a greater weight of food ( P = 0.025 ) , especially fruit and vegetables ( P = 0.037 ) . The RF+FV group also reported less hunger ( P = 0.003 ) . CONCLUSION Reducing dietary energy density , particularly by combining increased fruit and vegetable intakes with decreased fat intake , is an effective strategy for managing body weight while controlling hunger BACKGROUND Dietary energy density ( ED ) reductions are associated with energy intake ( EI ) reductions . Little is known about influences on body weight ( BW ) . OBJECTIVES We examined the effects of behavioral interventions on ED values and explored how 6-mo ED changes relate to BW . DESIGN Prehypertensive and hypertensive persons were r and omly assigned to 1 of 3 groups : the established group received an 18-session intervention implementing well-established hypertension recommendations ( eg , weight loss , sodium reduction , and physical activity ) , the established+Dietary Approaches to Stop Hypertension ( DASH ) group received an 18-session intervention also implementing the DASH diet , and the advice group received 1 session on these topics . Two 24-h dietary recalls were collected ( n=658 ) . RESULTS Each group had significant declines in EI , ED , and BW . The established and established+DASH groups had the greatest EI and BW reductions . The established+DASH group had the greatest ED reduction and the greatest increase in the weight of food consumed . When groups were combined and analyzed by ED change tertiles , participants in the highest tertile ( ie , largest ED reduction ) lost more weight ( 5.9 kg ) than did those in the middle ( 4.0 kg ) or lowest ( 2.4 kg ) tertile . Participants in the highest and middle tertiles increased the weight of food they consumed ( 300 and 80 g/d , respectively ) but decreased their EI ( 500 and 250 kcal/d ) . Conversely , those in the lowest tertile decreased the weight of food consumed ( 100 g/d ) , with little change in EI . The highest and middle tertiles had favorable changes in fruit , vegetable , vitamin , and mineral intakes . CONCLUSION Both large and modest ED reductions were associated with weight loss and improved diet quality To examine whether artificial sweeteners aid in the control of long-term food intake and body weight , we gave free-living , normal-weight subjects 1150 g soda sweetened with aspartame ( APM ) or high-fructose corn syrup ( HFCS ) per day . Relative to when no soda was given , drinking APM-sweetened soda for 3 wk significantly reduced calorie intake of both females ( n = 9 ) and males ( n = 21 ) and decreased the body weight of males but not of females . However , drinking HFCS-sweetened soda for 3 wk significantly increased the calorie intake and body weight of both sexes . Ingesting either type of soda reduced intake of sugar from the diet without affecting intake of other nutrients . Drinking large volumes of APM-sweetened soda , in contrast to drinking HFCS-sweetened soda , reduces sugar intake and thus may facilitate the control of calorie intake and body weight BACKGROUND Little is known about the long-term effects of dietary energy density ( ED ) on weight gain . OBJECTIVE The objective was to assess the long-term relation between changes in dietary ED and age-related weight gain . DESIGN We conducted a prospect i ve study of 50 026 women ( x + /- SD age : 36.5 + /- 4.6 y ) in the Nurses ' Health Study II followed from 1991 to 1999 . Dietary ED and body weight were ascertained in 1991 , 1995 , and 1999 . Total dietary ED was calculated by dividing each subject 's daily energy intake ( kcal ) by the reported weight ( g ) of all foods consumed . RESULTS Dietary ED was positively correlated with saturated fat ( r = 0.16 ) , trans fat ( r = 0.15 ) , and the glycemic index ( r = 0.16 ) , but was inversely correlated with vegetable protein ( r = -0.30 ) , vegetables ( r = -0.27 ) , and fruit ( r = -0.17 ) . ED was not significantly correlated with total fat intake as a percentage of energy ( r = 0.08 ) . Women who increased their dietary ED during follow-up the most ( 5th quintile ) had a significantly greater multivariate-adjusted weight gain than did those who decreased their dietary ED ( 1st quintile ) ( 8-y time period : 6.42 kg compared with 4.57 kg ; P for trend < 0.001 ) . However , the amount of weight change over time varied considerably according to the ED values of individual foods and beverages . CONCLUSION A high dietary ED reflects a dietary pattern higher in saturated and trans fats and refined carbohydrates . Increases in dietary ED were associated with greater weight gain among middle-aged women during 8 y of follow-up . However , public health recommendations can not be made simply on the basis of ED values of individual foods and beverages We previously increased the energy density and fat content across three diets ( factorial design ) , which led to a marked increase in energy intake in six men over 7 d while continuously resident in a whole-body indirect calorimeter . In the present study we fed the same diets to seven men who were resident in , but not confined to , a metabolic suite for 2 wk/diet . This added a component of increased physical activity . The fat , carbohydrate , and protein contents , respectively , of each diet ( as a percent of energy ) were as follows : low-fat ( LF ) , 20:67:13 ; medium-fat ( MF ) , 40:47:13 ; and high-fat ( HF ) , 60:27:13 . Energy density increased as the percent of fat in the diet increased . Energy intakes from the LF , MF , and HF diets ( 9.11 , 10.32 , and 12.78 MJ/d , respectively ) were almost identical to those in our calorimeter study ( 9.02 , 10.2 , and 12.35 MJ/d , respectively ) whereas energy expenditures ( estimated by the doubly labeled water method ) were 12.45 , 12.10 , and 11.97 MJ/d on the LF , MF and HF diets , respectively , compared with 9.48 , 9.53 , and 9.78 MJ/d , respectively , in our calorimeter study . This finding suggests that diet composition and energy expenditure combined influence energy balance in humans BACKGROUND The rising prevalence of obesity in children has been linked in part to the consumption of sugar-sweetened drinks . Our aim was to examine this relation . METHODS We enrolled 548 ethnically diverse schoolchildren ( age 11.7 years , SD 0.8 ) from public schools in four Massachusetts communities , and studied them prospect ively for 19 months from October , 1995 , to May , 1997 . We examined the association between baseline and change in consumption of sugar-sweetened drinks ( the independent variables ) , and difference in measures of obesity , with linear and logistic regression analyses adjusted for potentially confounding variables and clustering of results within schools . FINDINGS For each additional serving of sugar-sweetened drink consumed , both body mass index ( BMI ) ( mean 0.24 kg/m2 ; 95 % CI 0.10 - 0.39 ; p=0.03 ) and frequency of obesity ( odds ratio 1.60 ; 95 % CI 1.14 - 2.24 ; p=0.02 ) increased after adjustment for anthropometric , demographic , dietary , and lifestyle variables . Baseline consumption of sugar-sweetened drinks was also independently associated with change in BMI ( mean 0.18 kg/m2 for each daily serving ; 95 % CI 0.09 - 0.27 ; p=0.02 ) . INTERPRETATION Consumption of sugar-sweetened drinks is associated with obesity in children Objective : To test if an adult Mediterranean population consumes different food volumes while spontaneously ingesting diets of different energy density and to estimate which are the food and nutritional profiles of these diets . Design : A cross-sectional study of food consumption . Setting : Faculty of Medicine and Health Sciences , Universitat Rovira i Virgili , Reus . Subjects : Five hundred and seventy two adult individuals ( 25–65 y ) r and omly selected from the population census of Reus . Intervention : 24 hour recall method for 3 non-consecutive days including one holiday . The population was classified into three groups of differing energy densities by simple linear regression analysis . Means were compared by ANOVA . Results : Both sexes consume similar food volumes across the different levels of energy density . High energy density consumers ingest significantly more red meat , olive oil , sweet cereals , cereals and sugars and less reduced fat milk , green vegetables and fruit compared to low energy density consumers . Male and female high energy density consumers show a significantly higher consumption of energy ( 1686 kJ and 2200 kJ , respectively ) ( P<0.001 ) , a 5.2 % ( P<0.001 ) and 2.3 % ( P<0.05 ) respectively higher energy intake derived from fat and a 1.3 % ( P<0.05 ) and 1.3 % ( P<0.05 ) respectively higher energy intake derived from saturated fatty acids compared to low energy density consumers . Conclusions : Our adult Mediterranean population normally consumes similar food volumes , independently of the energy density ingested . High energy dense diets in our population could represent an important health risk because they are excessively rich in energy , fats and saturated fatty acids . Sponsorship : City Council of Reus . European Journal of Clinical Nutrition ( 2000 ) 55 , BACKGROUND : Beverages are contributing an increased proportion of energy to the diet . Because they elicit a weak compensatory dietary response , they may increase risk of positive energy balance . OBJECTIVES : This study aim ed to document the differential effects of matched liquid and solid carbohydrate loads on diet and body weight . DESIGN : In a cross-over design , seven males and eight females consumed dietary carbohydrate loads of 1880 kJ/day as a liquid ( soda ) or solid ( jelly beans ) during two 4 week periods separated by a 4 week washout . Subjects were permitted to consume the loads however they chose . In addition to baseline measurements , diet records were obtained on r and om days throughout the study , body composition was measured weekly , physical activity was assessed before and after treatments and hunger was assessed during washout and midway through each treatment . RESULTS : Free-feeding energy intake during the solid period was significantly lower than intake prior to this period . Dietary energy compensation was precise ( 118 % ) . No decrease in free-feeding energy intake occurred during the liquid period . Total daily energy intake increased by an amount equal to the load result ing in dietary compensation of −17 % . Consequently , body weight and BMI increased significantly only during the liquid period . Physical activity and hunger were unchanged . CONCLUSIONS : This study indicates that liquid carbohydrate promotes positive energy balance , whereas a comparable solid carbohydrate elicits precise dietary compensation . Increased consumption of energy-yielding fluids may promote positive energy balance OBJECTIVE : This study examined the effects of covert alterations in the energy density ( ED ) of mixed , medium fat ( MF ) diets on ad libitum food and energy intake ( EI ) , subjective hunger and body weight in humans . DESIGN : R and omised cross-over design . Subjects were each studied three times ( factorial design ) , during 14 d , throughout which they had ad libitum access to one of three covertly-manipulated MF diets . SUBJECTS : Six healthy men , mean age (s.e.m.)=30.0 y ( 12.76 y ) , mean weight=71.67 kg ( 19.80 kg ) ; mean height=1.79 m ( 0.22 m ) , body mass index ( BMI ) = 22.36 ( 2.60 ) kg/m2 , were studied . The fat , carbohydrate ( CHO ) and protein in each diet ( as a proportion of the total energy ) and energy density ( ED ) were , low-ED ( LED ) , 38:49:13 % ; 373 kJ/100 g ; medium-ED ( MED ) , 40:47:13 % ; 549 kJ/100 g ; high-ED ( HED ) , 39:48:13 % ; 737 kJ/100 g. Subjects could alter the amount but not the composition of foods eaten . They were resident in ( but not confined to ) a metabolic suite throughout the study . RESULTS : Solid food intake decreased as ED increased , giving mean values of 2.84 , 2.51 and 2.31 kg/d , respectively . This was insufficient to defend energy balance , since energy intake increased with increasing ED ( F ( 2,10 ) 16.08 ; P<0.001 ) giving mean intakes of 10.12 , 12.80 and 16.17 MJ/d , respectively . Rated pleasantness of food ( measured on visual analogue scales ) was not significantly different between diets nor was subjective hunger different between the LED , MED and HED diets , respectively . Diet significantly affected body weight ( F (2,10)=4.62 ; P=0.038 ) , producing changes of −1.20 , + 0.02 and + 0.95 kg , respectively , by day 14 . CONCLUSION : Dietary ED can influence EI and body weight , since changes in amount eaten alone are insufficient to defend energy balance , when subjects feed on unfamiliar diets and diet selection is precluded . Comparison with our previous studies suggest that there was compensation in solid food intake when ED was altered using mixed diets ( as in this study ) compared to previous studies which primarily used fat or CHO to alter dietary ED OBJECTIVE The energy density ( kilocalories per gram ) of foods influences short-term energy intake . This 1-year clinical trial tested the effect on weight loss of a diet incorporating one or two servings per day of foods equal in energy but differing in energy density . RESEARCH METHODS AND PROCEDURES Dietitians instructed 200 overweight and obese women and men to follow an exchange-based energy-restricted diet . Additionally , subjects were r and omized to consume daily either one or two servings of low energy-dense soup , two servings of high energy-dense snack foods , or no special food ( comparison group ) . RESULTS All four groups showed significant weight loss at 6 months that was well maintained at 12 months . The magnitude of weight loss , however , differed by group ( p=0.006 ) . At 1 year , weight loss in the comparison ( 8.1+/-1.1 kg ) and two-soup ( 7.2+/-0.9 kg ) groups was significantly greater than that in the two-snack group ( 4.8+/-0.7 kg ) ; weight loss in the one-soup group ( 6.1+/-1.1 kg ) did not differ significantly from other groups . Weight loss was significantly correlated with the decrease in dietary energy density from baseline at 1 and 2 months ( p=0.0001 ) but not at 6 and 12 months . DISCUSSION On an energy-restricted diet , consuming two servings of low energy-dense soup daily led to 50 % greater weight loss than consuming the same amount of energy as high energy-dense snack food . Regularly consuming foods that are low in energy density can be an effective strategy for weight management Objective : To assess the changes in energy intake ( EI ) , food intake volume ( FV ) and energy density ( ED ) related to age and gender in a population in the Mediterranean area of Spain , and to determine the different role of FV and ED on the consecution of the adequate EI throughout lifespan . Subjects : One thous and and eighty-eight individuals ( 1–65 y ) r and omly selected from the population census . Design : Cross-sectional study in which food intake was quantified by 24 h dietary recall , three non-consecutive days . Height and weight measurements were taken in 885 individuals . Results : EI , FV and ED increased progressively ( P<0.001 ) between 1–2 y and 10–12 y of age in both sexes . At 1–2 y the EI is 5.8±1.5 MJ/d , FV 1195±275 g/d and ED 4.8±0.9 kJ/g . Between 1–2 and 3–4 y , coinciding with an EI that increased up to 7.2±1.5 MJ/d , there was an increase in ED up to 6.1±0.8 kJ/g ( P<0.001 ) , while the FV did not vary significantly . At the start of puberty , between 7–9 and 10–12 y , when the EI increased to 9.7±0.9 MJ/d ( P<0.001 ) in males , the ED rose to 7.1±0.9 kJ/g ( P<0.001 ) while the FV did not vary significantly . At this age , a significant difference between the genders was observed in the EI ( P=0.04 ) , and in the ED ( P=0.02 ) but not , as yet , in the FV . During adulthood , a significant trend towards decrease ( P<0.001 in both sexes ) was observed in EI and ED . However , FV decreased significantly only in females . Conclusions : The changes in energy intake that were observed with respect to age and gender were accommo date d-for by changes in the ED of the diet rather than by variations in food volume intake . Auto-regulation of the ED of the diet , sufficient for energy intake requirement changes , appears to be an essential human capacity for efficient nutrition . Sponsorship : This study was funded , in part , by a grant for B Vizmanos from DANONE , Spain OBJECTIVE We examined whether associations between dietary components and , in particular , energy density ( ED ) predicted subsequent 5-year weight changes . RESEARCH METHODS AND PROCEDURES The present longitudinal population study was part of the Danish World Health Organization Multinational Monitoring of Trends and Determinants in Cardiovascular Disease ( MONICA ) and the 1936 cohort dietary studies . Effects of components were studied in relation to subsequent 5-year weight changes in 862 men and 900 women , 30 to 60 years old . Linear multiple regression analyses were conducted . RESULTS Mean 5-year changes in body weight ( BW ) were 1.2 + /- 3.9 and 1.3 + /- 4.6 kg for men and women , respectively . In general , neither ED nor any of the dietary components was associated with subsequent change in BW . In women , ED was positively associated with weight gain among the obese ( BMI > 30 kg/m2 ) and inversely associated with weight gain in normal-weight women ( BMI < 25 kg/m2 ) ( p = 0.01 ) . However , in men there was a non-significant inverse trend between ED and weight gain in the obese and no significant interaction . DISCUSSION To our knowledge , this is the first prospect i ve study to examine the associations between ED and subsequent changes in BW , and despite a general belief that ED is a major determinant of obesity , the present study did not generally lend support for an association . However , among certain subgroups , an energy-dense diet may be a risk factor for weight development OBJECTIVE The increase in consumption of sugar-added beverages over recent decades may be partly responsible for the obesity epidemic among U.S. adolescents . Our aim was to evaluate the relationship between BMI changes and intakes of sugar-added beverages , milk , fruit juices , and diet soda . RESEARCH METHODS AND PROCEDURES Our prospect i ve cohort study included > 10,000 boys and girls participating in the U.S. Growing Up Today Study . The participants were 9 to 14 years old in 1996 and completed question naires in 1996 , 1997 , and 1998 . We analyzed change in BMI ( kilograms per meter squared ) over two 1-year periods among children who completed annual food frequency question naires assessing typical past year intakes . We studied beverage intakes during the year corresponding to each BMI change , and in separate models , we studied 1-year changes in beverage intakes , adjusting for prior year intakes . Models included all beverages simultaneously ; further models adjusted for total energy intake . RESULTS Consumption of sugar-added beverages was associated with small BMI gains during the corresponding year ( boys : + 0.03 kg/m2 per daily serving , p = 0.04 ; girls : + 0.02 kg/m2 , p = 0.096 ) . In models not assuming a linear dose-response trend , girls who drank 1 serving/d of sugar-added beverages gained more weight ( + 0.068 , p = 0.02 ) than girls drinking none , as did girls drinking 2 servings/d ( + 0.09 , p = 0.06 ) or 3 + servings/d ( + 0.08 , p = 0.06 ) . Analyses of year-to-year change in beverage intakes provided generally similar findings ; boys who increased consumption of sugar-added beverages from the prior year experienced weight gain ( + 0.04 kg/m2 per additional daily serving , p = 0.01 ) . Children who increased intakes by 2 or more servings/d from the prior year gained weight ( boys : + 0.14 , p = 0.01 ; girls + 0.10 , p = 0.046 ) . Further adjusting our models for total energy intake substantially reduced the estimated effects , which were no longer significant . DISCUSSION Consumption of sugar-added beverages may contribute to weight gain among adolescents , probably due to their contribution to total energy intake , because adjustment for calories greatly attenuated the estimated associations Objective : This study compared 4-year changes in daily energy density ( ED ; kcal/g ) in children born at different risk for obesity , characterized the stability of ED and examined associations between ED and child body composition . Design : Prospect i ve cohort study to measure habitual dietary ED of children who are born at different risk for obesity . Subjects : Children who were born at high risk ( n=22 ) or low risk ( n=27 ) for obesity based on maternal pre-pregnancy weight . Measurements : Three-day food records were collected from children 's mothers at child ages 3 , 4 , 5 and 6 years . Three categories of ED were computed ( food only , food and milk , and food and all beverages ) and body composition assessed at each year . Results : The mean ( ±s.e.m . ) ED increased over time across all children ( linear trend : P<0.003 ) : 2.18±0.07 to 2.32±0.06 kcal/g ( food only ) ; 1.66±0.07 to 1.82±0.06 kcal/g ( food and milk ) ; and 1.24±0.04 to 1.37±0.05 kcal/g ( food and all beverages ) . Intraindividual coefficients of variation were smaller than those previously reported for adults . Weight indices were not correlated with dietary ED ( P>0.05 ) . Conclusion : Dietary ED increased in young children , irrespective of their predisposition to obesity , between the ages of 3 and 6 years . The genes that promote childhood obesity may not exert their influence through dietary ED , which may be more strongly influenced by environmental factors |
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